Journal Description
Viruses
Viruses
is a peer-reviewed, open access journal of virology, published monthly online by MDPI. The American Society for Virology (ASV), Spanish Society for Virology (SEV), Canadian Society for Virology (CSV), Italian Society for Virology (SIV-ISV), Australasian Virology Society (AVS) and others are affiliated with Viruses and their members receive a discount on the article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, MEDLINE, PMC, Embase, PubAg, AGRIS, and other databases.
- Journal Rank: JCR - Q2 (Virology) / CiteScore - Q1 (Infectious Diseases)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 16.1 days after submission; acceptance to publication is undertaken in 2.6 days (median values for papers published in this journal in the first half of 2024).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Companion journal: Zoonotic Diseases.
Impact Factor:
3.8 (2023);
5-Year Impact Factor:
4.0 (2023)
Latest Articles
Differing Transcriptomic Responses in High Titer versus Low Titer Aedes aegypti Mosquitoes after Oral Infection with Sindbis Virus
Viruses 2024, 16(9), 1487; https://doi.org/10.3390/v16091487 (registering DOI) - 19 Sep 2024
Abstract
Oral infection of mosquitoes by arboviruses often results in a large degree of variation in the amount of infectious virus between individual mosquitoes, even when the mosquitoes are from inbred laboratory strains. This variability in arbovirus load has been shown to affect virus
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Oral infection of mosquitoes by arboviruses often results in a large degree of variation in the amount of infectious virus between individual mosquitoes, even when the mosquitoes are from inbred laboratory strains. This variability in arbovirus load has been shown to affect virus transmissibility. Previously, our group described population genetic and specific infectivity differences between the virus populations found in high and low titer Aedes aegypti mosquitoes that had been orally infected with Sindbis virus (SINV). In this study, we sought to investigate whether there were also differences in transcriptomic response between these high and low titer mosquitoes. Results from the transcriptomic data analysis showed that more genes involved in antiviral activity, endopeptidase activity, and methyltransferase activity were upregulated in low titer mosquitoes than in high titer mosquitoes, relative to blood-fed controls. Meanwhile, genes involved in ion transport, energy metabolism, acetylation, glycosylation, lipid metabolism, and transport tended to be upregulated in high titer mosquitoes more than in low titer mosquitoes, relative to blood-fed mosquitoes. Overall, genes involved in antiviral activities tended to be upregulated in low titer mosquitoes while genes involved in proviral activities were mostly upregulated in high titer mosquitoes. This study has identified a number of candidate mosquito genes that are putatively associated with SINV titer variability after oral infection of Ae. aegypti, and these can now be investigated in order to ascertain their roles in virus replication and their contributions to determining vector competence.
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(This article belongs to the Section Invertebrate Viruses)
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Extensive Diversity of Viruses in Millipedes Collected in the Dong Nai Biosphere Reserve (Vietnam)
by
Alexander G. Litov, Irina I. Semenyuk, Oxana A. Belova, Alexandra E. Polienko, Nguyen Van Thinh, Galina G. Karganova and Alexei V. Tiunov
Viruses 2024, 16(9), 1486; https://doi.org/10.3390/v16091486 - 19 Sep 2024
Abstract
Advances in sequencing technologies and bioinformatics have led to breakthroughs in the study of virus biodiversity. Millipedes (Diplopoda, Myriapoda, Arthropoda) include more than 12,000 extant species, yet data on virus diversity in Diplopoda are scarce. This study aimed to explore the virome of
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Advances in sequencing technologies and bioinformatics have led to breakthroughs in the study of virus biodiversity. Millipedes (Diplopoda, Myriapoda, Arthropoda) include more than 12,000 extant species, yet data on virus diversity in Diplopoda are scarce. This study aimed to explore the virome of the millipedes collected in the Dong Nai Biosphere Reserve in Vietnam. We studied 14 species of millipedes and managed to assemble and annotate the complete coding genomes of 16 novel viruses, the partial coding genomes of 10 more viruses, and several fragmented viral sequences, which may indicate the presence of about 54 more viruses in the studied samples. Among the complete and partial genomes, 27% were putative members of the order Picornavirales. Most of the discovered viruses were very distant from the viruses currently present in the relevant databases. At least eight viruses meet the criteria to be recognized as a new species by the International Committee on Taxonomy of Viruses, and, for two of them, a higher taxonomic status (genus and even family) can be suggested.
