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Viruses, Volume 15, Issue 1 (January 2023) – 259 articles

Cover Story (view full-size image): Several arenaviruses, including Lassa virus (LASV) and Junin virus (JUNV), cause severe hemorrhagic fever with accompanying high fatality rates. Ribavirin, which is the drug of choice available for decades, loses effectiveness in advanced infections and is associated with serious side effects. We screened for novel therapeutic agents using an LASV minigenome (MG) system. We identified topoisomerase II (TOP2) inhibitors as potent inhibitors of LASV, JUNV, and lymphocytic choriomeningitis virus (LCMV) MG systems. They also efficiently limited the replication of LCMV and JUNV. Furthermore, TOP2 knockdown restricted JUNV replication. Our results suggest that TOP2 plays an important role in arenavirus replication and reveals the potential of TOP2 as an efficient novel anti-panarenaviral target. View this paper
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3 pages, 178 KiB  
Editorial
Special Issue “New Frontiers in Small DNA Virus Research”
by Katerina Strati and Dohun Pyeon
Viruses 2023, 15(1), 259; https://doi.org/10.3390/v15010259 - 16 Jan 2023
Viewed by 1386
Abstract
Scientific progress in understanding, preventing, treating, and managing viral infections and associated diseases exemplifies the extent to which research on small DNA tumor viruses has impacted human health [...] Full article
(This article belongs to the Special Issue New Frontiers in Small DNA Virus Research)
13 pages, 1977 KiB  
Article
A Conserved Stem-Loop Structure within ORF5 Is a Frequent Recombination Hotspot for Porcine Reproductive and Respiratory Syndrome Virus 1 (PRRSV-1) with a Particular Modified Live Virus (MLV) Strain
by Marlene Mötz, Julia Stadler, Heinrich Kreutzmann, Andrea Ladinig, Benjamin Lamp, Angelika Auer, Christiane Riedel and Till Rümenapf
Viruses 2023, 15(1), 258; https://doi.org/10.3390/v15010258 - 16 Jan 2023
Cited by 3 | Viewed by 2261
Abstract
The emergence of recombinant PRRSV strains has been observed for more than a decade. These recombinant viruses are characterized by a genome that contains genetic material from at least two different parental strains. Due to the advanced sequencing techniques and a growing number [...] Read more.
The emergence of recombinant PRRSV strains has been observed for more than a decade. These recombinant viruses are characterized by a genome that contains genetic material from at least two different parental strains. Due to the advanced sequencing techniques and a growing number of data bank entries, the role of PRRSV recombinants has become increasingly important since they are sometimes associated with clinical outbreaks. Chimeric viruses observed more recently are products of PRRSV wild-type and vaccine strains. Here, we report on three PRRSV-1 isolates from geographically distant farms with differing clinical manifestations. A sequencing and recombination analysis revealed that these strains are crossovers between different wild-type strains and the same modified live virus vaccine strain. Interestingly, the recombination breakpoint of all analyzed isolates appears at the beginning of open reading frame 5 (ORF5). RNA structure predictions indicate a conserved stem loop in close proximity to the recombination hotspot, which is a plausible cause of a polymerase template switch during RNA replication. Further research into the mechanisms of the stem loop is needed to help understand the PRRSV recombination process and the role of MLVs as parental strains. Full article
(This article belongs to the Special Issue State-of-the-Art Virology Research in Austria)
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9 pages, 246 KiB  
Communication
Intravenous Infection of Small Ruminants Suggests a Goat-Restricted Host Tropism and Weak Humoral Immune Response for an Atypical Bluetongue Virus Isolate
by Massimo Spedicato, Giovanni Di Teodoro, Liana Teodori, Mariangela Iorio, Alessandra Leone, Barbara Bonfini, Lilia Testa, Maura Pisciella, Claudia Casaccia, Ottavio Portanti, Emanuela Rossi, Tiziana Di Febo, Nicola Ferri, Giovanni Savini and Alessio Lorusso
Viruses 2023, 15(1), 257; https://doi.org/10.3390/v15010257 - 16 Jan 2023
Viewed by 1590
Abstract
Bluetongue virus (BTV) is the etiologic agent of bluetongue (BT), a viral WOAH-listed disease affecting wild and domestic ruminants, primarily sheep. The outermost capsid protein VP2, encoded by S2, is the virion’s most variable protein, and the ability of reference sera to neutralize [...] Read more.
Bluetongue virus (BTV) is the etiologic agent of bluetongue (BT), a viral WOAH-listed disease affecting wild and domestic ruminants, primarily sheep. The outermost capsid protein VP2, encoded by S2, is the virion’s most variable protein, and the ability of reference sera to neutralize an isolate has so far dictated the differentiation of 24 classical BTV serotypes. Since 2008, additional novel BTV serotypes, often referred to as “atypical” BTVs, have been documented and, currently, the full list includes 36 putative serotypes. In March 2015, a novel atypical BTV strain was detected in the blood of asymptomatic goats in Sardinia (Italy) and named BTV-X ITL2015. The strain re-emerged in the same region in 2021 (BTV-X ITL2021). In this study, we investigated the pathogenicity and kinetics of infection of BTV-X ITL2021 following subcutaneous and intravenous infection of small ruminants. We demonstrated that, in our experimental settings, BTV-X ITL2021 induced a long-lasting viraemia only when administered by the intravenous route in goats, though the animals remained healthy and, apparently, did not develop a neutralizing immune response. Sheep were shown to be refractory to the infection by either route. Our findings suggest a restricted host tropism of BTV-X and point out goats as reservoirs for this virus in the field. Full article
(This article belongs to the Section Animal Viruses)
13 pages, 663 KiB  
Article
Subjective and Objective Cognitive Impairments in Non-Hospitalized Persons 9 Months after SARS-CoV-2 Infection
by Inge Kirchberger, Daniela Peilstöcker, Tobias D. Warm, Jakob Linseisen, Alexander Hyhlik-Dürr, Christine Meisinger and Yvonne Goßlau
Viruses 2023, 15(1), 256; https://doi.org/10.3390/v15010256 - 16 Jan 2023
Cited by 8 | Viewed by 3494
Abstract
Studies on cognitive problems of persons with mild COVID-19 courses are still lacking. This study aimed to determine the frequency and associated factors of subjective and objective cognitive problems after COVID-19 in non-hospitalized persons. Study participants were examined at the University Hospital of [...] Read more.
Studies on cognitive problems of persons with mild COVID-19 courses are still lacking. This study aimed to determine the frequency and associated factors of subjective and objective cognitive problems after COVID-19 in non-hospitalized persons. Study participants were examined at the University Hospital of Augsburg from 04/11/2020 to 26/05/2021. The Wechsler Adult Intelligence Scale (WAIS) IV digit span, Stroop Color and Word Test (SCWT), Regensburger verbal fluency test (RWT) and, subjective ratings of memory and concentration were applied. Of the 372 participants (mean age 46.8 ± 15.2 years, 54.3% women, median time after infection 9.1 months), 24.9% reported concentration and 21.9% memory problems. Overall, 55.6% of the participants had at least a mild negative alteration in any cognitive test. The strongest impairments were found regarding memory functions (41.1% mild alterations, 6.2% distinct impairments) and verbal fluency (12.4% mild alterations, 5.4% distinct impairments). SCWT showed negative alterations in no more than 3.0% of the participants. Level of school education, age, and depressiveness emerged as significantly related to the cognitive tests. The number of complaints and depressiveness were significantly associated with subjective memory and concentration problems. It is important to identify mild cognitive impairment in non-hospitalized COVID-19 patients early to offer them effective interventions. Full article
(This article belongs to the Special Issue Post-COVID Syndrome)
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21 pages, 2933 KiB  
Article
Equine Arteritis Virus in Monocytic Cells Suppresses Differentiation and Function of Dendritic Cells
by Nathifa A. Moyo, Dave Westcott, Rachel Simmonds and Falko Steinbach
Viruses 2023, 15(1), 255; https://doi.org/10.3390/v15010255 - 16 Jan 2023
Viewed by 1713
Abstract
Equine viral arteritis is an infectious disease of equids caused by equine arteritis virus (EAV), an RNA virus of the family Arteriviridae. Dendritic cells (DC) are important modulators of the immune response with the ability to present antigen to naïve T cells and [...] Read more.
