Viruses

12 pages, 1101 KiB

Open AccessArticle

Host Response Markers of Inflammation and Endothelial Activation Associated with COVID-19 Severity and Mortality: A GeoSentinel Prospective Observational Cohort

by Andrea M. Weckman, Sarah Anne J. Guagliardo, Valerie M. Crowley, Lucia Moro, Chiara Piubelli, Tamara Ursini, Sabrina H. van Ierssel, Federico G. Gobbi, Hannah Emetulu, Aisha Rizwan, Kristina M. Angelo, Carmelo Licitra, Bradley A. Connor, Sapha Barkati, Michelle Ngai, Kathleen Zhong, Ralph Huits, Davidson H. Hamer, Michael Libman and Kevin C. Kain

Viruses 2024, 16(10), 1615; https://doi.org/10.3390/v16101615 (registering DOI) - 15 Oct 2024

Abstract

Background: The effect of the COVID-19 pandemic on healthcare systems emphasized the need for rapid and effective triage tools to identify patients at risk of severe or fatal infection. Measuring host response markers of inflammation and endothelial activation at clinical presentation may help [...] Read more.

Background: The effect of the COVID-19 pandemic on healthcare systems emphasized the need for rapid and effective triage tools to identify patients at risk of severe or fatal infection. Measuring host response markers of inflammation and endothelial activation at clinical presentation may help to inform appropriate triage and care practices in patients with SARS-CoV-2 infection. Methods: We enrolled patients with COVID-19 across five GeoSentinel clinical sites (in Italy, Belgium, Canada, and the United States) from September 2020 to December 2021, and analyzed the association of plasma markers, including soluble urokinase-type plasminogen activator receptor (suPAR), soluble tumor necrosis factor receptor-1 (sTREM-1), interleukin-6 (IL-6), interleukin-8 (IL-8), complement component C5a (C5a), von Willebrand factor (VWF-a2), and interleukin-1 receptor antagonist (IL-1Ra), with 28-day (D28) mortality and 7-day (D7) severity (discharged, hospitalized on ward, or died/admitted to the ICU). Results: Of 193 patients, 8.9% (16 of 180) died by D28. Higher concentrations of suPAR were associated with increased odds of mortality at D28 and severity at D7 in univariable and multivariable regression models. The biomarkers sTREM-1 and IL-1Ra showed bivariate associations with mortality at D28 and severity at D7. IL-6, VWF, C5a, and IL-8 were not as indicative of progression to severe disease or death. Conclusions: Our findings confirm previous studies’ assertions that point-of-care tests for suPAR and sTREM-1 could facilitate the triage of patients with SARS-CoV-2 infection, which may help guide hospital resource allocation. Full article

(This article belongs to the Section Coronaviruses)

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19 pages, 2897 KiB

Open AccessArticle

Viral Diversity in Mixed Tree Fruit Production Systems Determined through Bee-Mediated Pollen Collection

by Raj Vansia, Malek Smadi, James Phelan, Aiming Wang, Guillaume J. Bilodeau, Stephen F. Pernal, M. Marta Guarna, Michael Rott and Jonathan S. Griffiths

Viruses 2024, 16(10), 1614; https://doi.org/10.3390/v16101614 (registering DOI) - 15 Oct 2024

Abstract

Commercially cultivated Prunus species are commonly grown in adjacent or mixed orchards and can be infected with unique or commonly shared viruses. Apple (Malus domestica), another member of the Rosacea and distantly related to Prunus, can share the same growing [...] Read more.

Commercially cultivated Prunus species are commonly grown in adjacent or mixed orchards and can be infected with unique or commonly shared viruses. Apple (Malus domestica), another member of the Rosacea and distantly related to Prunus, can share the same growing regions and common pathogens. Pollen can be a major route for virus transmission, and analysis of the pollen virome in tree fruit orchards can provide insights into these virus pathogen complexes from mixed production sites. Commercial honey bee (Apis mellifera) pollination is essential for improved fruit sets and yields in tree fruit production systems. To better understand the pollen-associated virome in tree fruits, metagenomics-based detection of plant viruses was employed on bee and pollen samples collected at four time points during the peak bloom period of apricot, cherry, peach, and apple trees at one orchard site. Twenty-one unique viruses were detected in samples collected during tree fruit blooms, including prune dwarf virus (PDV) and prunus necrotic ringspot virus (PNRSV) (Genus Ilarvirus, family Bromoviridae), Secoviridae family members tomato necrotic ringspot virus (genus Nepovirus), tobacco necrotic ringspot virus (genus Nepovirus), prunus virus F (genus Fabavirus), and Betaflexiviridae family member cherry virus A (CVA; genus Capillovirus). Viruses were also identified in composite leaf and flower samples to compare the pollen virome with the virome associated with vegetative tissues. At all four time points, a greater diversity of viruses was detected in the bee and pollen samples. Finally, the nucleotide sequence diversity of the coat protein regions of CVA, PDV, and PNRSV was profiled from this site, demonstrating a wide range of sequence diversity in pollen samples from this site. These results demonstrate the benefits of area-wide monitoring through bee pollination activities and provide new insights into the diversity of viruses in tree fruit pollination ecosystems. Full article