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(This article belongs to the Section Invertebrate Viruses)
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Hepatocellular Carcinoma Incidences and Risk Factors in Hepatitis C Patients: Interferon Versus Direct-Acting Agents
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Yu-Ting Kao, Yen-Chun Liu, Ya-Ting Cheng, Yu-Wen Wen, Yi-Chung Hsieh, Cheng-Er Hsu, Chung-Wei Su, Jennifer Chia-Hung Tai, Yi-Cheng Chen, Wen-Juei Jeng, Chun-Yen Lin, Rong-Nan Chien, Dar-In Tai and I-Shyan Sheen
Viruses 2024, 16(9), 1485; https://doi.org/10.3390/v16091485 - 18 Sep 2024
Abstract
Background: Hepatocellular carcinoma (HCC) remains a significant concern for patients with chronic hepatitis C (HCV), even after achieving a sustained virological response (SVR) with direct-acting antivirals (DAAs) or interferon (IFN)-based therapies. This study compared the risk of HCC in patients with HCV who
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Background: Hepatocellular carcinoma (HCC) remains a significant concern for patients with chronic hepatitis C (HCV), even after achieving a sustained virological response (SVR) with direct-acting antivirals (DAAs) or interferon (IFN)-based therapies. This study compared the risk of HCC in patients with HCV who achieved SVR through the DAA versus IFN regimens. Methods: A retrospective analysis was conducted on 4806 HCV patients, without coinfection nor prior HCC history, treated at the Chang Gung Memorial Hospital, Taiwan (DAA: 2825, IFN: 1981). Kaplan–Meier and Cox regression analyses with propensity score matching (PSM) were used to adjust for baseline differences. Results: DAA-treated patients exhibited a higher incidence of HCC than IFN-treated patients before and after PSM (after PSM: annual: 1% vs. 0.5%; 6-year: 6% vs. 3%, p = 0.01). Both DAA and IFN patients had a decreased HCC incidence during follow-up (>3 vs. <3 years from the end of treatment: DAA: 1.43% vs. 1.00% per year; IFN: 0.47% vs. 0.36% per year, both p < 0.05). HCC incidence was higher in the first three years post-SVR in DAA-treated ACLD patients and then decreased (3.26% vs. 1.39% per year, p < 0.01). In contrast, HCC incidence remained constant in the non-ACLD and IFN-treated groups. Multivariate Cox regression identified age ≥ 60, male sex, BMI, AFP ≥ 6 ng/mL, FIB-4, and ACLD status as independent risk factors for HCC, but antiviral regimens were not an independent factor for HCC. Conclusion: DAA treatment significantly affects HCC risk primarily within three years post-treatment, especially in younger HCV patients with ACLD. HCC incidence was reduced after three years in ACLD patients treated by DAA, but continued surveillance was still necessary. However, patients under 60 without advanced liver disease may require less intensive follow-up.
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(This article belongs to the Section Human Virology and Viral Diseases)
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Open AccessReview
New Therapies and Strategies to Curb HIV Infections with a Focus on Macrophages and Reservoirs
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Maria Marra, Alessia Catalano, Maria Stefania Sinicropi, Jessica Ceramella, Domenico Iacopetta, Romina Salpini, Valentina Svicher, Stefania Marsico, Stefano Aquaro and Michele Pellegrino
Viruses 2024, 16(9), 1484; https://doi.org/10.3390/v16091484 - 18 Sep 2024
Abstract
More than 80 million people worldwide have been infected with the human immunodeficiency virus (HIV). There are now approximately 39 million individuals living with HIV/acquired immunodeficiency syndrome (AIDS). Although treatments against HIV infection are available, AIDS remains a serious disease. Combination antiretroviral therapy
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More than 80 million people worldwide have been infected with the human immunodeficiency virus (HIV). There are now approximately 39 million individuals living with HIV/acquired immunodeficiency syndrome (AIDS). Although treatments against HIV infection are available, AIDS remains a serious disease. Combination antiretroviral therapy (cART), also known as highly active antiretroviral therapy (HAART), consists of treatment with a combination of several antiretroviral drugs that block multiple stages in the virus replication cycle. However, the increasing usage of cART is inevitably associated with the emergence of HIV drug resistance. In addition, the development of persistent cellular reservoirs of latent HIV is a critical obstacle to viral eradication since viral rebound takes place once anti-retroviral therapy (ART) is interrupted. Thus, several efforts are being applied to new generations of drugs, vaccines and new types of cART. In this review, we summarize the antiviral therapies used for the treatment of HIV/AIDS, both as individual agents and as combination therapies, and highlight the role of both macrophages and HIV cellular reservoirs and the most recent clinical studies related to this disease.
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(This article belongs to the Special Issue Roles of Macrophages in Viral Infections)
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Mycologists and Virologists Align: Proposing Botrytis cinerea for Global Mycovirus Studies
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Mahmoud E. Khalifa, María A. Ayllón, Lorena Rodriguez Coy, Kim M. Plummer, Anthony R. Gendall, Kar Mun Chooi, Jan A.L. van Kan and Robin M. MacDiarmid
Viruses 2024, 16(9), 1483; https://doi.org/10.3390/v16091483 - 18 Sep 2024
Abstract
Mycoviruses are highly genetically diverse and can significantly change their fungal host’s phenotype, yet they are generally under-described in genotypic and biological studies. We propose Botrytis cinerea as a model mycovirus system in which to develop a deeper understanding of mycovirus epidemiology including
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Mycoviruses are highly genetically diverse and can significantly change their fungal host’s phenotype, yet they are generally under-described in genotypic and biological studies. We propose Botrytis cinerea as a model mycovirus system in which to develop a deeper understanding of mycovirus epidemiology including diversity, impact, and the associated cellular biology of the host and virus interaction. Over 100 mycoviruses have been described in this fungal host. B. cinerea is an ideal model fungus for mycovirology as it has highly tractable characteristics—it is easy to culture, has a worldwide distribution, infects a wide range of host plants, can be transformed and gene-edited, and has an existing depth of biological resources including annotated genomes, transcriptomes, and isolates with gene knockouts. Focusing on a model system for mycoviruses will enable the research community to address deep research questions that cannot be answered in a non-systematic manner. Since B. cinerea is a major plant pathogen, new insights may have immediate utility as well as creating new knowledge that complements and extends the knowledge of mycovirus interactions in other fungi, alone or with their respective plant hosts. In this review, we set out some of the critical steps required to develop B. cinerea as a model mycovirus system and how this may be used in the future.