Equine viral arteritis is an infectious disease of equids caused by equine arteritis virus (EAV), an RNA virus of the family Arteriviridae. Dendritic cells (DC) are important modulators of the immune response with the ability to present antigen to naïve T cells and can be generated in vitro from monocytes (MoDC). DC are important targets for many viruses and this interaction is crucial for the establishment—or rather not—of an anti-viral immunity. Little is known of the effect EAV has on host immune cells, particularly DC. To study the interaction of eqDC with EAV in vitro, an optimized eqMoDC system was used, which was established in a previous study. MoDC were infected with strains of different genotypes and pathogenicity. Virus replication was determined through titration and qPCR. The effect of the virus on morphology, phenotype and function of cells was assessed using light microscopy, flow cytometry and in vitro assays. This study confirms that EAV replicates in monocytes and MoDC. The replication was most efficient in mature MoDC, but variable between strains. Only the virulent strain caused a significant down-regulation of certain proteins such as CD14 and CD163 on monocytes and of CD83 on mature MoDC. Functional studies conducted after infection showed that EAV inhibited the endocytic and phagocytic capacity of Mo and mature MoDC with minimal effect on immature MoDC. Infected MoDC showed a reduced ability to stimulate T cells. Ultimately, EAV replication resulted in an apoptosis-mediated cell death. Thus, EAV evades the host anti-viral immunity both by inhibition of antigen presentation early after infection and through killing infected DC during replication. Full article
(This article belongs to the Special Issue Viral Cycle and Cell Host Interactions of Equine Viruses)
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35 pages, 1378 KiB  
Systematic Review
A Systematic Review of Mathematical Models of Dengue Transmission and Vector Control: 2010–2020
by Samson T. Ogunlade, Michael T. Meehan, Adeshina I. Adekunle and Emma S. McBryde
Viruses 2023, 15(1), 254; https://doi.org/10.3390/v15010254 - 16 Jan 2023
Cited by 8 | Viewed by 3833
Abstract
Vector control methods are considered effective in averting dengue transmission. However, several factors may modify their impact. Of these controls, chemical methods, in the long run, may increase mosquitoes’ resistance to chemicides, thereby decreasing control efficacy. The biological methods, which may be self-sustaining [...] Read more.
Vector control methods are considered effective in averting dengue transmission. However, several factors may modify their impact. Of these controls, chemical methods, in the long run, may increase mosquitoes’ resistance to chemicides, thereby decreasing control efficacy. The biological methods, which may be self-sustaining and very effective, could be hampered by seasonality or heatwaves (resulting in, e.g., loss of Wolbachia infection). The environmental methods that could be more effective than the chemical methods are under-investigated. In this study, a systematic review is conducted to explore the present understanding of the effectiveness of vector control approaches via dengue transmission models. Full article
(This article belongs to the Special Issue Mosquito-Borne Virus Ecology 2.0)
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13 pages, 1675 KiB  
Article
Reduced Neutralization Efficacy against Omicron Variant after Third Boost of BNT162b2 Vaccine among Liver Transplant Recipients
by Yana Davidov, Victoria Indenbaum, Michal Mandelboim, Keren Asraf, Tal Gonen, Keren Tsaraf, Oranit Cohen-Ezra, Mariya Likhter, Ital Nemet, Limor Kliker, Orna Mor, Ram Doolman, Carmit Cohen, Arnon Afek, Yitshak Kreiss, Gili Regev-Yochay, Yaniv Lustig and Ziv Ben-Ari
Viruses 2023, 15(1), 253; https://doi.org/10.3390/v15010253 - 16 Jan 2023
Cited by 2 | Viewed by 1505
Abstract
The immune responses of liver transplant (LT) recipients after the third boost of the BNT162b2mRNA vaccine improved. This study evaluates the durability of the immune response of LT recipients after the third boost, its predictors, and the impact of emerging variants. The receptor-binding [...] Read more.
The immune responses of liver transplant (LT) recipients after the third boost of the BNT162b2mRNA vaccine improved. This study evaluates the durability of the immune response of LT recipients after the third boost, its predictors, and the impact of emerging variants. The receptor-binding domain IgG was determined at median times of 22 (first test) and 133 days (second test) after the administration of the third boost. IgG antibody titers > 21.4 BAU/mL were defined as a positive response. The neutralization efficacies of the vaccine against the wild-type, Omicron, and Delta variants were compared in the first test. The 59 LT recipients were of a median age of 61 years (range 25–82); 53.5% were male. Following administration of the third dose, the positive immune response decreased from 81.4% to 76.3% between the first and second tests, respectively, (p < 0.0001). The multivariate analysis identified CNI monotherapy (p = 0.02) and hemoglobin > 12 g/dL (p = 0.02) as independent predictors of a maintained positive immune response 133 days after the third dose. The geometric mean titers of Omicron neutralization were significantly lower than the wild-type and Delta virus (21, 137, 128, respectively; p < 0.0001). The immune response after the third BNT162b2mRNA vaccine dose decreased significantly in LT recipients. Further studies are required to evaluate the efficacy of the fourth vaccine dose and the durability of the immune response. Full article
(This article belongs to the Section SARS-CoV-2 and COVID-19)
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11 pages, 1171 KiB  
Article
Direct-Acting Antivirals Reduce the De Novo Development of Esophageal Varices in Patients with Hepatitis C Virus Related Liver Cirrhosis
by Yung-Yu Hsieh, Wei-Ming Chen, Kao-Chi Chang, Te-Sheng Chang, Chao-Hung Hung, Yao-Hsu Yang, Shui-Yi Tung, Kuo-Liang Wei, Chen-Heng Shen, Cheng-Shyong Wu, Yuan-Jie Ding, Jing-Hong Hu, Yu-Ting Huang, Meng-Hung Lin, Chung-Kuang Lu, Yi-Hsiung Lin and Ming-Shyan Lin
Viruses 2023, 15(1), 252; https://doi.org/10.3390/v15010252 - 16 Jan 2023
Cited by 1 | Viewed by 1988
Abstract
The real-world benefits of direct-acting antiviral (DAA)-induced sustained virologic response (SVR) on the de novo occurrence and progression of esophageal varices (EV) remain unclear in patients with hepatitis C virus (HCV)-related liver cirrhosis (LC). This is a retrospective cohort study evaluating all patients [...] Read more.
The real-world benefits of direct-acting antiviral (DAA)-induced sustained virologic response (SVR) on the de novo occurrence and progression of esophageal varices (EV) remain unclear in patients with hepatitis C virus (HCV)-related liver cirrhosis (LC). This is a retrospective cohort study evaluating all patients with Child-Pugh class A HCV-related LC during 2013 to 2020 in the Chang Gung Medical System. A total of 215 patients fit the inclusion criteria and were enrolled. Of them, 132 (61.4%) patients achieved DAA induced-SVR and 83 (38.6%) did not receive anti-viral treatment. During a median follow-up of 18.4 (interquartile range, 10.1–30.9) months, the 2-year incidence of de novo EV occurrence was 8 (7.0%) in the SVR group and 7 (12.7%) in the treatment-naïve group. Compared to the treatment-naïve group, the SVR group was associated with a significantly lower incidence of EV occurrence (adjusted hazard ratio [aHR]: 0.47, p = 0.030) and a significantly lower incidence of EV progression (aHR: 0.55, p = 0.033). The risk of EV progression was strongly correlated with the presence of baseline EV (p < 0.001). To the best of our knowledge, this is the first study to demonstrate that DAA-induced SVR is associated with decreased risk of de novo EV occurrence and progression in the real world. Full article
(This article belongs to the Special Issue Viral Hepatitis Treatment 2.0)
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20 pages, 6416 KiB  
Article
Exploration of Microbially Derived Natural Compounds against Monkeypox Virus as Viral Core Cysteine Proteinase Inhibitors
by Amit Dubey, Maha M. Alawi, Thamir A. Alandijany, Isra M. Alsaady, Sarah A. Altwaim, Amaresh Kumar Sahoo, Vivek Dhar Dwivedi and Esam Ibraheem Azhar
Viruses 2023, 15(1), 251; https://doi.org/10.3390/v15010251 - 16 Jan 2023
Cited by 21 | Viewed by 2605
Abstract
Monkeypox virus (MPXV) is a member of the Orthopoxvirus genus and the Poxviridae family, which instigated a rising epidemic called monkeypox disease. Proteinases are majorly engaged in viral propagation by catalyzing the cleavage of precursor polyproteins. Therefore, proteinase is essential for monkeypox and [...] Read more.