(This article belongs to the Special Issue Plant Virus Spillovers)

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14 pages, 518 KiB

Open AccessArticle

Prevalence of Antibodies against Adeno-Associated Viruses (AAVs) in Göttingen Minipigs and Its Implications for Gene Therapy and Xenotransplantation

by Kirsten Rosenmay Jacobsen, Javier Mota, Michelle Salerno, Alexis Willis, Dennis Pitts and Joachim Denner

Viruses 2024, 16(10), 1613; https://doi.org/10.3390/v16101613 (registering DOI) - 15 Oct 2024

Abstract

Adeno-associated viruses (AAV) are widely used as delivery vectors in clinical trials for in vivo gene therapy due to their unique features. Göttingen minipigs are a well-established animal model for several diseases and can be used for the efficacy and safety testing of [...] Read more.

Adeno-associated viruses (AAV) are widely used as delivery vectors in clinical trials for in vivo gene therapy due to their unique features. Göttingen minipigs are a well-established animal model for several diseases and can be used for the efficacy and safety testing of AAV-based gene therapy. Pre-existing antibodies against AAV may influence the results of testing and, therefore, the animals should be tested for the presence of antibodies against relevant AAV serotypes. The detection of AAVs in pigs may be also important for the virus safety of xenotransplantation. In this study, we screened Göttingen minipigs from Ellegaard Göttingen Minipigs A/S, Denmark, and Marshall BioResources, USA, for antibodies against AAV1, AAV2, AAV6, AAV9 serotypes. Of the 20 animals tested, 18 had no neutralizing antibodies for all AAVs tested, none had antibodies against AAV9, only one had antibodies against AAV6, and the titers of antibodies against AAV1 and AAV2 were less than 1:100, with two exceptions. For total binding IgG, more individuals showed positivity for all the tested serotypes but, in general, the levels were low or zero. Three animals had no antibodies at all against the AAVs tested. Therefore, Göttingen minipigs could be considered an attractive animal model for gene therapy studies. Since some animals were negative for all AAVs tested, these may be selected and used as donor animals for xenotransplantation. Full article

(This article belongs to the Special Issue Porcine Viruses 2024)

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26 pages, 2144 KiB

Open AccessReview

Monocyte and Macrophage Functions in Oncogenic Viral Infections

by Juliana Echevarria-Lima and Ramona Moles

Viruses 2024, 16(10), 1612; https://doi.org/10.3390/v16101612 (registering DOI) - 15 Oct 2024

Abstract

Monocytes and macrophages are part of innate immunity and constitute the first line of defense against pathogens. Bone marrow-derived monocytes circulate in the bloodstream for one to three days and then typically migrate into tissues, where they differentiate into macrophages. Circulatory monocytes represent [...] Read more.

Monocytes and macrophages are part of innate immunity and constitute the first line of defense against pathogens. Bone marrow-derived monocytes circulate in the bloodstream for one to three days and then typically migrate into tissues, where they differentiate into macrophages. Circulatory monocytes represent 5% of the nucleated cells in normal adult blood. Following differentiation, macrophages are distributed into various tissues and organs to take residence and maintain body homeostasis. Emerging evidence has highlighted the critical role of monocytes/macrophages in oncogenic viral infections, mainly their crucial functions in viral persistence and disease progression. These findings open opportunities to target innate immunity in the context of oncogenic viruses and to explore their potential as immunotherapies. Full article

(This article belongs to the Special Issue Chronic Infection by Oncogenic Viruses)

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15 pages, 3799 KiB

Open AccessArticle

The Replicase Protein of Potato Virus X Is Able to Recognize and Trans-Replicate Its RNA Component

by Pinky Dutta, Andres Lõhmus, Tero Ahola and Kristiina Mäkinen

Viruses 2024, 16(10), 1611; https://doi.org/10.3390/v16101611 (registering DOI) - 15 Oct 2024

Abstract

The trans-replication system explores the concept of separating the viral RNA involved in the translation of the replicase protein from the replication of the viral genome and has been successfully used to study the replication mechanisms of alphaviruses. We tested the feasibility [...] Read more.

The trans-replication system explores the concept of separating the viral RNA involved in the translation of the replicase protein from the replication of the viral genome and has been successfully used to study the replication mechanisms of alphaviruses. We tested the feasibility of this system with potato virus X (PVX), an alpha-like virus, in planta. A viral RNA template was designed which does not produce the replicase and prevents virion formation but remains recognizable by the replicase. The replicase construct encodes for the replicase protein, while lacking other virus-specific recognition sequences. Both the constructs were delivered into Nicotiana benthamiana leaves via Agrobacterium-mediated infiltration. Templates of various lengths were tested, with the longer templates not replicating at 4 and 6 days post inoculation, when the replicase protein was provided in trans. Co-expression of helper component proteinase with the short template led to its trans-replication. The cells where replication had been initiated were observed to be scattered across the leaf lamina. This study established that PVX is capable of trans-replicating and can likely be further optimized, and that the experimental freedom offered by the system can be utilized to delve deeper into understanding the replication mechanism of the virus. Full article