Full article
(This article belongs to the Special Issue Diversity and Coinfections of Plant or Fungal Viruses, 3rd Edition)
Open AccessArticle
The Autonomous Fusion Activity of Human Cytomegalovirus Glycoprotein B Is Regulated by Its Carboxy-Terminal Domain
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Nina Reuter, Barbara Kropff, Xiaohan Chen, William J. Britt, Heinrich Sticht, Michael Mach and Marco Thomas
Viruses 2024, 16(9), 1482; https://doi.org/10.3390/v16091482 - 18 Sep 2024
Abstract
The human cytomegalovirus (HCMV) glycoprotein B (gB) is the viral fusogen required for entry into cells and for direct cell-to-cell spread of the virus. We have previously demonstrated that the exchange of the carboxy-terminal domain (CTD) of gB for the CTD of the
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The human cytomegalovirus (HCMV) glycoprotein B (gB) is the viral fusogen required for entry into cells and for direct cell-to-cell spread of the virus. We have previously demonstrated that the exchange of the carboxy-terminal domain (CTD) of gB for the CTD of the structurally related fusion protein G of the vesicular stomatitis virus (VSV-G) resulted in an intrinsically fusion-active gB variant (gB/VSV-G). In this present study, we employed a dual split protein (DSP)-based cell fusion assay to further characterize the determinants of fusion activity in the CTD of gB. We generated a comprehensive library of gB CTD truncation mutants and identified two mutants, gB-787 and gB-807, which were fusion-competent and induced the formation of multinucleated cell syncytia in the absence of other HCMV proteins. Structural modeling coupled with site-directed mutagenesis revealed that gB fusion activity is primarily mediated by the CTD helix 2, and secondarily by the recruitment of cellular SH2/WW-domain-containing proteins. The fusion activity of gB-807 was inhibited by gB-specific monoclonal antibodies (MAbs) targeting the antigenic domains AD-1 to AD-5 within the ectodomain and not restricted to MAbs directed against AD-4 and AD-5 as observed for gB/VSV-G. This finding suggested a differential regulation of the fusion-active conformational state of both gB variants. Collectively, our findings underscore a pivotal role of the CTD in regulating the fusogenicity of HCMV gB, with important implications for understanding the conformations of gB that facilitate membrane fusion, including antigenic structures that could be targeted by antibodies to block this essential step in HCMV infection.
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(This article belongs to the Special Issue Research on Herpes Virus Fusion and Entry)
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Immunogenicity of an Inactivated COVID-19 Vaccine in People Living with HIV in Guangxi, China: A Prospective Cohort Study
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Yuting Wu, Xinwei Wang, Yunxuan Huang, Rongfeng Chen, Yuexiang Xu, Wudi Wei, Fengxiang Qin, Zongxiang Yuan, Jinming Su, Xiu Chen, Jie Liu, Liufang Wen, Minjuan Shi, Tongxue Qin, Yinlu Liao, Beibei Lu, Xing Tao, Cuixiao Wang, Shanshan Chen, Jinmiao Li, William J. Liu, Li Ye, Hao Liang and Junjun Jiangadd
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Viruses 2024, 16(9), 1481; https://doi.org/10.3390/v16091481 - 18 Sep 2024
Abstract
The inactivated COVID-19 vaccine has demonstrated high efficacy in the general population through extensive clinical and real-world studies. However, its effectiveness in immunocompromised individuals, particularly those living with HIV (PLWH), remains limited. In this study, 20 PLWH and 15 HIV-seronegative individuals were recruited
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The inactivated COVID-19 vaccine has demonstrated high efficacy in the general population through extensive clinical and real-world studies. However, its effectiveness in immunocompromised individuals, particularly those living with HIV (PLWH), remains limited. In this study, 20 PLWH and 15 HIV-seronegative individuals were recruited to evaluate the immunogenicity of an inactivated COVID-19 vaccine in PLWH through a prospective cohort study. The median age of the 20 PLWH and 15 HIV-seronegative individuals was 42 years and 31 years, respectively. Of the PLWH, nine had been on ART for over five years. The median anti-SARS-CoV-2 S-RBD IgG antibody level on d224 was higher than that on d42 (8188.7 ng/mL vs. 3200.9 ng/mL, P < 0.05). Following COVID-19 infection, the antibody level increased to 29,872.5 ng/mL on dre+90, 12.19 times higher than that on d300. Compared with HIV-seronegative individuals, the antibody level in PLWH was lower on d210 (183.3 ng/mL vs. 509.3 ng/mL, P < 0.01), while there was no difference after d224. The symptoms of COVID-19 infection in PLWH were comparable to those in HIV-seronegative individuals. In this study, the inactivated COVID-19 vaccine demonstrated good immunogenicity in PLWH. The protective benefit of booster vaccinations for PLWH cannot be ignored. Implementing a booster vaccination policy for PLWH is an effective approach to providing better protection against the COVID-19 pandemic.