Monkeypox virus (MPXV) is a member of the Orthopoxvirus genus and the Poxviridae family, which instigated a rising epidemic called monkeypox disease. Proteinases are majorly engaged in viral propagation by catalyzing the cleavage of precursor polyproteins. Therefore, proteinase is essential for monkeypox and a critical drug target. In this study, high-throughput virtual screening (HTVS) and molecular dynamics simulation were applied to detect the potential natural compounds against the proteinase of the monkeypox virus. Here, 32,552 natural products were screened, and the top five compounds were selected after implementing the HTVS and molecular docking protocols in series. Gallicynoic Acid F showed the minimum binding score of −10.56 kcal/mole in the extra precision scoring method, which reflected the highest binding with the protein. The top five compounds showed binding scores ≤−8.98 kcal/mole. These compound complexes were tested under 100 ns molecular dynamics simulation, and Vaccinol M showed the most stable and consistent RMSD trend in the range of 2 Å to 3 Å. Later, MM/GBSA binding free energy and principal component analysis were performed on the top five compounds to validate the stability of selected compound complexes. Moreover, the ligands Gallicynoic Acid F and H2-Erythro-Neopterin showed the lowest binding free energies of −61.42 kcal/mol and −61.09 kcal/mol, respectively. Compared to the native ligand TTP-6171 (ΔGBind = −53.86 kcal/mol), these two compounds showed preferable binding free energy, suggesting inhibitory application against MPXV proteinase. This study proposed natural molecules as a therapeutic solution to control monkeypox disease. Full article
(This article belongs to the Special Issue Innovative Inhibitors against Viral Targets)
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23 pages, 8849 KiB  
Article
Chetomin, a SARS-CoV-2 3C-like Protease (3CLpro) Inhibitor: In Silico Screening, Enzyme Docking, Molecular Dynamics and Pharmacokinetics Analysis
by Mahmoud A. A. Ibrahim, Alaa H. M. Abdelrahman, Dina E. M. Mohamed, Khlood A. A. Abdeljawaad, Mohamed Ahmed Naeem, Gamal A. Gabr, Ahmed M. Shawky, Mahmoud E. S. Soliman, Peter A. Sidhom, Paul W. Paré and Mohamed-Elamir F. Hegazy
Viruses 2023, 15(1), 250; https://doi.org/10.3390/v15010250 - 15 Jan 2023
Cited by 3 | Viewed by 2355
Abstract
The emergence of the Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to over 6 million deaths. The 3C-like protease (3CLpro) enzyme of the SARS-CoV-2 virus is an attractive druggable target for exploring therapeutic [...] Read more.
The emergence of the Coronavirus Disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to over 6 million deaths. The 3C-like protease (3CLpro) enzyme of the SARS-CoV-2 virus is an attractive druggable target for exploring therapeutic drug candidates to combat COVID-19 due to its key function in viral replication. Marine natural products (MNPs) have attracted considerable attention as alternative sources of antiviral drug candidates. In looking for potential 3CLpro inhibitors, the MNP database (>14,000 molecules) was virtually screened against 3CLpro with the assistance of molecular docking computations. The performance of AutoDock and OEDocking software in anticipating the ligand-3CLpro binding mode was first validated according to the available experimental data. Based on the docking scores, the most potent MNPs were further subjected to molecular dynamics (MD) simulations, and the binding affinities of those molecules were computed using the MM-GBSA approach. According to MM-GBSA//200 ns MD simulations, chetomin (UMHMNP1403367) exhibited a higher binding affinity against 3CLpro than XF7, with ΔGbinding values of −55.5 and −43.7 kcal/mol, respectively. The steadiness and tightness of chetomin with 3CLpro were evaluated, revealing the high stabilization of chetomin (UMHMNP1403367) inside the binding pocket of 3CLpro throughout 200 ns MD simulations. The physicochemical and pharmacokinetic features of chetomin were also predicted, and the oral bioavailability of chetomin was demonstrated. Furthermore, the potentiality of chetomin analogues –namely, chetomin A-D– as 3CLpro inhibitors was investigated. These results warrant further in vivo and in vitro assays of chetomin (UMHMNP1403367) as a promising anti-COVID-19 drug candidate. Full article
(This article belongs to the Special Issue Viral Enzyme Inhibitors: Structure and Dynamics)
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12 pages, 299 KiB  
Article
HIV-HCV Incidence in Low-Wage Agricultural Migrant Workers Living in Ghettos in Apulia Region, Italy: A Multicenter Cross Sectional Study
by Valentina Totaro, Giulia Patti, Francesco Vladimiro Segala, Renato Laforgia, Lucia Raho, Carmine Falanga, Marcella Schiavone, Luísa Frallonardo, Gianfranco Giorgio Panico, Vito Spada, Laura De Santis, Carmen Pellegrino, Roberta Papagni, Angelo D’Argenio, Roberta Novara, Claudia Marotta, Nicole Laforgia, Davide Fiore Bavaro, Giovanni Putoto, Annalisa Saracino and Francesco Di Gennaroadd Show full author list remove Hide full author list
Viruses 2023, 15(1), 249; https://doi.org/10.3390/v15010249 - 15 Jan 2023
Cited by 2 | Viewed by 1677
Abstract
Migrant populations are more susceptible to viral hepatitis and HIV due to the epidemiology from their country of origin or their social vulnerability when they arrive in Europe. The aims of the study are to explore the incidence of HIV and HCV in [...] Read more.
Migrant populations are more susceptible to viral hepatitis and HIV due to the epidemiology from their country of origin or their social vulnerability when they arrive in Europe. The aims of the study are to explore the incidence of HIV and HCV in low-wage agricultural migrant workers and their knowledge, attitude, and practice with regard to HIV and HCV, as well as their sexual behaviour and risk factors. As part of the mobile clinic services, we performed a screening campaign for HIV-HCV involving migrants living in three Apulian establishments. Results: Between January 2020 and April 2021, 309 migrants (n. 272, 88% male, mean age 28.5 years) were enrolled in the study. Most of the migrants interviewed (n = 297, 96%) reported a stopover in Libya during their trip to Italy. Only 0.9% (n. 3) of migrants reported having been tested for HCV, while 30.7% (n. 95) reported being tested for HIV. Furthermore, screening tests found four migrants (1.3%) to be HIV positive and nine (2.9%) to be HCV positive. The median knowledge score was 1 (IQR 0-3; maximum score: 6 points) for HCV and 3 (IQR 1-4; maximum score: 7 points) for HIV and low use of condoms was 5% (n. 16), while more than 95% show an attitude score of 5 (IQR 5-6; maximum score:6 points) on HIV-HCV education campaigns. In a multivariate analysis, being male (OR = 1.72; 95% CI 1.28–1.92), being single (OR = 1.63; 95% CI 1.20–2.03), being of low educational status (OR = 2.09; 95% CI 1.29–2.21), living in shantytowns for >12 months (OR = 1.95; 95% CI 1.25–2.55), and originating from the African continent (OR = 1.43; 95% CI 1.28–2.01) are significant predictors of poor knowledge on HCV. Our data show low knowledge, especially of HCV, confirming migrants as a population with a higher risk of infection. To develop education programmes, integrated care and screening among migrants could be an effective strategy, considering the high attitude toward these items shown in our study. Full article
(This article belongs to the Special Issue HIV and Co-infections: Updates and Insights)
18 pages, 3680 KiB  
Article
Humoral Immune Response Profile of COVID-19 Reveals Severity and Variant-Specific Epitopes: Lessons from SARS-CoV-2 Peptide Microarray
by Arup Acharjee, Arka Ray, Akanksha Salkar, Surbhi Bihani, Chaitanya Tuckley, Jayanthi Shastri, Sachee Agrawal, Siddhartha Duttagupta and Sanjeeva Srivastava
Viruses 2023, 15(1), 248; https://doi.org/10.3390/v15010248 - 15 Jan 2023
Cited by 5 | Viewed by 2687
Abstract
The amaranthine scale of the COVID-19 pandemic and unpredictable disease severity is of grave concern. Serological diagnostic aids are an excellent choice for clinicians for rapid and easy prognosis of the disease. To this end, we studied the humoral immune response to SARS-CoV-2 [...] Read more.