(This article belongs to the Special Issue Application of Genetically Engineered Plant Viruses)

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Graphical abstract

26 pages, 11150 KiB

Open AccessArticle

Expanding Insights: Harnessing Expansion Microscopy for Super-Resolution Analysis of HIV-1–Cell Interactions

by Annett Petrich, Gyu Min Hwang, Laetitia La Rocca, Mariam Hassan, Maria Anders-Össwein, Vera Sonntag-Buck, Anke-Mareil Heuser, Vibor Laketa, Barbara Müller, Hans-Georg Kräusslich and Severina Klaus

Viruses 2024, 16(10), 1610; https://doi.org/10.3390/v16101610 (registering DOI) - 15 Oct 2024

Abstract

Expansion microscopy has recently emerged as an alternative technique for achieving high-resolution imaging of biological structures. Improvements in resolution are achieved by physically expanding samples through embedding in a swellable hydrogel before microscopy. However, expansion microscopy has been rarely used in the field [...] Read more.

Expansion microscopy has recently emerged as an alternative technique for achieving high-resolution imaging of biological structures. Improvements in resolution are achieved by physically expanding samples through embedding in a swellable hydrogel before microscopy. However, expansion microscopy has been rarely used in the field of virology. Here, we evaluate and characterize the ultrastructure expansion microscopy (U-ExM) protocol, which facilitates approximately four-fold sample expansion, enabling the visualization of different post-entry stages of the HIV-1 life cycle, focusing on nuclear events. Our findings demonstrate that U-ExM provides robust sample expansion and preservation across different cell types, including cell-culture-adapted and primary CD4+ T-cells as well as monocyte-derived macrophages, which are known HIV-1 reservoirs. Notably, cellular targets such as nuclear bodies and the chromatin landscape remain well preserved after expansion, allowing for detailed investigation of HIV-1–cell interactions at high resolution. Our data indicate that morphologically distinct HIV-1 capsid assemblies can be differentiated within the nuclei of infected cells and that U-ExM enables detection of targets that are masked in commonly used immunofluorescence protocols. In conclusion, we advocate for U-ExM as a valuable new tool for studying virus–host interactions with enhanced spatial resolution. Full article

(This article belongs to the Special Issue Microscopy Methods for Virus Research)

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21 pages, 7364 KiB

Open AccessArticle

Double-Negative T-Cells during Acute Human Immunodeficiency Virus and Simian Immunodeficiency Virus Infections and Following Early Antiretroviral Therapy Initiation

by Alexis Yero, Tao Shi, Julien A. Clain, Ouafa Zghidi-Abouzid, Gina Racine, Cecilia T. Costiniuk, Jean-Pierre Routy, Jérôme Estaquier and Mohammad-Ali Jenabian

Viruses 2024, 16(10), 1609; https://doi.org/10.3390/v16101609 - 14 Oct 2024

Abstract

HIV infection significantly affects the frequencies and functions of immunoregulatory CD3⁺CD4⁻CD8⁻ double-negative (DN) T-cells, while the effect of early antiretroviral therapy (ART) initiation on these cells remains understudied. DN T-cell subsets were analyzed prospectively in 10 HIV+ individuals [...] Read more.

HIV infection significantly affects the frequencies and functions of immunoregulatory CD3⁺CD4⁻CD8⁻ double-negative (DN) T-cells, while the effect of early antiretroviral therapy (ART) initiation on these cells remains understudied. DN T-cell subsets were analyzed prospectively in 10 HIV+ individuals during acute infection and following early ART initiation compared to 20 HIV-uninfected controls. In this study, 21 Rhesus macaques (RMs) were SIV-infected, of which 13 were assessed during acute infection and 8 following ART initiation four days post-infection. DN T-cells and FoxP3⁺ DN Treg frequencies increased during acute HIV infection, which was not restored by ART. The expression of activation (HLA-DR/CD38), immune checkpoints (PD-1/CTLA-4), and senescence (CD28⁻CD57⁺) markers by DN T-cells and DN Tregs increased during acute infection and was not normalized by ART. In SIV-infected RMs, DN T-cells remained unchanged despite infection or ART, whereas DN Treg frequencies increased during acute SIV infection and were not restored by ART. Finally, frequencies of CD39⁺ DN Tregs increased during acute HIV and SIV infections and remained elevated despite ART. Altogether, acute HIV/SIV infections significantly changed DN T-cell and DN Treg frequencies and altered their immune phenotype, while these changes were not fully normalized by early ART, suggesting persistent HIV/SIV-induced immune dysregulation despite early ART initiation. Full article

(This article belongs to the Special Issue Acute HIV Infections)

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15 pages, 2518 KiB

Open AccessArticle

Molecular Characterization and Genomic Surveillance of SARS-CoV-2 Lineages in Central India

by Purna Dwivedi, Mukul Sharma, Afzal Ansari, Arup Ghosh, Subasa C. Bishwal, Suman Kumar Ray, Manish Katiyar, Subbiah Kombiah, Ashok Kumar, Lalit Sahare, Mahendra Ukey, Pradip V. Barde, Aparup Das and Pushpendra Singh

Viruses 2024, 16(10), 1608; https://doi.org/10.3390/v16101608 - 14 Oct 2024

Abstract

Since the first reported case of COVID-19 in December 2019, several SARS-CoV-2 variants have evolved, and some of them have shown higher transmissibility, becoming the prevalent strains. Genomic epidemiological investigations into strains from different time points, including the early stages of the pandemic, [...] Read more.