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(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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Sputnik V-Induced Antibodies against SARS-CoV-2 Variants during the Dissemination of the Gamma Variant in Venezuela
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Christopher Franco, Alejandro Cornejo, Mariajosé Rodríguez, Alexis García, Inirida Belisario, Soriuska Mayora, Domingo José Garzaro, Rossana Celeste Jaspe, Mariana Hidalgo, Nereida Parra, Ferdinando Liprandi, José Luis Zambrano, Héctor Rafael Rangel and Flor Helene Pujol
Viruses 2024, 16(9), 1480; https://doi.org/10.3390/v16091480 - 18 Sep 2024
Abstract
The COVID-19 pandemic was characterized by the emergence and succession of SARS-CoV-2 variants able to evade the antibody response induced by natural infection and vaccination. To evaluate the IgG reactivity and neutralizing capacity of the serum of individuals vaccinated with Sputnik V (105
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The COVID-19 pandemic was characterized by the emergence and succession of SARS-CoV-2 variants able to evade the antibody response induced by natural infection and vaccination. To evaluate the IgG reactivity and neutralizing capacity of the serum of individuals vaccinated with Sputnik V (105 volunteers vaccinated) against different viral variants. IgG reactivity to the Spike protein (S) was evaluated by ELISA. A plaque reduction neutralization test was performed using different viral variant isolates. At 42 days post-vaccination, the frequency of recognition and reactivity to the S protein of the Omicron variant was lower compared to that of the other variants. In general, a higher average neutralization titer was seen against the ancestral variant compared to the variants, especially Omicron. However, some sera exhibited a higher neutralization titer to the Gamma variant compared to the ancestral variant, suggesting unapparent exposure during the clinical trial. Antibodies induced by Sputnik V can recognize, persist, and neutralize SARS-CoV-2 variants, with Omicron being the one that best evades this response. These results represent a unique report on the humoral response induced by a globally lesser-studied vaccine in terms of efficacy and immune escape, offering insights into developing vaccines targeting unknown coronaviruses.
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(This article belongs to the Special Issue Host Cell-Virus Interaction, 3rd Edition)
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Open AccessBrief Report
The Discovery of a Citrus Yellow Vein Clearing Virus Hacienda Heights Isolate Diversifies the Geological Origins of the Virus in California, United States
by
Yong-Duo Sun and Raymond Yokomi
Viruses 2024, 16(9), 1479; https://doi.org/10.3390/v16091479 - 18 Sep 2024
Abstract
The citrus yellow vein clearing virus (CYVCV) is an emerging threat to the U.S. citrus industry. Reports from China shows it cause significant reductions in fruit yield and growth, particularly in lemon trees. In 2022, CYVCV was detected in a wide range of
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The citrus yellow vein clearing virus (CYVCV) is an emerging threat to the U.S. citrus industry. Reports from China shows it cause significant reductions in fruit yield and growth, particularly in lemon trees. In 2022, CYVCV was detected in a wide range of citrus cultivars in localized urban properties in Tulare, California. In 2024, a CYVCV-infected lemon tree was detected in Hacienda Heights in Los Angeles County, California, geographically separated from the Tulare foci. Through long-read sequencing technology, the whole-genome sequence of a CYVCV isolate from Hacienda Heights (designated as CYVCV-CA-HH1, Accession number PP840891.1) was obtained. Sequence alignments and neighbornet analysis strongly suggested that the CYVCV-CA-HH1 isolate has a different origin than the Tulare CYVCV (CYVCV CA-TL) isolates. The CYVCV CA-TL isolates were grouped with those from South Asia (India and Pakistan) and the Middle East (Türkiye), while the CYVCV-CA-HH1 isolate was grouped with isolates from East Asia (China and South Korea). Maximum likelihood phylogenetic analysis further supports this finding, showing that the CYVCV-CA-HH1 isolate shares the most recent common ancestor with a South Korean lineage, which derives from Chinese isolates. Together, our data suggest a diverse geological origin of CYVCV isolates in California.
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(This article belongs to the Special Issue Emerging Fruit and Vegetable Viruses 2023)
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Insights into the Role of VPS39 and Its Interaction with CP204L and A137R in ASFV Infection
by
Katarzyna Magdalena Dolata and Axel Karger
Viruses 2024, 16(9), 1478; https://doi.org/10.3390/v16091478 - 17 Sep 2024
Abstract
The African swine fever virus (ASFV) is a large and complex DNA virus that causes a highly lethal disease in swine, for which no antiviral drugs or vaccines are currently available. Studying viral–host protein–protein interactions advances our understanding of the molecular mechanisms underlying
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The African swine fever virus (ASFV) is a large and complex DNA virus that causes a highly lethal disease in swine, for which no antiviral drugs or vaccines are currently available. Studying viral–host protein–protein interactions advances our understanding of the molecular mechanisms underlying viral replication and pathogenesis and can facilitate the discovery of antiviral therapeutics. In this study, we employed affinity tagging and purification mass spectrometry to characterize the interactome of VPS39, an important cellular factor during the early phase of ASFV replication. The interaction network of VPS39 revealed associations with mitochondrial proteins involved in membrane contact sites formation and cellular respiration. We show that the ASFV proteins CP204L and A137R target VPS39 by interacting with its clathrin heavy-chain functional domain. Furthermore, we elaborate on the potential mechanisms by which VPS39 may contribute to ASFV replication and prioritize interactions for further investigation into mitochondrial protein function in the context of ASFV infection.