The amaranthine scale of the COVID-19 pandemic and unpredictable disease severity is of grave concern. Serological diagnostic aids are an excellent choice for clinicians for rapid and easy prognosis of the disease. To this end, we studied the humoral immune response to SARS-CoV-2 infection to map immunogenic regions in the SARS-CoV-2 proteome at amino acid resolution using a high-density SARS-CoV-2 proteome peptide microarray. The microarray has 4932 overlapping peptides printed in duplicates spanning the entire SARS-CoV-2 proteome. We found 204 and 676 immunogenic peptides against IgA and IgG, corresponding to 137 and 412 IgA and IgG epitopes, respectively. Of these, 6 and 307 epitopes could discriminate between disease severity. The emergence of variants has added to the complexity of the disease. Using the mutation panel available, we could detect 5 and 10 immunogenic peptides against IgA and IgG with mutations belonging to SAR-CoV-2 variants. The study revealed severity-based epitopes that could be presented as potential prognostic serological markers. Further, the mutant epitope immunogenicity could indicate the putative use of these markers for diagnosing variants responsible for the infection. Full article
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21 pages, 5129 KiB  
Article
Exploring the Expression and Function of cTyro3, a Candidate Zika Virus Receptor, in the Embryonic Chicken Brain and Inner Ear
by Vashi Negi, Richard J. Kuhn and Donna M. Fekete
Viruses 2023, 15(1), 247; https://doi.org/10.3390/v15010247 - 15 Jan 2023
Cited by 3 | Viewed by 1751
Abstract
The transmembrane protein Axl was proposed as an entry receptor for Zika virus (ZIKV) infection in vitro, but conflicting results from in vivo studies have made it difficult to establish Axl as a physiologically relevant ZIKV receptor. Both the functional redundancy of receptors [...] Read more.
The transmembrane protein Axl was proposed as an entry receptor for Zika virus (ZIKV) infection in vitro, but conflicting results from in vivo studies have made it difficult to establish Axl as a physiologically relevant ZIKV receptor. Both the functional redundancy of receptors and the experimental model used can lead to variable results. Therefore, it can be informative to explore alternative animal models to analyze ZIKV receptor candidates as an aid in discovering antivirals. This study used chicken embryos to examine the role of chicken Tyro3 (cTyro3), the equivalent of human Axl. Results show that endogenous cTyro3 mRNA expression overlaps with previously described hot spots of ZIKV infectivity in the brain and inner ear. We asked if ectopic expression or knockdown of cTyro3 influenced ZIKV infection in embryos. Tol2 vectors or replication-competent avian retroviruses were used in ovo to introduce full-length or truncated (presumed dominant-negative) cTyro3, respectively, into the neural tube on embryonic day two (E2). ZIKV was delivered to the brain 24 h later. cTyro3 manipulations did not alter ZIKV infection or cell death in the E5/E6 brain. Moreover, delivery of truncated cTyro3 variants to the E3 otocyst had no effect on inner ear formation on E6 or E10. Full article
(This article belongs to the Special Issue Zika Virus: An Emerging Flavivirus)
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3 pages, 196 KiB  
Editorial
Editorial: Infectious Disease Epidemiology and Transmission Dynamics
by Zhanwei Du, Wei Luo, Rachel Sippy and Lin Wang
Viruses 2023, 15(1), 246; https://doi.org/10.3390/v15010246 - 15 Jan 2023
Viewed by 1483
Abstract
Infectious diseases, such as COVID-19 [...] Full article
(This article belongs to the Special Issue Infectious Disease Epidemiology and Transmission Dynamics)
32 pages, 3930 KiB  
Article
Detection and Molecular Characterization of the SARS-CoV-2 Delta Variant and the Specific Immune Response in Companion Animals in Switzerland
by Evelyn Kuhlmeier, Tatjana Chan, Cecilia Valenzuela Agüí, Barbara Willi, Aline Wolfensberger, Christian Beisel, Ivan Topolsky, Niko Beerenwinkel, Tanja Stadler, Swiss SARS-CoV-2 Sequencing Consortium, Sarah Jones, Grace Tyson, Margaret J. Hosie, Katja Reitt, Julia Hüttl, Marina L. Meli and Regina Hofmann-Lehmann
Viruses 2023, 15(1), 245; https://doi.org/10.3390/v15010245 - 15 Jan 2023
Cited by 8 | Viewed by 5805
Abstract
In human beings, there are five reported variants of concern of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). However, in contrast to human beings, descriptions of infections of animals with specific variants are still rare. The aim of this study is to [...] Read more.
In human beings, there are five reported variants of concern of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). However, in contrast to human beings, descriptions of infections of animals with specific variants are still rare. The aim of this study is to systematically investigate SARS-CoV-2 infections in companion animals in close contact with SARS-CoV-2-positive owners (“COVID-19 households”) with a focus on the Delta variant. Samples, obtained from companion animals and their owners were analyzed using a real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) and next-generation sequencing (NGS). Animals were also tested for antibodies and neutralizing activity against SARS-CoV-2. Eleven cats and three dogs in nine COVID-19-positive households were RT-qPCR and/or serologically positive for the SARS-CoV-2 Delta variant. For seven animals, the genetic sequence could be determined. The animals were infected by one of the pangolin lineages B.1.617.2, AY.4, AY.43 and AY.129 and between zero and three single-nucleotide polymorphisms (SNPs) were detected between the viral genomes of animals and their owners, indicating within-household transmission between animal and owner and in multi-pet households also between the animals. NGS data identified SNPs that occur at a higher frequency in the viral sequences of companion animals than in viral sequences of humans, as well as SNPs, which were exclusively found in the animals investigated in the current study and not in their owners. In conclusion, our study is the first to describe the SARS-CoV-2 Delta variant transmission to animals in Switzerland and provides the first-ever description of Delta-variant pangolin lineages AY.129 and AY.4 in animals. Our results reinforce the need of a One Health approach in the monitoring of SARS-CoV-2 in animals. Full article
(This article belongs to the Special Issue Viral Infections in Companion Animals: Volume 2)
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10 pages, 570 KiB  
Communication
Antiviral Susceptibilities of Distinct Lineages of Influenza C and D Viruses
by Emi Takashita, Shin Murakami, Yoko Matsuzaki, Seiichiro Fujisaki, Hiroko Morita, Shiho Nagata, Misa Katayama, Katsumi Mizuta, Hidekazu Nishimura, Shinji Watanabe, Taisuke Horimoto and Hideki Hasegawa
Viruses 2023, 15(1), 244; https://doi.org/10.3390/v15010244 - 15 Jan 2023
Cited by 2 | Viewed by 1764
Abstract
The emergence and spread of antiviral-resistant influenza viruses are of great concern. To minimize the public health risk, it is important to monitor antiviral susceptibilities of influenza viruses. Analyses of the antiviral susceptibilities of influenza A and B viruses have been conducted globally; [...] Read more.