Since the first reported case of COVID-19 in December 2019, several SARS-CoV-2 variants have evolved, and some of them have shown higher transmissibility, becoming the prevalent strains. Genomic epidemiological investigations into strains from different time points, including the early stages of the pandemic, are very crucial for understanding the evolution and transmission patterns. Using whole-genome sequences, our study describes the early landscape of SARS-CoV-2 variants in central India retrospectively (including the first known occurrence of SARS-CoV-2 in Madhya Pradesh). We performed amplicon-based whole-genome sequencing of randomly selected SARS-CoV-2 isolates (n = 38) collected between 2020 and 2022 at state level VRDL, ICMR-NIRTH, Jabalpur, from 11899 RT-qPCR-positive samples. We observed the presence of five lineages, namely B.1, B.1.1, B.1.36.8, B.1.195, and B.6, in 19 genomes from the first wave cases and variants of concern (VOCs) lineages, i.e., B.1.617.2 (Delta) and BA.2.10 (Omicron) in the second wave cases. There was a shift in mutational pattern in the spike protein coding region of SRAS-CoV-2 strains from the second wave in contrast to the first wave. In the first wave of infections, we observed variations in the ORF1Ab region, and with the emergence of Delta lineages, the D614G mutation associated with an increase in infectivity became a prominent change. We have identified five immune escape variants in the S gene, P681R, P681H, L452R, Q57H, and N501Y, in the isolates collected during the second wave. Furthermore, these genomes were compared with 2160 complete genome sequences reported from central India that encompass 109 different SARS-CoV-2 lineages. Among them, VOC lineages Delta (28.93%) and Omicron (56.11%) were circulating predominantly in this region. This study provides useful insights into the genetic diversity of SARS-CoV-2 strains over the initial course of the COVID-19 pandemic in central India. Full article

(This article belongs to the Special Issue Molecular Epidemiology of SARS-CoV-2, 3rd Edition)

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15 pages, 4016 KiB

Open AccessArticle

Efficacy of Integrase Strand Transfer Inhibitors and the Capsid Inhibitor Lenacapavir against HIV-2, and Exploring the Effect of Raltegravir on the Activity of SARS-CoV-2

by Irene Wanjiru Kiarie, Gyula Hoffka, Manon Laporte, Pieter Leyssen, Johan Neyts, József Tőzsér and Mohamed Mahdi

Viruses 2024, 16(10), 1607; https://doi.org/10.3390/v16101607 - 13 Oct 2024

Abstract

Retroviruses perpetuate their survival by incorporating a copy of their genome into the host cell, a critical step catalyzed by the virally encoded integrase. The viral capsid plays an important role during the viral life cycle, including nuclear importation in the case of [...] Read more.

Retroviruses perpetuate their survival by incorporating a copy of their genome into the host cell, a critical step catalyzed by the virally encoded integrase. The viral capsid plays an important role during the viral life cycle, including nuclear importation in the case of lentiviruses and integration targeting events; hence, targeting the integrase and the viral capsid is a favorable therapeutic strategy. While integrase strand transfer inhibitors (INSTIs) are recommended as first-line regimens given their high efficacy and tolerability, lenacapavir is the first capsid inhibitor and the newest addition to the HIV treatment arsenal. These inhibitors are however designed for treatment of HIV-1 infection, and their efficacy against HIV-2 remains widely understudied and inconclusive, supported only by a few limited phenotypic susceptibility studies. We therefore carried out inhibition profiling of a panel of second-generation INSTIs and lenacapavir against HIV-2 in cell culture, utilizing pseudovirion inhibition profiling assays. Our results show that the tested INSTIs and lenacapavir exerted excellent efficacy against ROD-based HIV-2 integrase. We further evaluated the efficacy of raltegravir and other INSTIs against different variants of SARS-CoV-2; however, contrary to previous in silico findings, the inhibitors did not demonstrate significant antiviral activity. Full article

(This article belongs to the Special Issue Integrase Inhibitors 2023)

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16 pages, 2624 KiB

Open AccessArticle

Epidemiology and Ecology of Usutu Virus Infection and Its Global Risk Distribution

by Jiahao Chen, Yuanyuan Zhang, Xiaoai Zhang, Meiqi Zhang, Xiaohong Yin, Lei Zhang, Cong Peng, Bokang Fu, Liqun Fang and Wei Liu

Viruses 2024, 16(10), 1606; https://doi.org/10.3390/v16101606 - 12 Oct 2024

Abstract

Usutu virus (USUV) is an emerging mosquito-transmitted flavivirus with increasing incidence of human infection and geographic expansion, thus posing a potential threat to public health. In this study, we established a comprehensive spatiotemporal database encompassing USUV infections in vectors, animals, and humans worldwide [...] Read more.