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(This article belongs to the Special Issue African Swine Fever Virus 4.0)
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Identification and Characterization of Novel Serpentoviruses in Viperid and Elapid Snakes
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Steven B. Tillis, Sarah B. Chaney, Esther E. V. Crouch, Donal Boyer, Kevin Torregrosa, Avishai D. Shuter, Anibal Armendaris, April L. Childress, Denise McAloose, Jean A. Paré, Robert J. Ossiboff and Kenneth J. Conley
Viruses 2024, 16(9), 1477; https://doi.org/10.3390/v16091477 - 17 Sep 2024
Abstract
Viruses in the subfamily Serpentovirinae (order Nidovirales, family Tobaniviridae) can cause significant morbidity and mortality in captive snakes, but documented infections have been limited to snakes of the Boidae, Colubridae, Homalopsidae, and Pythonidae families. Infections can either be
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Viruses in the subfamily Serpentovirinae (order Nidovirales, family Tobaniviridae) can cause significant morbidity and mortality in captive snakes, but documented infections have been limited to snakes of the Boidae, Colubridae, Homalopsidae, and Pythonidae families. Infections can either be subclinical or associated with oral and/or respiratory disease. Beginning in June 2019, a population of over 150 confiscated snakes was screened for serpentovirus as part of a quarantine disease investigation. Antemortem oropharyngeal swabs or lung tissue collected postmortem were screened for serpentovirus by PCR, and 92/165 (56.0%) of snakes tested were positive for serpentovirus. Serpentoviruses were detected in fourteen species of Viperidae native to Asia, Africa, and South America and a single species of Elapidae native to Australia. When present, clinical signs included thin body condition, abnormal behavior or breathing, stomatitis, and/or mortality. Postmortem findings included variably severe inflammation, necrosis, and/or epithelial proliferation throughout the respiratory and upper gastrointestinal tracts. Genetic characterization of the detected serpentoviruses identified four unique viral clades phylogenetically distinct from recognized serpentovirus genera. Pairwise uncorrected distance analysis supported the phylogenetic analysis and indicated that the viper serpentoviruses likely represent the first members of a novel genus in the subfamily Serpentovirinae. The reported findings represent the first documentation of serpentoviruses in venomous snakes (Viperidae and Elapidae), greatly expanding the susceptible host range for these viruses and highlighting the importance of serpentovirus screening in all captive snake populations.
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(This article belongs to the Special Issue Virus Discovery, Classification and Characterization)
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Toward the Eradication of Herpes Simplex Virus: Vaccination and Beyond
by
Jane Y. Chang, Curt Balch and Hyung Suk Oh
Viruses 2024, 16(9), 1476; https://doi.org/10.3390/v16091476 - 17 Sep 2024
Abstract
Herpes simplex virus (HSV) has coevolved with Homo sapiens for over 100,000 years, maintaining a tenacious presence by establishing lifelong, incurable infections in over half the human population. As of 2024, an effective prophylactic or therapeutic vaccine for HSV remains elusive. In this
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Herpes simplex virus (HSV) has coevolved with Homo sapiens for over 100,000 years, maintaining a tenacious presence by establishing lifelong, incurable infections in over half the human population. As of 2024, an effective prophylactic or therapeutic vaccine for HSV remains elusive. In this review, we independently screened PubMed, EMBASE, Medline, and Google Scholar for clinically relevant articles on HSV vaccines. We identified 12 vaccines from our literature review and found promising candidates across various classes, including subunit vaccines, live vaccines, DNA vaccines, and mRNA vaccines. Notably, several vaccines—SL-V20, HF10, VC2, and mRNA-1608—have shown promising preclinical results, suggesting that an effective HSV vaccine may be within reach. Additionally, several other vaccines such as GEN-003 (a subunit vaccine from Genocea), HerpV (a subunit vaccine from Agenus), 0ΔNLS/RVx201 (a live-attenuated replication-competent vaccine from Rational Vaccines), HSV 529 (a replication-defective vaccine from Sanofi Pasteur), and COR-1 (a DNA-based vaccine from Anteris Technologies) have demonstrated potential in clinical trials. However, GEN-003 and HerpV have not advanced further despite promising results. Continued progress with these candidates brings us closer to a significant breakthrough in preventing and treating HSV infections.
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(This article belongs to the Special Issue Molecular Mechanisms and Clinical Manifestations of Persistent Viral Infections)
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Tuning VSV-G Expression Improves Baculovirus Integrity, Stability and Mammalian Cell Transduction Efficiency
by
Martina Mattioli, Renata A. Raele, Gunjan Gautam, Ufuk Borucu, Christiane Schaffitzel, Francesco Aulicino and Imre Berger
Viruses 2024, 16(9), 1475; https://doi.org/10.3390/v16091475 - 17 Sep 2024
Abstract
Baculoviral vectors (BVs) derived from Autographa californica multiple nucleopolyhedrovirus (AcMNPV) are an attractive tool for multigene delivery in mammalian cells, which is particularly relevant for CRISPR technologies. Most applications in mammalian cells rely on BVs that are pseudotyped with vesicular stomatitis virus G-protein
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Baculoviral vectors (BVs) derived from Autographa californica multiple nucleopolyhedrovirus (AcMNPV) are an attractive tool for multigene delivery in mammalian cells, which is particularly relevant for CRISPR technologies. Most applications in mammalian cells rely on BVs that are pseudotyped with vesicular stomatitis virus G-protein (VSV-G) to promote efficient endosomal release. VSV-G expression typically occurs under the control of the hyperactive polH promoter. In this study, we demonstrate that polH-driven VSV-G expression results in BVs characterised by reduced stability, impaired morphology, and VSV-G induced toxicity at high multiplicities of transduction (MOTs) in target mammalian cells. To overcome these drawbacks, we explored five alternative viral promoters with the aim of optimising VSV-G levels displayed on the pseudotyped BVs. We report that Orf-13 and Orf-81 promoters reduce VSV-G expression to less than 5% of polH, rescuing BV morphology and stability. In a panel of human cell lines, we elucidate that BVs with reduced VSV-G support efficient gene delivery and CRISPR-mediated gene editing, at levels comparable to those obtained previously with polH VSV-G-pseudotyped BVs (polH VSV-G BV). These results demonstrate that VSV-G hyperexpression is not required for efficient transduction of mammalian cells. By contrast, reduced VSV-G expression confers similar transduction dynamics while substantially improving BV integrity, structure, and stability.