The emergence and spread of antiviral-resistant influenza viruses are of great concern. To minimize the public health risk, it is important to monitor antiviral susceptibilities of influenza viruses. Analyses of the antiviral susceptibilities of influenza A and B viruses have been conducted globally; however, those of influenza C and D viruses are limited. Here, we determined the susceptibilities of influenza C viruses representing all six lineages (C/Taylor, C/Yamagata, C/Sao Paulo, C/Aichi, C/Kanagawa, and C/Mississippi) and influenza D viruses representing four lineages (D/OK, D/660, D/Yama2016, and D/Yama2019) to RNA polymerase inhibitors (baloxavir and favipiravir) by using a focus reduction assay. All viruses tested were susceptible to both drugs. We then performed a genetic analysis to check for amino acid substitutions associated with baloxavir and favipiravir resistance and found that none of the viruses tested possessed these substitutions. Use of the focus reduction assay with the genotypic assay has proven valuable for monitoring the antiviral susceptibilities of influenza C and D viruses as well as influenza A and B viruses. Antiviral susceptibility monitoring of all influenza virus types should continue in order to assess the public health risks posed by these viruses. Full article
(This article belongs to the Special Issue Non-A Influenza 3.0)
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14 pages, 2728 KiB  
Article
Omicron-BA.1 Dispersion Rates in Mexico Varied According to the Regional Epidemic Patterns and the Diversity of Local Delta Subvariants
by Selene Zárate, Blanca Taboada, Mauricio Rosales-Rivera, Rodrigo García-López, José Esteban Muñoz-Medina, Alejandro Sanchez-Flores, Alfredo Herrera-Estrella, Bruno Gómez-Gil, Nelly Selem Mojica, Angel Gustavo Salas-Lais, Joel Armando Vazquez-Perez, David Alejandro Cabrera-Gaytán, Larissa Fernandes-Matano, Luis Antonio Uribe-Noguez, Juan Bautista Chale-Dzul, Brenda Irasema Maldonado Meza, Fidencio Mejía-Nepomuceno, Rogelio Pérez-Padilla, Rosa María Gutiérrez-Ríos, Antonio Loza, Benjamin Roche, Susana López and Carlos F. Ariasadd Show full author list remove Hide full author list
Viruses 2023, 15(1), 243; https://doi.org/10.3390/v15010243 - 15 Jan 2023
Cited by 5 | Viewed by 2291
Abstract
Purpose: The Omicron subvariant BA.1 of SARS-CoV-2 was first detected in November 2021 and quickly spread worldwide, displacing the Delta variant. In this work, a characterization of the spread of this variant in Mexico is presented. Methods: The time to fixation of BA.1, [...] Read more.
Purpose: The Omicron subvariant BA.1 of SARS-CoV-2 was first detected in November 2021 and quickly spread worldwide, displacing the Delta variant. In this work, a characterization of the spread of this variant in Mexico is presented. Methods: The time to fixation of BA.1, the diversity of Delta sublineages, the population density, and the level of virus circulation during the inter-wave interval were determined to analyze differences in BA.1 spread. Results: BA.1 began spreading during the first week of December 2021 and became dominant in the next three weeks, causing the fourth COVID-19 epidemiological surge in Mexico. Unlike previous variants, BA.1 did not exhibit a geographically distinct circulation pattern. However, a regional difference in the speed of the replacement of the Delta variant was observed. Conclusions: Viral diversity and the relative abundance of the virus in a particular area around the time of the introduction of a new lineage seem to have influenced the spread dynamics, in addition to population density. Nonetheless, if there is a significant difference in the fitness of the variants, or if the time allowed for the competition is sufficiently long, it seems the fitter virus will eventually become dominant, as observed in the eventual dominance of the BA.1.x variant in Mexico. Full article
(This article belongs to the Special Issue Molecular Epidemiology of SARS-CoV-2)
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19 pages, 10056 KiB  
Article
Urine Metabolome Dynamics Discriminate Influenza Vaccination Response
by Tori C. Rodrick, Yik Siu, Michael A. Carlock, Ted M. Ross and Drew R. Jones
Viruses 2023, 15(1), 242; https://doi.org/10.3390/v15010242 - 14 Jan 2023
Cited by 1 | Viewed by 2624
Abstract
Influenza represents a major and ongoing public health hazard. Current collaborative efforts are aimed toward creating a universal flu vaccine with the goals of both improving responses to vaccination and increasing the breadth of protection against multiple strains and clades from a single [...] Read more.
Influenza represents a major and ongoing public health hazard. Current collaborative efforts are aimed toward creating a universal flu vaccine with the goals of both improving responses to vaccination and increasing the breadth of protection against multiple strains and clades from a single vaccine. As an intermediate step toward these goals, the current work is focused on evaluating the systemic host response to vaccination in both normal and high-risk populations, such as the obese and geriatric populations, which have been linked to poor responses to vaccination. We therefore employed a metabolomics approach using a time-course (n = 5 time points) of the response to human vaccination against influenza from the time before vaccination (pre) to 90 days following vaccination. We analyzed the urinary profiles of a cohort of subjects (n = 179) designed to evenly sample across age, sex, BMI, and other demographic factors, stratifying their responses to vaccination as “High”, “Low”, or “None” based on the seroconversion measured by hemagglutination inhibition assay (HAI) from plasma samples at day 28 post-vaccination. Overall, we putatively identified 15,903 distinct, named, small-molecule structures (4473 at 10% FDR) among the 895 samples analyzed, with the aim of identifying metabolite correlates of the vaccine response, as well as prognostic and diagnostic markers from the periods before and after vaccination, respectively. Notably, we found that the metabolic profiles could unbiasedly separate the high-risk High-responders from the high-risk None-responders (obese/geriatric) within 3 days post-vaccination. The purine metabolites Guanine and Hypoxanthine were negatively associated with high seroconversion (p = 0.0032, p < 0.0001, respectively), while Acetyl-Leucine and 5-Aminovaleric acid were positively associated. Further changes in Cystine, Glutamic acid, Kynurenine and other metabolites implicated early oxidative stress (3 days) after vaccination as a hallmark of the High-responders. Ongoing efforts are aimed toward validating these putative markers using a ferret model of influenza infection, as well as an independent cohort of human seasonal vaccination and human challenge studies with live virus. Full article
(This article belongs to the Special Issue Advances in Universal Influenza Vaccines and Therapies)
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12 pages, 1772 KiB  
Perspective
ADP-Ribosylation and Antiviral Resistance in Plants
by Nadezhda Spechenkova, Natalya O. Kalinina, Sergey K. Zavriev, Andrew J. Love and Michael Taliansky
Viruses 2023, 15(1), 241; https://doi.org/10.3390/v15010241 - 14 Jan 2023
Cited by 2 | Viewed by 1855
Abstract
ADP-ribosylation (ADPRylation) is a versatile posttranslational modification in eukaryotic cells which is involved in the regulation of a wide range of key biological processes, including DNA repair, cell signalling, programmed cell death, growth and development and responses to biotic and abiotic stresses. Members [...] Read more.