Usutu virus (USUV) is an emerging mosquito-transmitted flavivirus with increasing incidence of human infection and geographic expansion, thus posing a potential threat to public health. In this study, we established a comprehensive spatiotemporal database encompassing USUV infections in vectors, animals, and humans worldwide by an extensive literature search. Based on this database, we characterized the geographic distribution and epidemiological features of USUV infections. By employing boosted regression tree (BRT) models, we projected the distributions of three main vectors (Culex pipiens, Aedes albopictus, and Culiseta longiareolata) and three main hosts (Turdus merula, Passer domesticus, and Ardea cinerea) to obtain the mosquito index and bird index. These indices were further incorporated as predictors into the USUV infection models. Through an ensemble learning model, we achieved a decent model performance, with an area under the curve (AUC) of 0.992. The mosquito index contributed significantly, with relative contributions estimated at 25.51%. Our estimations revealed a potential exposure area for USUV spanning 1.80 million km² globally with approximately 1.04 billion people at risk. This can guide future surveillance efforts for USUV infections, especially for countries located within high-risk areas and those that have not yet conducted surveillance activities. Full article

(This article belongs to the Special Issue Mosquito-Borne Virus Discovery, Diagnostics and Vaccines)

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13 pages, 5993 KiB

Open AccessArticle

Strain- and Subtype-Specific Replication of Genotype 3 Hepatitis E Viruses in Mongolian Gerbils

by Tiancheng Li, Yusuke Sakai, Yasushi Ami, Yuriko Suzaki and Masanori Isogawa

Viruses 2024, 16(10), 1605; https://doi.org/10.3390/v16101605 (registering DOI) - 12 Oct 2024

Abstract

Since Mongolian gerbils are broadly susceptible to hepatitis E virus (HEV), including genotypes 1, 4, 5, and 8 (HEV-1, HEV-5, HEV-5, and HEV-8) and rat HEV, they are a useful small animal model for HEV. However, we have observed that the subtypes HEV-3k [...] Read more.

Since Mongolian gerbils are broadly susceptible to hepatitis E virus (HEV), including genotypes 1, 4, 5, and 8 (HEV-1, HEV-5, HEV-5, and HEV-8) and rat HEV, they are a useful small animal model for HEV. However, we have observed that the subtypes HEV-3k and HEV-3ra in genotype 3 HEV (HEV-3) were not infected efficiently in the gerbils. A small-animal model for HEV-3 is also needed since HEV-3 is responsible for major zoonotic HEV infections. To investigate whether gerbils can be used as animal models for other subtypes of HEV-3, we injected gerbils with five HEV-3 subtypes (HEV-3b, -3e, -3f, -3k, and -3ra) and compared the infectivity of the subtypes. We detected viral RNA in the gerbils’ feces. High titers of anti-HEV IgG antibodies in serum were induced in all HEV-3b/ch-, HEV-3f-, and HEV-3e-injected gerbils. Especially, the HEV-3e-injected animals released high levels of viruses into their feces for an extended period. The virus replication was limited in the HEV-3b/wb-injected and HEV-3k-injected groups. Although viral RNA was detected in HEV-3ra-injected gerbils, the copy numbers in fecal specimens were low; no antibodies were detected in the sera. These results indicate that although HEV-3′s infectivity in gerbils depends on the subtype and strain, Mongolian gerbils have potential as a small-animal model for HEV-3. A further comparison of HEV-3e with different genotype strains (HEV-4i and HEV-5) and different genera (rat HEV) revealed different ALT elevations among the strains, and liver damage occurred in HEV-4i- and HEV-5-infected but not HEV-3e- or rat HEV-infected gerbils, demonstrating variable pathogenicity across HEVs from different genera and genotypes in Mongolian gerbils. HEV-4i- and HEV-5-infected Mongolian gerbils might be candidate animal models to examine HEV’s pathogenicity. Full article

(This article belongs to the Special Issue Hepatitis E: Molecular Virology, Pathogenesis, and Treatment, 2nd Edition)

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12 pages, 2092 KiB

Open AccessArticle

Utility of ISARIC 4C Mortality Score, Vaccination History, and Anti-S Antibody Titre in Predicting Risk of Severe COVID-19

by Lin Pin Koh, Travis Ren Teen Chia, Samuel Sherng Young Wang, Jean-Marc Chavatte, Robert Hawkins, Yonghan Ting, Jordan Zheng Ting Sim, Wen Xiang Chen, Kelvin Bryan Tan, Cher Heng Tan, David Chien Lye and Barnaby E. Young

Viruses 2024, 16(10), 1604; https://doi.org/10.3390/v16101604 - 12 Oct 2024

Abstract

The ISARIC 4C Mortality score was developed to predict mortality risk among patients with COVID-19. Its performance among vaccinated individuals is understudied. This is a retrospective study of all patients with SARS-CoV-2 infection admitted to the National Centre for Infectious Diseases, Singapore, from [...] Read more.