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(This article belongs to the Special Issue Baculovirus as Vaccine Vectors, RNA Interference Mediators, and Gene Delivery Vectors)
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Open AccessArticle
Increased Virulence of Culicoides Midge Cell-Derived Bluetongue Virus in IFNAR Mice
by
Barbara S. Drolet, Lindsey Reister-Hendricks, Christie Mayo, Case Rodgers, David C. Molik and David Scott McVey
Viruses 2024, 16(9), 1474; https://doi.org/10.3390/v16091474 - 17 Sep 2024
Abstract
Bluetongue (BT) is a Culicoides midge-borne hemorrhagic disease affecting cervids and ruminant livestock species, resulting in significant economic losses from animal production and trade restrictions. Experimental animal infections using the α/β interferon receptor knockout IFNAR mouse model and susceptible target species are critical
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Bluetongue (BT) is a Culicoides midge-borne hemorrhagic disease affecting cervids and ruminant livestock species, resulting in significant economic losses from animal production and trade restrictions. Experimental animal infections using the α/β interferon receptor knockout IFNAR mouse model and susceptible target species are critical for understanding viral pathogenesis, virulence, and evaluating vaccines. However, conducting experimental vector-borne transmission studies with the vector itself are logistically difficult and experimentally problematic. Therefore, experimental infections are induced by hypodermic injection with virus typically derived from baby hamster kidney (BHK) cells. Unfortunately, for many U.S. BTV serotypes, it is difficult to replicate the severity of the disease seen in natural, midge-transmitted infections by injecting BHK-derived virus into target host animals. Using the IFNAR BTV murine model, we compared the virulence of traditional BHK cell-derived BTV-17 with C. sonorensis midge (W8) cell-derived BTV-17 to determine whether using cells of the transmission vector would provide an in vitro virulence aspect of vector-transmitted virus. At both low and high doses, mice inoculated with W8-BTV-17 had an earlier onset of viremia, earlier onset and peak of clinical signs, and significantly higher mortality compared to mice inoculated with BHK-BTV-17. Our results suggest using a Culicoides W8 cell-derived inoculum may provide an in vitro vector-enhanced infection to more closely represent disease levels seen in natural midge-transmitted infections while avoiding the logistical and experimental complexity of working with live midges.
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(This article belongs to the Special Issue Bluetongue, Epizootic Haemorrhagic Disease, and Other Emerging Orbiviruses)
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Multiplex Microscopy Assay for Assessment of Therapeutic and Serum Antibodies against Emerging Pathogens
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Nuno Sartingen, Vanessa Stürmer, Matthias Kaltenböck, Thorsten G. Müller, Paul Schnitzler, Anna Kreshuk, Hans-Georg Kräusslich, Uta Merle, Frauke Mücksch, Barbara Müller, Constantin Pape and Vibor Laketa
Viruses 2024, 16(9), 1473; https://doi.org/10.3390/v16091473 - 17 Sep 2024
Abstract
The emergence of novel pathogens, exemplified recently by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), highlights the need for rapidly deployable and adaptable diagnostic assays to assess their impact on human health and guide public health responses in future pandemics. In this
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The emergence of novel pathogens, exemplified recently by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), highlights the need for rapidly deployable and adaptable diagnostic assays to assess their impact on human health and guide public health responses in future pandemics. In this study, we developed an automated multiplex microscopy assay coupled with machine learning-based analysis for antibody detection. To achieve multiplexing and simultaneous detection of multiple viral antigens, we devised a barcoding strategy utilizing a panel of HeLa-based cell lines. Each cell line expressed a distinct viral antigen, along with a fluorescent protein exhibiting a unique subcellular localization pattern for cell classification. Our robust, cell segmentation and classification algorithm, combined with automated image acquisition, ensured compatibility with a high-throughput approach. As a proof of concept, we successfully applied this approach for quantitation of immunoreactivity against different variants of SARS-CoV-2 spike and nucleocapsid proteins in sera of patients or vaccinees, as well as for the study of selective reactivity of monoclonal antibodies. Importantly, our system can be rapidly adapted to accommodate other SARS-CoV-2 variants as well as any antigen of a newly emerging pathogen, thereby representing an important resource in the context of pandemic preparedness.
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(This article belongs to the Special Issue Microscopy Methods for Virus Research)
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Breaking Latent Infection: How ORF37/38-Deletion Mutants Offer New Hope against EHV-1 Neuropathogenicity
by
Yue Hu, Si-Yu Zhang, Wen-Cheng Sun, Ya-Ru Feng, Hua-Rui Gong, Duo-Liang Ran, Bao-Zhong Zhang and Jian-Hua Liu
Viruses 2024, 16(9), 1472; https://doi.org/10.3390/v16091472 - 16 Sep 2024
Abstract
Equid alphaherpesvirus 1 (EHV-1) has been linked to the emergence of neurological disorders, with the horse racing industry experiencing significant impacts from outbreaks of equine herpesvirus myeloencephalopathy (EHM). Building robust immune memory before pathogen exposure enables rapid recognition and elimination, preventing infection. This
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Equid alphaherpesvirus 1 (EHV-1) has been linked to the emergence of neurological disorders, with the horse racing industry experiencing significant impacts from outbreaks of equine herpesvirus myeloencephalopathy (EHM). Building robust immune memory before pathogen exposure enables rapid recognition and elimination, preventing infection. This is crucial for effectively managing EHV-1. Removing neuropathogenic factors and immune evasion genes to develop live attenuated vaccines appears to be a successful strategy for EHV-1 vaccines. We created mutant viruses without ORF38 and ORF37/38 and validated their neuropathogenicity and immunogenicity in hamsters. The ∆ORF38 strain caused brain tissue damage at high doses, whereas the ∆ORF37/38 strain did not. Dexamethasone was used to confirm latent herpesvirus infection and reactivation. Dexamethasone injection increased viral DNA load in the brains of hamsters infected with the parental and ∆ORF38 strains, but not in those infected with the ∆ORF37/38 strain. Immunizing hamsters intranasally with the ∆ORF37/38 strain as a live vaccine produced a stronger immune response compared to the ∆ORF38 strain at the same dose. The hamsters demonstrated effective protection against a lethal challenge with the parental strain. This suggests that the deletion of ORF37/38 may effectively inhibit latent viral infection, reduce the neuropathogenicity of EHV-1, and induce a protective immune response.