ADP-ribosylation (ADPRylation) is a versatile posttranslational modification in eukaryotic cells which is involved in the regulation of a wide range of key biological processes, including DNA repair, cell signalling, programmed cell death, growth and development and responses to biotic and abiotic stresses. Members of the poly(ADP-ribosyl) polymerase (PARP) family play a central role in the process of ADPRylation. Protein targets can be modified by adding either a single ADP-ribose moiety (mono(ADP-ribosyl)ation; MARylation), which is catalysed by mono(ADP-ribosyl) transferases (MARTs or PARP “monoenzymes”), or targets may be decorated with chains of multiple ADP-ribose moieties (PARylation), via the activities of PARP “polyenzymes”. Studies have revealed crosstalk between PARylation (and to a lesser extent, MARylation) processes in plants and plant–virus interactions, suggesting that these tight links may represent a novel factor regulating plant antiviral immunity. From this perspective, we go through the literature linking PARylation-associated processes with other plant regulation pathways controlling virus resistance. Once unraveled, these links may serve as the basis of innovative strategies to improve crop resistance to viruses under challenging environmental conditions which could mitigate yield losses. Full article
(This article belongs to the Special Issue Plant Viruses: Pirates of Cellular Pathways)
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16 pages, 8056 KiB  
Article
Evolutionary Origin, Genetic Recombination, and Phylogeography of Porcine Kobuvirus
by Yongqiu Cui, Jingyi Li, Jinshuo Guo, Yang Pan, Xinxin Tong, Changzhe Liu, Dedong Wang, Weiyin Xu, Yongyan Shi, Ying Ji, Yonghui Qiu, Xiaoyu Yang, Lei Hou, Jianwei Zhou, Xufei Feng, Yong Wang and Jue Liu
Viruses 2023, 15(1), 240; https://doi.org/10.3390/v15010240 - 14 Jan 2023
Cited by 1 | Viewed by 1899
Abstract
The newly identified porcine Kobuvirus (PKV) has raised concerns owing to its association with diarrheal symptom in pigs worldwide. The process involving the emergence and global spread of PKV remains largely unknown. Here, the origin, genetic diversity, and geographic distribution of PKV were [...] Read more.
The newly identified porcine Kobuvirus (PKV) has raised concerns owing to its association with diarrheal symptom in pigs worldwide. The process involving the emergence and global spread of PKV remains largely unknown. Here, the origin, genetic diversity, and geographic distribution of PKV were determined based on the available PKV sequence information. PKV might be derived from the rabbit Kobuvirus and sheep were an important intermediate host. The most recent ancestor of PKV could be traced back to 1975. Two major clades are identified, PKVa and PKVb, and recombination events increase PKV genetic diversity. Cross-species transmission of PKV might be linked to interspecies conserved amino acids at 13–17 and 25–40 residue motifs of Kobuvirus VP1 proteins. Phylogeographic analysis showed that Spain was the most likely location of PKV origin, which then spread to pig-rearing countries in Asia, Africa, and Europe. Within China, the Hubei province was identified as a primary hub of PKV, transmitting to the east, southwest, and northeast regions of the country. Taken together, our findings have important implications for understanding the evolutionary origin, genetic recombination, and geographic distribution of PKV thereby facilitating the design of preventive and containment measures to combat PKV infection. Full article
(This article belongs to the Special Issue Advances in Veterinary Virology)
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13 pages, 969 KiB  
Article
Growth, Pathogenesis, and Serological Characteristics of the Japanese Encephalitis Virus Genotype IV Recent Strain 19CxBa-83-Cv
by Shigeru Tajima, Takahiro Maeki, Eri Nakayama, Astri Nur Faizah, Daisuke Kobayashi, Haruhiko Isawa, Yoshihide Maekawa, Sri Subekti Bendryman, Kris Cahyo Mulyatno, Etik Ainun Rohmah, Yasuko Mori, Kyoko Sawabe, Hideki Ebihara and Chang-Kweng Lim
Viruses 2023, 15(1), 239; https://doi.org/10.3390/v15010239 - 14 Jan 2023
Cited by 1 | Viewed by 2165
Abstract
Genotype IV Japanese encephalitis (JE) virus (GIV JEV) is the least common and most neglected genotype in JEV. We evaluated the growth and pathogenic potential of the GIV strain 19CxBa-83-Cv, which was isolated from a mosquito pool in Bali, Indonesia, in 2019, and [...] Read more.
Genotype IV Japanese encephalitis (JE) virus (GIV JEV) is the least common and most neglected genotype in JEV. We evaluated the growth and pathogenic potential of the GIV strain 19CxBa-83-Cv, which was isolated from a mosquito pool in Bali, Indonesia, in 2019, and serological analyses were also conducted. The growth ability of 19CxBa-83-Cv in Vero cells was intermediate between that of the genotype I (GI) strain Mie/41/2002 and the genotype V (GV) strain Muar, whereas 19CxBa-83-Cv and Mie/41/2002 grew faster than Muar in mouse neuroblastoma cells. The neuroinvasiveness of 19CxBa-83-Cv in mice was higher than that of Mie/41/2002 but lower than that of Muar; however, there were no significant differences in neurovirulence in mice among the three strains. The neutralizing titers of sera from 19CxBa-83-Cv- and Mie/41/2002-inoculated mice against 19CxBa-83-Cv and Mie/41/2002 were similar, whereas the titers against Muar were lower than those of the other two viruses. The neutralizing titers of JE vaccine-inoculated mouse pool serum against 19CxBa-83-Cv and Muar were significantly lower than those against Mie/41/2002. The neutralizing titers against the three viruses were similar in three out of the five serum samples from GI-infected JE patients, although the titers against Mie/41/2002 were higher than those against 19CxBa-83-Cv and Muar in the remaining two sera samples. In summary, we identified the basic characteristics of 19CxBa-83-Cv, but further studies are needed to better understand GIV JEV. Full article
(This article belongs to the Special Issue Japanese Encephalitis Virus)
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23 pages, 9526 KiB  
Article
Determining the Protective Efficacy of Toll-Like Receptor Ligands to Minimize H9N2 Avian Influenza Virus Transmission in Chickens
by Sugandha Raj, Mohammadali Alizadeh, Bahram Shoojadoost, Douglas Hodgins, Éva Nagy, Samira Mubareka, Khalil Karimi, Shahriar Behboudi and Shayan Sharif
Viruses 2023, 15(1), 238; https://doi.org/10.3390/v15010238 - 14 Jan 2023
Cited by 6 | Viewed by 2063
Abstract
Low-pathogenicity avian influenza viruses (AIV) of the H9N2 subtype can infect and cause disease in chickens. Little is known about the efficacy of immune-based strategies for reducing the transmission of these viruses. The present study investigated the efficacy of Toll-like receptor (TLR) ligands [...] Read more.
Low-pathogenicity avian influenza viruses (AIV) of the H9N2 subtype can infect and cause disease in chickens. Little is known about the efficacy of immune-based strategies for reducing the transmission of these viruses. The present study investigated the efficacy of Toll-like receptor (TLR) ligands (CpG ODN 2007 and poly(I:C)) to reduce H9N2 AIV transmission from TLR-treated seeder (trial 1) or inoculated chickens (trial 2) to naive chickens. The results from trial 1 revealed that a low dose of CpG ODN 2007 led to the highest reduction in oral shedding, and a high dose of poly(I:C) was effective at reducing oral and cloacal shedding. Regarding transmission, the recipient chickens exposed to CpG ODN 2007 low-dose-treated seeder chickens showed a maximum reduction in shedding with the lowest number of AIV+ chickens. The results from trial 2 revealed a maximum reduction in oral and cloacal shedding in the poly(I:C) high-dose-treated chickens (recipients), followed by the low-dose CpG ODN 2007 group. In these two groups, the expression of type I interferons (IFNs), protein kinase R (PKR), interferon-induced transmembrane protein 3 (IFITM3), viperin, and (interleukin) IL-1β, IL-8, and 1L-18 was upregulated in the spleen, cecal tonsils and lungs. Hence, TLR ligands can reduce AIV transmission in chickens. Full article
(This article belongs to the Special Issue Avian Respiratory Viruses, Volume III)
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14 pages, 1320 KiB  
Review
Heparanase-1: From Cancer Biology to a Future Antiviral Target
by Nadjet Lebsir, Fabien Zoulim and Boyan Grigorov
Viruses 2023, 15(1), 237; https://doi.org/10.3390/v15010237 - 14 Jan 2023
Cited by 3 | Viewed by 3142
Abstract
Heparan sulfate proteoglycans (HSPGs) are a major constituent of the extracellular matrix (ECM) and are found to be implicated in viral infections, where they play a role in both cell entry and release for many viruses. The enzyme heparanase-1 is the only known [...] Read more.