The ISARIC 4C Mortality score was developed to predict mortality risk among patients with COVID-19. Its performance among vaccinated individuals is understudied. This is a retrospective study of all patients with SARS-CoV-2 infection admitted to the National Centre for Infectious Diseases, Singapore, from January-2020 to December-2021. Demographic, clinical, and laboratory data were extracted, and multiple logistic regression (MLR) models were developed to predict the relationship between ISARIC score, vaccination status, anti-S antibody titre, and severe COVID-19. A total of 6377 patients were identified, of which 5329 met the study eligibility criteria. The median age of the patients was 47 years (IQR 35–71), 1264 (23.7%) were female, and 1239 (25.7%) were vaccinated. Severe disease occurred in 499 (9.4%) patients, including 133 (2.5%) deaths. After stratification, 3.0% of patients with low (0–4), 17.8% of patients with moderate (5–9), and 36.2% of patients with high (≥10) ISARIC scores developed severe COVID-19. Vaccination was associated with a reduced risk of progression to severe COVID-19 in the MLR model: aOR 0.88 (95% CI: 0.86–0.90), and the risk of severe COVID-19 decreased inversely to anti-S antibody titres. The anti-S antibody titre should be further investigated as an adjunct to the ISARIC score to triage COVID-19 patients for hospital admission and antiviral therapy. Full article

(This article belongs to the Special Issue COVID-19 and Pneumonia 3rd Edition)

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8 pages, 642 KiB

Open AccessCase Report

Exploring Dengue Infection in a Vaccinated Individual: Preliminary Molecular Diagnosis and Sequencing Insights

by Talita Émile Ribeiro Adelino, Sílvia Helena Sousa Pietra Pedroso, Maurício Lima, Luiz Marcelo Ribeiro Tomé, Natália Rocha Guimarães, Vagner Fonseca, Paulo Eduardo de Souza da Silva, Keldenn Melo Farias Moreno, Ana Cândida Araújo e Silva, Náthale Rodrigues Pinheiro, Carolina Senra Alves de Souza, Luiz Carlos Junior Alcantara, Marta Giovanetti and Felipe Campos de Melo Iani

Viruses 2024, 16(10), 1603; https://doi.org/10.3390/v16101603 - 12 Oct 2024

Abstract

This study examines a case involving a 7-year-old child who developed dengue symptoms following Qdenga vaccination. Despite initial negative diagnostic results, molecular analysis confirmed an infection with DENV4. Next-generation sequencing detected viral RNA from both DENV2 and DENV4 serotypes, which were identified as [...] Read more.

This study examines a case involving a 7-year-old child who developed dengue symptoms following Qdenga vaccination. Despite initial negative diagnostic results, molecular analysis confirmed an infection with DENV4. Next-generation sequencing detected viral RNA from both DENV2 and DENV4 serotypes, which were identified as vaccine-derived strains using specific primers. Phylogenetic analysis further confirmed that these sequences belonged to the Qdenga vaccine rather than circulating wild-type viruses. This case underscores the critical need for precise diagnostic interpretation in vaccinated individuals to avoid misdiagnosis and to strengthen public health surveillance. A comprehensive understanding of vaccine-induced viremia is essential for refining dengue surveillance, improving diagnostic accuracy, and informing public health strategies in endemic regions. Full article

(This article belongs to the Special Issue Molecular Epidemiology, Evolution, and Dispersion of Flaviviruses (2nd Edition))

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19 pages, 11837 KiB

Open AccessArticle

Replication Characteristics of African Swine Fever Virus (ASFV) Genotype I E70 and ASFV Genotype II Belgium 2018/1 in Perivenous Macrophages Using Established Vein Explant Model

by Shaojie Han, Dayoung Oh, Nadège Balmelle, Ann Brigitte Cay, Xiaolei Ren, Brecht Droesbeke, Marylène Tignon and Hans Nauwynck

Viruses 2024, 16(10), 1602; https://doi.org/10.3390/v16101602 - 12 Oct 2024

Abstract

African Swine Fever Virus (ASFV), resulting in strain-dependent vascular pathology, leading to hemorrhagic fever, is an important pathogen in swine. The pathogenesis of ASFV is determined by the array and spatial distribution of susceptible cells within the host. In this study, the replication [...] Read more.

African Swine Fever Virus (ASFV), resulting in strain-dependent vascular pathology, leading to hemorrhagic fever, is an important pathogen in swine. The pathogenesis of ASFV is determined by the array and spatial distribution of susceptible cells within the host. In this study, the replication characteristics of ASFV genotype I E70 (G1-E70) and ASFV genotype II Belgium 2018/1 (G2-B18) in the environment of small veins were investigated in an established vein explant model. Immunofluorescence staining analysis revealed that perivenous macrophages (CD163⁺ cells) were widely distributed in the explant, with most of them (approximately 2–10 cells/0.03 mm²) being present close to the vein (within a radius of 0–348 µm). Upon inoculation with G1-E70 and G2-B18, we observed an increase in the quantity of cells testing positive for viral antigens over time. G1-E70 replicated more efficiently than G2-B18 in the vein explants (7.6-fold for the ear explant at 72 hpi). The majority of ASFV⁺ cells were CD163⁺, indicating that macrophages are the primary target cells. Additional identification of cells infected with ASFV revealed the presence of vimentin⁺, CD14⁺, and VWF⁺ cells, demonstrating the cellular diversity and complexity associated with ASFV infection. By the use of this new vein explant model, the susceptibility of vascular and perivascular cells to an ASFV infection was identified. With this model, it will be possible now to conduct more functional analyses to get better insights into the pathogenesis of ASFV-induced hemorrhages. Full article