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(This article belongs to the Section Animal Viruses)
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Epithelial Antimicrobial Peptide/Protein and Cytokine Expression Profiles Obtained from Nasopharyngeal Swabs of SARS-CoV-2-Infected and Non-Infected Subjects
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Thilo Gambichler, Silke Goesmann, Marina Skrygan, Laura Susok, Christian Schütte, Nahza Hamdani and Wolfgang Schmidt
Viruses 2024, 16(9), 1471; https://doi.org/10.3390/v16091471 - 15 Sep 2024
Abstract
Immune responses of the epithelia of the upper respiratory tract are likely crucial in early inhibition of the viral replication and finally clearance of SARS-CoV-2. We aimed to compare the expression profiles of antimicrobial peptides/proteins (AMPs) and related cytokines observed in the nasopharynx
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Immune responses of the epithelia of the upper respiratory tract are likely crucial in early inhibition of the viral replication and finally clearance of SARS-CoV-2. We aimed to compare the expression profiles of antimicrobial peptides/proteins (AMPs) and related cytokines observed in the nasopharynx of SARS-CoV-2-infected patients and non-infected controls and to assess the associations between these parameters and COVID-19 patients’ outcomes. We included 45 subjects who had tested positive for SARS-CoV-2 and 22 control subjects who had tested negative for SARS-CoV-2. Biomaterial for SARS-CoV-2 detection, as well as gene and protein expression studies, was obtained from all subjects using nasopharyngeal swabs which were performed a maximum of 7 days before inclusion in the study. Univariable and multivariable statistics were performed. When compared to the controls, the mRNA expression levels of human β-defensin 1 (hBD-1), LL-37, and trappin-2 were significantly higher in specimens of nasopharyngeal swabs from COVID-19 patients. Protein expression of hBD-1 was also increased in the COVID-19 group. mRNA expression levels of interferon-ɣ (IFN-ɣ), tumor necrosis factor- ɑ (TNF-ɑ), and interleukin-6 (IL-6) measured in SARS-CoV-2-infected patients were significantly higher than those observed in the controls, which could also be confirmed in the protein levels of IFN-ɣ and IL-6. A significant correlation between mRNA and protein levels could be observed only for IL-6. Univariable analysis revealed that low IFN-ɣ mRNA levels were associated with severe/fatal outcomes. The occurrence of COVID-19 pneumonia was significantly associated with lower expression levels of IL-6 mRNA, IFN-ɣ mRNA, and TNF-ɑ mRNA. Concerning the severe/fatal outcomes, the multivariable logistic regression model revealed that none of the aforementioned parameters remained significant in the model. However, the logistic regression model revealed that higher TNF-ɑ mRNA expression was a significant independent predictor of absence of pneumonia [odds ratio: 0.35 (95% CI 0.14 to 0.88, p = 0.024)]. In conclusion, nasopharyngeal expression of AMPs (hBD-1, LL-37, and trappin-2) and cytokines (IL-6, IFN-ɣ, and TNF-ɑ) is upregulated in response to early SARS-CoV-2 infection, indicating that these AMPs and cytokines play a role in the local host defense against the virus. Upregulated nasopharyngeal TNF-ɑ mRNA expression during the early phase of SARS-CoV-2 infection was a significant independent predictor of the absence of COVID-19 pneumonia. Hence, high TNF-ɑ mRNA expression in the nasopharynx appears to be a protective factor for lung complications in COVID-19 patients.
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(This article belongs to the Special Issue Coronaviruses Pathogenesis, Immunity, and Antivirals)
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Knowledge and Awareness of Risk Factors for HIV Infection and about HIV Testing among Medical Students in Warsaw
by
Justyna Kowalska, Martyna Cholewik, Carlo Bieńkowski, Aleksandra Maciejczyk, Dominik Bursa and Agata Skrzat-Klapaczyńska
Viruses 2024, 16(9), 1470; https://doi.org/10.3390/v16091470 - 15 Sep 2024
Abstract
Background: The number of late diagnoses of HIV remains very high in Poland, leading to a high proportion of patients developing and dying of HIV-related diseases. The main reason for this is the very low utilization of HIV testing. Our analyses aimed to
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Background: The number of late diagnoses of HIV remains very high in Poland, leading to a high proportion of patients developing and dying of HIV-related diseases. The main reason for this is the very low utilization of HIV testing. Our analyses aimed to investigate knowledge about the indications for HIV testing among medical university students, as well as identify their own HIV testing experiences. Material and methods: A cross-sectional survey study was designed to collect information on the students’ demographics and their experiences of HIV testing, as well as their knowledge of virus transmission and the indications for testing. Data were collected as part of the HIV_week@WUM project conducted at the Medical University of Warsaw in parallel with the 18th European AIDS Conference, which took place in Warsaw between 18 and 21 October 2023. Results: In total, 545 questionnaires were collected. The median age of the study participants was 20 (interquartile range (IQR): 19–22 years). The majority of respondents were as follows: women (67.5%), born in Poland (97.8%), and were attending the medical faculty (56.7%). Only 114 (21.43%) participants had ever been tested for HIV. For all modes of HIV transmission, most of the respondents overestimated the risk of acquiring HIV, but, at the same time, they had never been tested for HIV. Conclusions: Only one in five health sciences students has ever had a test for HIV, which is less than estimates for the general population of Warsaw. There is an ongoing need to popularize testing among future health care providers in order to address both the indications for testing for individuals and the better use of HIV testing in clinical practice.