Heparan sulfate proteoglycans (HSPGs) are a major constituent of the extracellular matrix (ECM) and are found to be implicated in viral infections, where they play a role in both cell entry and release for many viruses. The enzyme heparanase-1 is the only known endo-beta-D-glucuronidase capable of degrading heparan sulphate (HS) chains of HSPGs and is thus important for regulating ECM homeostasis. Heparanase-1 expression is tightly regulated as the uncontrolled cleavage of HS may result in abnormal cell activation and significant tissue damage. The overexpression of heparanase-1 correlates with pathological scenarios and is observed in different human malignancies, such as lymphoma, breast, colon, lung, and hepatocellular carcinomas. Interestingly, heparanase-1 has also been documented to be involved in numerous viral infections, e.g., HSV-1, HPV, DENV. Moreover, very recent reports have demonstrated a role of heparanase-1 in HCV and SARS-CoV-2 infections. Due to the undenied pro-carcinogenic role of heparanase-1, multiple inhibitors have been developed, some reaching phase II and III in clinical studies. However, the use of heparanase inhibitors as antivirals has not yet been proposed. If it can be assumed that heparanase-1 is implicated in numerous viral life cycles, its inhibition by specific heparanase-acting compounds should result in a blockage of viral infection. This review addresses the perspectives of using heparanase inhibitors, not only for cancer treatment, but also as antivirals. Eventually, the development of a novel class antivirals targeting a cellular protein could help to alleviate the resistance problems seen with some current antiretroviral therapies. Full article
(This article belongs to the Section General Virology)
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20 pages, 1230 KiB  
Review
Viral Metagenomics as a Tool to Track Sources of Fecal Contamination: A One Health Approach
by Tasha M. Santiago-Rodriguez and Emily B. Hollister
Viruses 2023, 15(1), 236; https://doi.org/10.3390/v15010236 - 14 Jan 2023
Cited by 3 | Viewed by 3175
Abstract
The One Health framework recognizes that human, animal, and environmental health are linked and highly interdependent. Fecal contamination of water, soil, foodstuff, and air may impact many aspects of One Health, and culture, PCR-based, and sequencing methods are utilized in the detection of [...] Read more.
The One Health framework recognizes that human, animal, and environmental health are linked and highly interdependent. Fecal contamination of water, soil, foodstuff, and air may impact many aspects of One Health, and culture, PCR-based, and sequencing methods are utilized in the detection of fecal contamination to determine source, load, and risk to inform targeted mitigation strategies. Viruses, particularly, have been considered as fecal contamination indicators given the narrow host range many exhibit and their association with other biological contaminants. Culture- and molecular-based methods are considered the gold-standards for virus detection and for determining specific sources of fecal contamination via viral indicators. However, viral metagenomics is also being considered as a tool for tracking sources of fecal contamination. In the present review, studies tracking potential sources of fecal contamination in freshwaters, marine waters, foodstuff, soil, and air using viral metagenomics are discussed to highlight the potential of viral metagenomics for optimizing fecal source tracking. Limitations of the use of viral metagenomics to track fecal contamination sources, including sample processing, nucleic acid recovery, sequencing depth, and bioinformatics are also discussed. Finally, the present review discusses the potential of viral metagenomics as part of the toolbox of methods in a One Health approach. Full article
(This article belongs to the Section General Virology)
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23 pages, 3742 KiB  
Article
Culex Y Virus: A Native Virus of Culex Species Characterized In Vivo
by Mareike Heinig-Hartberger, Fanny Hellhammer, David D. J. A. Zöller, Susann Dornbusch, Stella Bergmann, Katerina Vocadlova, Sandra Junglen, Michael Stern, Kwang-Zin Lee and Stefanie C. Becker
Viruses 2023, 15(1), 235; https://doi.org/10.3390/v15010235 - 14 Jan 2023
Cited by 6 | Viewed by 2097
Abstract
Mosquitoes are vectors of various pathogens that cause diseases in humans and animals. To prevent the outbreak of mosquito-borne diseases, it is essential to control vector populations, as treatment or vaccination for mosquito-borne diseases are often unavailable. Insect-specific viruses (ISVs) have previously been [...] Read more.
Mosquitoes are vectors of various pathogens that cause diseases in humans and animals. To prevent the outbreak of mosquito-borne diseases, it is essential to control vector populations, as treatment or vaccination for mosquito-borne diseases are often unavailable. Insect-specific viruses (ISVs) have previously been described as being potentially helpful against arboviral disease outbreaks. In this study, we present the first in vivo characterization of the ISV Culex Y virus (CYV). CYV was first isolated from free-living Culex pipiens mosquitoes in 2010; then, it was found in several mosquito cell lines in a further study in 2018. For mammalian cells, we were able to confirm that CYV does not replicate as it was previously described. Additionally, we found that CYV does not replicate in honey bees or locusts. However, we detected replication in the Culex pipiens biotype molestus, Aedes albopictus, and Drosophila melanogaster, thus indicating dipteran specificity. We detected significantly higher mortality in Culex pipiens biotype molestus males and Drosophila melanogaster, but not in Aedes albopictus and female Culex pipiens biotype molestus. CYV could not be transmitted transovarially to offspring, but we detected venereal transmission as well as CYV in mosquitos’ saliva, indicating that an oral route of infection would also be possible. CYV’s dipteran specificity, transmission routes, and killing effect with respect to Culex males may be used as powerful tools with which to destabilize arbovirus vector populations in the future. Full article
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10 pages, 529 KiB  
Communication
Association between Anti-DENV IgM Serum Prevalence and CD11b Expression by Classical Monocytes in Obesity
by Karine Beatriz Costa, Bruna Caroline Chaves Garcia, Marina Luiza Baêta Costa, Yara Gomes Pena, Eduardo Augusto Barbosa Figueiredo, Marcelo Henrique Fernandes Ottoni, Juliane Duarte Santos, Vinícius de Oliveira Ottone, Danilo Bretas de Oliveira and Etel Rocha-Vieira
Viruses 2023, 15(1), 234; https://doi.org/10.3390/v15010234 - 14 Jan 2023
Viewed by 1472
Abstract
Dengue and obesity are currently highly prevalent conditions worldwide and the association between these two conditions may result in greater risk for DENV infection and disease severity. In this study the association between obesity and recent, inapparent dengue was investigated. Serum DENV IgM [...] Read more.
Dengue and obesity are currently highly prevalent conditions worldwide and the association between these two conditions may result in greater risk for DENV infection and disease severity. In this study the association between obesity and recent, inapparent dengue was investigated. Serum DENV IgM and NS1 were evaluated in 49 adult volunteers (15 lean and 34 individuals with obesity, according to body mass index), between September 2017 and June 2018. Adiposity, endocrine, metabolic, and immune data of the participants were also obtained. None of the study participants tested positive for the DENV NS1 antigen. DENV IgM was detected in 33.3% of the lean individuals, and in 44.1% of those with obesity; the presence of DENV IgM was not associated with body mass index (OR = 1.32, 95% CI = 0.59–2.98, p = 0.48). However, body fat index was higher in obese individuals who had recent inapparent dengue (14.7 ± 3.1 versus 12.7 ± 2.1 kg/m2, p = 0.04), as was the expression of CD11b by classical (CD14++CD16) monocytes (1103.0 ± 311.3 versus 720.3 ± 281.1 mean fluoresce intensity). Our findings suggest an association between adiposity and recent inapparent dengue and the involvement of classical monocytes in this association. Full article
(This article belongs to the Section Human Virology and Viral Diseases)
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34 pages, 555 KiB  
Review
African Swine Fever Virus Infection and Cytokine Response In Vivo: An Update
by Giulia Franzoni, Miriam Pedrera and Pedro J. Sánchez-Cordón
Viruses 2023, 15(1), 233; https://doi.org/10.3390/v15010233 - 14 Jan 2023
Cited by 9 | Viewed by 3822
Abstract
African swine fever (ASF) is a hemorrhagic viral disease of domestic pigs and wild suids (all Sus scrofa) caused by the ASF virus (ASFV). The disease is spreading worldwide without control, threatening pig production due to the absence of licensed vaccine or [...] Read more.