(This article belongs to the Section Animal Viruses)

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16 pages, 2513 KiB

Open AccessArticle

Herpes Simplex Virus Type 2 Blocks IFN-β Production through the Viral UL24 N-Terminal Domain-Mediated Inhibition of IRF-3 Phosphorylation

by Binman Zhang, Yuncheng Li, Ping Yang, Siyu He, Weilin Li, Miaomiao Li, Qinxue Hu and Mudan Zhang

Viruses 2024, 16(10), 1601; https://doi.org/10.3390/v16101601 - 11 Oct 2024

Abstract

Herpes simplex virus type 2 (HSV-2) is a sexually transmitted virus, the cause of genital herpes, and its infection can increase the risk of HIV-1 infection. After initial infection, HSV-2 can establish lifelong latency within the nervous system, which is likely associated with [...] Read more.

Herpes simplex virus type 2 (HSV-2) is a sexually transmitted virus, the cause of genital herpes, and its infection can increase the risk of HIV-1 infection. After initial infection, HSV-2 can establish lifelong latency within the nervous system, which is likely associated with the virus-mediated immune evasion. In this study, we found that HSV-2 UL24 significantly inhibited the activation of the IFN-β promoter and the production of IFN-β at both mRNA and protein levels. Of importance, the inhibitory effect of HSV-2 on IFN-β production was significantly impaired in the context of HSV-2 infection when UL24 was knocked down. Additional studies revealed that, although the full-length HSV-2 UL24 affected cell cycle and viability to some extent, its N-terminal 1–202AA domain showed no obvious cytotoxicity while its C-terminal 201–281 AA domain had a minimal impact on cell viability. Further studies showed that the N-terminal 1–202 AA domain of HSV-2 UL24 (HSV-2 UL24-N) was the main functional region responsible for the inhibition of IFN-β production mediated by HSV-2 UL24. This domain significantly suppressed the activity of RIG-IN, MAVS, TBK-1, IKK-ε, or the IRF-3/5D-activated IFN-β promoter. Mechanistically, HSV-2 UL24-N suppressed IRF-3 phosphorylation, resulting in the inhibition of IFN-β production. The findings of this study highlight the significance of HSV-2 UL24 in inhibiting IFN-β production, revealing two potential roles of UL24 during HSV-2 infection: facilitating immune evasion and inducing cell cycle arrest. Full article

(This article belongs to the Special Issue Viral Strategies to Regulate Host Immunity or Signal Pathways)

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18 pages, 11581 KiB

Open AccessArticle

Preparation and Application of Polyclonal Antibodies for the Rapid Detection of Actinidia Chlorotic Ringspot-Associated Virus

by Jing Shang, Hongping Feng, Yuxuan Wang, Yunan Wang, Xiao Zhang and Zhouyu Zhang

Viruses 2024, 16(10), 1600; https://doi.org/10.3390/v16101600 - 11 Oct 2024

Abstract

Actinidia chlorotic ringspot-associated virus (AcCRaV, Emaravirus actinidiae) is prevalent in Chinese kiwifruit, leading to substantial yield reduction. The intricate nature of symptoms presents diagnostic challenges, underscoring the necessity for a rapid and accurate detection method that facilitates effective control. In this investigation, [...] Read more.

Actinidia chlorotic ringspot-associated virus (AcCRaV, Emaravirus actinidiae) is prevalent in Chinese kiwifruit, leading to substantial yield reduction. The intricate nature of symptoms presents diagnostic challenges, underscoring the necessity for a rapid and accurate detection method that facilitates effective control. In this investigation, AcCRaV isolates from key kiwi-producing regions in Sichuan province were collected and analyzed, with representative strains chosen as experimental materials. Primers targeting the nucleoprotein gene of AcCRaV were designed, and their codon usage was optimized to enhance performance. Various serological methods utilizing polyclonal antibodies were developed, including ELISA, dot immunobinding assay, and AcCRaV-specific gold immunochromatographic bands (AcCRaV-GICS). Field samples exhibited high specificity and sensitivity when tested using these methods. Furthermore, the results obtained from a large number of field samples are consistent with those derived from RT-PCR analysis, further validating the applicability of our approach. A detection method capable of handling a large volume of field samples infected with AcCRaV is currently lacking; thus, our system construction provides an important reference for addressing this gap. Full article

(This article belongs to the Special Issue Advances in Plant Virus/Viroid Detection and Identification Methods)

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14 pages, 2141 KiB

Open AccessArticle

Higher Frequency of SARS-CoV-2 RNA Shedding by Cats than Dogs in Households with Owners Recently Diagnosed with COVID-19

by Michele Lunardi, Felippe Danyel Cardoso Martins, Emanuele Gustani-Buss, Roberta Torres Chideroli, Isabela Medeiros de Oliveira, Kamila Chagas Peronni, David Livingstone Alves Figueiredo, Alice Fernandes Alfieri and Amauri Alcindo Alfieri

Viruses 2024, 16(10), 1599; https://doi.org/10.3390/v16101599 - 11 Oct 2024

Abstract

Studies have demonstrated the susceptibility of companion animals to natural infection with SARS-CoV-2. Using quantitative reverse transcription polymerase chain reaction and sequencing analyses, this study investigated SARS-CoV-2 RNA excretion in pets in households with infected owners. Oropharyngeal and rectal swabs were collected from [...] Read more.