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(This article belongs to the Special Issue Cascade of Care for HIV and Hepatitis)
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Occurrence and Distribution of Major Cassava Pests and Diseases in Cultivated Cassava Varieties in Western Kenya
by
Everlyne N. Wosula, Rudolph R. Shirima, Massoud Amour, Vincent W. Woyengo, Bonface M. Otunga and James P. Legg
Viruses 2024, 16(9), 1469; https://doi.org/10.3390/v16091469 - 15 Sep 2024
Abstract
Cassava is an important food crop in western Kenya, yet its production is challenged by pests and diseases that require routine monitoring to guide development and deployment of control strategies. Field surveys were conducted in 2022 and 2023 to determine the prevalence, incidence
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Cassava is an important food crop in western Kenya, yet its production is challenged by pests and diseases that require routine monitoring to guide development and deployment of control strategies. Field surveys were conducted in 2022 and 2023 to determine the prevalence, incidence and severity of cassava mosaic disease (CMD) and cassava brown streak disease (CBSD), whitefly numbers and incidence of cassava green mite (CGM) in six counties of western Kenya. Details of the encountered cassava varieties were carefully recorded to determine the adoption of improved varieties. A total of 29 varieties were recorded, out of which 13 were improved, although the improved varieties were predominant in 60% of fields and the most widely grown variety was MM96/4271. The CMD incidence was higher in 2022 (26.4%) compared to 2023 (10.1%), although the proportion of CMD attributable to whitefly infection was greater (50.6%) in 2023 than in 2022 (18.0%). The CBSD incidence in 2022 was 6.4%, while in 2023 it was 4.1%. The CMD incidence was significantly lower (5.9%) for the improved varieties than it was for the local varieties (35.9%), although the CBSD incidence did not differ significantly between the improved (2.3%) and local varieties (9.7%). Cassava brown streak virus (CBSV) and Ugandan cassava brown streak virus (UCBSV) were both detected. Most infections were single CBSV infections (82.9%), followed by single UCBSV (34.3%) and coinfection with both viruses (16.7%). Whiteflies were more abundant in 2023, in which 28% of the fields had super-abundant populations of >100/plant, compared to 5% in 2022. KASP SNP genotyping designated 92.8% of the specimens as SSA-ECA for 2022, while it was 94.4% for 2023. The cassava green mite incidence was 65.4% in 2022 compared to 79.9% in 2023. This study demonstrates that cassava viruses, whiteflies and cassava green mites continue to be important constraints to cassava production in western Kenya, although the widespread cultivation of improved varieties is reducing the impact of cassava viruses. The more widespread application of high-quality seed delivery mechanisms could further enhance the management of these pests/diseases, coupled with wider application of IPM measures for whiteflies and mites.
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(This article belongs to the Special Issue Molecular Virus-Insect Interactions)
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Open AccessCommunication
Immunity Debt Regarding the Aspect of Influenza in the Post-COVID-19 Era in Taiwan
by
Edward Wu, Victoria Wu, Kang-Hsi Wu, Kun-Chan Wu and Jing-Yang Huang
Viruses 2024, 16(9), 1468; https://doi.org/10.3390/v16091468 - 15 Sep 2024
Abstract
Immunity debt for various viral infections was reported globally in the post-COVID-19 era, but the data about influenza are lacking. This study collected data from Taiwan’s CDC Open Data Portal. We analyzed the weekly number of influenza hospitalizations from January 2017 to May
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Immunity debt for various viral infections was reported globally in the post-COVID-19 era, but the data about influenza are lacking. This study collected data from Taiwan’s CDC Open Data Portal. We analyzed the weekly number of influenza hospitalizations from January 2017 to May 2024. We divided the study period into four phases: the pre-COVID-19 without influenza epidemics, pre-COVID-19 with an influenza epidemic, COVID-19 pandemic lockdown control, and COVID-19 pandemic unlock periods. The Wilcoxon rank-sum test and interrupted time series analysis were used. The median case numbers of the four time periods were 174 (IQR = 98), 431 (IQR = 160), 8, and 155 (IQR = 175), respectively. Under the COVID-19 pandemic lockdown control, the weekly influenza hospitalization case number decreased by 90.2% (p < 0.001). The non-pharmaceutical intervention (NPI) policies during the COVID-19 pandemic helped Taiwan reduce influenza hospitalizations significantly. Till now, a comparison of the prevalence of influenza pre-COVID-19 and post-COVID-19 has yet to be reported. In our study, with the pandemic unlocking, it increased by 20-fold (p < 0.001), but the case number was still significantly lower than that pre-COVID-19. Amongst other factors, this may be associated with continuing self-induced NPIs in Taiwan.
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(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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