African swine fever (ASF) is a hemorrhagic viral disease of domestic pigs and wild suids (all Sus scrofa) caused by the ASF virus (ASFV). The disease is spreading worldwide without control, threatening pig production due to the absence of licensed vaccine or commercially available treatments. A thorough understanding of the immunopathogenic mechanisms behind ASFV infection is required to better fight the disease. Cytokines are small, non-structural proteins, which play a crucial role in many aspects of the immune responses to viruses, including ASFV. Infection with virulent ASFV isolates often results in exacerbated immune responses, with increased levels of serum pro-inflammatory interleukins (IL-1α, IL-1β, IL-6), TNF and chemokines (CCL2, CCL5, CXCL10). Increased levels of IL-1, IL-6 and TNF are often detected in several tissues during acute ASFV infections and associated with lymphoid depletion, hemorrhages and oedemas. IL-1Ra is frequently released during ASFV infection to block further IL-1 activity, with its implication in ASFV immunopathology having been suggested. Increased levels of IFN-α and of the anti-inflammatory IL-10 seem to be negatively correlated with animal survival, whereas some correlation between virus-specific IFN-γ-producing cells and protection has been suggested in different studies where different vaccine candidates were tested, although future works should elucidate whether IFN-γ release by specific cell types is related to protection or disease development. Full article
(This article belongs to the Special Issue African Swine Fever Virus: Infection and Immunity)
16 pages, 874 KiB  
Article
COVID-19 Clusters in Belgian Nursing Homes: Impact of Facility Characteristics and Vaccination on Cluster Occurrence, Duration and Severity
by Sara Dequeker, Milena Callies, Lucy Catteau, Laura Int Panis, Esma Islamaj, Sofieke Klamer, Katrien Latour, Marijke Pauwels, Catharina Vernemmen, Romain Mahieu, Hanna Masson, Muhammet Savsin, Etienne De Clercq, Mireille Thomas, Boudewijn Catry and Eline Vandael
Viruses 2023, 15(1), 232; https://doi.org/10.3390/v15010232 - 13 Jan 2023
Cited by 2 | Viewed by 1929
Abstract
COVID-19 severely affected nursing home residents from March 2020 onwards in Belgium. This study aimed to model the impact of vaccination and facility characteristics on cluster occurrence, duration and severity in this setting. Possible clusters were identified between June 2020 and January 2022, [...] Read more.
COVID-19 severely affected nursing home residents from March 2020 onwards in Belgium. This study aimed to model the impact of vaccination and facility characteristics on cluster occurrence, duration and severity in this setting. Possible clusters were identified between June 2020 and January 2022, based on the Belgian COVID-19 surveillance in nursing homes. Median attack rates (AR) among residents and staff, case hospitalization rates (CHR) and case fatality rates (CFR) were calculated. A negative binomial model was used to identify the association between nursing home characteristics and the number of cases, hospital admissions and deaths and the duration of the cluster. A total of 2239 clusters were detected in more than 80% of nursing homes. Most of these (62%) occurred before the start of COVID-19 vaccination (end of December 2020). After vaccination, the number of clusters, the AR among residents and staff, the CHR and the CFR dropped. Previous cluster(s) and vaccination decreased the number of cases, hospital admissions and deaths among residents. Previous cluster experience and having started vaccination were protective factors. We recommend continued implementation of targeted interventions such as vaccination, large-scale screening and immediate implementation of additional infection prevention and control measures. Full article
(This article belongs to the Section SARS-CoV-2 and COVID-19)
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20 pages, 4076 KiB  
Article
Biological Properties of 12 Newly Isolated Acinetobacter baumannii-Specific Bacteriophages
by Natalia Bagińska, Marek Adam Harhala, Martyna Cieślik, Filip Orwat, Beata Weber-Dąbrowska, Krystyna Dąbrowska, Andrzej Górski and Ewa Jończyk-Matysiak
Viruses 2023, 15(1), 231; https://doi.org/10.3390/v15010231 - 13 Jan 2023
Cited by 7 | Viewed by 2586
Abstract
Infections with the opportunistic Gram-negative bacterium Acinetobacter baumannii pose a serious threat today, which is aggravated by the growing problem of multi-drug resistance among bacteria, caused by the overuse of antibiotics. Treatment of infections caused by antibiotic-resistant A. baumannii strains with the use [...] Read more.
Infections with the opportunistic Gram-negative bacterium Acinetobacter baumannii pose a serious threat today, which is aggravated by the growing problem of multi-drug resistance among bacteria, caused by the overuse of antibiotics. Treatment of infections caused by antibiotic-resistant A. baumannii strains with the use of phage therapy is not only a promising alternative, but sometimes the only option. Therefore, phages specific for clinical multi-drug resistant A. baumannii were searched for in environmental, municipal, and hospital wastewater samples collected from different locations in Poland. The conducted research allowed us to determine the biological properties and morphology of the tested phages. As a result of our research, 12 phages specific for A. baumannii, 11 of which turned out to be temperate and only one lytic, were isolated. Their lytic spectra ranged from 11 to 75%. The plaques formed by most phages were small and transparent, while one of them formed relatively large plaques with a clearly marked ‘halo’ effect. Based on Transmission Electron Microscopy (TEM), most of our phages have been classified as siphoviruses (only one phage was classified as a podovirus). All phages have icosahedral capsid symmetry, and 11 of them have a long tail. Optimal multiplicity of infections (MOIs) and the adsorption rate were also determined. MOI values varied depending on the phage—from 0.001 to 10. Based on similarities to known bacteriophages, our A. baumannii-specific phages have been proposed to belong to the Beijerinckvirinae and Junivirinae subfamilies. This study provides an additional tool in the fight against this important pathogen and may boost the interest in phage therapy as an alternative and supplement to the current antibiotics. Full article
(This article belongs to the Section Bacterial Viruses)
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14 pages, 2320 KiB  
Article
Assessment of Immunogenic and Antigenic Properties of Recombinant Nucleocapsid Proteins of Five SARS-CoV-2 Variants in a Mouse Model
by Alexandra Rak, Nikolay Gorbunov, Valeria Kostevich, Alexey Sokolov, Polina Prokopenko, Larisa Rudenko and Irina Isakova-Sivak
Viruses 2023, 15(1), 230; https://doi.org/10.3390/v15010230 - 13 Jan 2023
Cited by 3 | Viewed by 1680
Abstract
COVID-19 cases caused by new variants of highly mutable SARS-CoV-2 continue to be identified worldwide. Effective control of the spread of new variants can be achieved through targeting of conserved viral epitopes. In this regard, the SARS-CoV-2 nucleocapsid (N) protein, which is much [...] Read more.
COVID-19 cases caused by new variants of highly mutable SARS-CoV-2 continue to be identified worldwide. Effective control of the spread of new variants can be achieved through targeting of conserved viral epitopes. In this regard, the SARS-CoV-2 nucleocapsid (N) protein, which is much more conserved than the evolutionarily influenced spike protein (S), is a suitable antigen. The recombinant N protein can be considered not only as a screening antigen but also as a basis for the development of next-generation COVID-19 vaccines, but little is known about induction of antibodies against the N protein via different SARS-CoV-2 variants. In addition, it is important to understand how antibodies produced against the antigen of one variant can react with the N proteins of other variants. Here, we used recombinant N proteins from five SARS-CoV-2 strains to investigate their immunogenicity and antigenicity in a mouse model and to obtain and characterize a panel of hybridoma-derived monoclonal anti-N antibodies. We also analyzed the variable epitopes of the N protein that are potentially involved in differential recognition of antiviral antibodies. These results will further deepen our knowledge of the cross-reactivity of the humoral immune response in COVID-19. Full article
(This article belongs to the Special Issue RNA Viruses and Antibody Response)
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