Studies have demonstrated the susceptibility of companion animals to natural infection with SARS-CoV-2. Using quantitative reverse transcription polymerase chain reaction and sequencing analyses, this study investigated SARS-CoV-2 RNA excretion in pets in households with infected owners. Oropharyngeal and rectal swabs were collected from dogs and cats in Parana, Southern Brazil, between October 2020 and April 2021. Viral RNA was detected in 25% of cats and 0.98% of dog oropharyngeal swabs; however, systemic, respiratory, and gastrointestinal signs were absent. Complete viral genomes belonged to the Gamma lineage. Phylogenetic analyses indicated that pet samples were probably derived from human-positive cases in Parana. Viral excretion in the oropharynx was more frequent in cats than in dogs. Mutations in the S protein characteristic of Gamma strains were present in all sequenced SARS-CoV-2 strains. The receptor-binding domain of these Brazilian strains did not show any additional mutations not reported in the Gamma strains. Mutations in NSP6, NSP12, and N proteins previously mapped to strains that infect deer or minks were detected. This study highlights the importance of actively monitoring the SARS-CoV-2 strains that infect pets with continued viral exposure. Monitoring genetic changes is crucial because new variants adapted to animals may pose human health risks. Full article

(This article belongs to the Special Issue Multiple Hosts of SARS-CoV-2: Second Volume)

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Graphical abstract

12 pages, 233 KiB

Open AccessEditorial

Viroids and Satellites and Their Vector Interactions—This Special Issue Is Dedicated to the Memory of Theodor O. Diener Who Discovered Viroids

by Ahmed Hadidi, Henryk H. Czosnek, Kriton Kalantidis and Peter Palukaitis

Viruses 2024, 16(10), 1598; https://doi.org/10.3390/v16101598 - 11 Oct 2024

Abstract

Many diseases of unknown etiology with symptoms like those caused by plant viruses but for which no virions could be found were described during the early and mid-20th century [...] Full article

(This article belongs to the Special Issue Viroids and Satellites and Their Vector Interactions—This Special Issue Is Dedicated to the Memory of Theodor O. Diener Who Discovered Viroids)

17 pages, 3922 KiB

Open AccessArticle

Frequency of Major Transmitted Integrase Resistance in Poland Remains Low Despite Change in Subtype Variability

by Kaja Mielczak, Karol Serwin, Anna Urbańska, Bogusz Aksak-Wąs, Malwina Karasińska-Cieślak, Elżbieta Mularska, Adam Witor, Paweł Jakubowski, Maria Hlebowicz, Monika Bociąga-Jasik, Elżbieta Jabłonowska, Aleksandra Szymczak, Bartosz Szetela, Władysław Łojewski and Miłosz Parczewski

Viruses 2024, 16(10), 1597; https://doi.org/10.3390/v16101597 - 11 Oct 2024

Abstract

With the widespread use of integrase inhibitors and the expanding use of long-acting cabotegravir in both pre-exposure prophylaxis and antiretroviral treatment, molecular surveillance on the transmission of integrase resistance has regained clinical significance. This study aimed to determine the frequency of INSTI-transmitted drug [...] Read more.

With the widespread use of integrase inhibitors and the expanding use of long-acting cabotegravir in both pre-exposure prophylaxis and antiretroviral treatment, molecular surveillance on the transmission of integrase resistance has regained clinical significance. This study aimed to determine the frequency of INSTI-transmitted drug resistance mutations (DRMs) among treatment-naïve individuals in Poland from 2016 to 2023. INSTI resistance was analyzed in 882 antiretroviral treatment-naïve individuals using Sanger sequencing. Integrase DRMs were defined based on the Stanford HIV drug resistance database scores. Phylogeny was used to investigate subtyping and clustering. For the analysis of time-trends, logistic regression was used. Major (E138K and R263K) integrase mutations were detected in 0.45% of cases with minor resistance observed in 14.85%, most commonly (13.95%) E157Q. Overall, no major clusters of transmitted drug resistance were identified, and the transmission of E157Q showed a decreasing trend (p < 0.001). While the frequency of sub-subtype A6 increased, it was predominantly found among migrants and associated with L74 mutations. The frequency of major integrase-transmitted DRMs remains low, despite the changes in subtype variability. Surveillance of changing HIV molecular variation patterns is vital from the perspective of the optimal use of integrase inhibitors, especially due to expanding long-acting cabotegravir implementation. Full article

(This article belongs to the Special Issue Antiviral Drugs and Biologics Targeting HIV: Drug Resistance to Newer Treatment and Pre-Exposure Prophylaxis (PrEP) Options)

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