Npj virusesPub Date : 2025-04-04DOI: 10.1038/s44298-025-00106-z
Edwin O Ogola, Amitava Roy, Kurt Wollenberg, Missiani Ochwoto, Marshall E Bloom
{"title":"Strange relatives: the enigmatic arbo-jingmenviruses and orthoflaviviruses.","authors":"Edwin O Ogola, Amitava Roy, Kurt Wollenberg, Missiani Ochwoto, Marshall E Bloom","doi":"10.1038/s44298-025-00106-z","DOIUrl":"https://doi.org/10.1038/s44298-025-00106-z","url":null,"abstract":"<p><p>Arthropod - and vertebrate-associated jingmenviruses (arbo-JMV) have segmented positive-strand RNA genomes and are provisional members of the genus Orthoflavivirus (family Flaviviridae). Current investigations have described arbo-JMV infection in vertebrate hosts in proximity to humans. This raises concerns about the virus host range and public health implications. This review explores the genomic and evolutionary relationship between arbo-JMV and orthoflaviviruses and evaluates the potential of arbo-JMV to pose a public health threat.</p>","PeriodicalId":520240,"journal":{"name":"Npj viruses","volume":"3 1","pages":"24"},"PeriodicalIF":0.0,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11971299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Npj virusesPub Date : 2025-04-04DOI: 10.1038/s44298-025-00108-x
Karen Martiny, Yuan Liang, Pia Ryt-Hansen, Lars E Larsen, Jens P Christensen, Charlotte K Hjulsager
{"title":"Lentogenic avian paramyxovirus 1 of both class I and class II are circulating in danish wild and commercial waterfowl.","authors":"Karen Martiny, Yuan Liang, Pia Ryt-Hansen, Lars E Larsen, Jens P Christensen, Charlotte K Hjulsager","doi":"10.1038/s44298-025-00108-x","DOIUrl":"https://doi.org/10.1038/s44298-025-00108-x","url":null,"abstract":"<p><p>Newcastle disease, a notifiable avian disease, is caused by virulent avian paramyxovirus 1 (APMV-1). In this study, we screened samples collected through the active and passive surveillance for avian influenza virus in Denmark between 2014 and 2022 for APMV-1, detecting 32 APMV-1 in wild and commercial waterfowl. Phylogenetic analysis identified them as class I genotype 1.2 and class II genotype I.2 viruses, all with monobasic fusion (F) cleavage sites (<sup>112</sup>ERQERL<sup>117</sup> and <sup>112</sup>GKQGRL<sup>117</sup>), characterizing them as lentogenic. Nucleotide and amino acid similarities ranged from 95 to 99.8% and 98.2 to 100% for class I viruses and 95.6-99.8% and 98.7-100% for class II viruses. Genetic comparisons of F genes showed divergence from vaccine strains, ruling out vaccine spillover. Selection analysis revealed neutral and negative selection pressures, suggesting limited adaptive evolution. These findings indicate that lentogenic APMV-1 circulated in Denmark from 2014 to 2022 without strong selection pressures driving significant genetic changes.</p>","PeriodicalId":520240,"journal":{"name":"Npj viruses","volume":"3 1","pages":"26"},"PeriodicalIF":0.0,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11971311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Npj virusesPub Date : 2025-04-01DOI: 10.1038/s44298-025-00104-1
Daniel Lauster, Rainer Haag, Matthias Ballauff, Andreas Herrmann
{"title":"Balancing stability and function: impact of the surface charge of SARS-CoV-2 Omicron spike protein.","authors":"Daniel Lauster, Rainer Haag, Matthias Ballauff, Andreas Herrmann","doi":"10.1038/s44298-025-00104-1","DOIUrl":"https://doi.org/10.1038/s44298-025-00104-1","url":null,"abstract":"<p><p>The ectodomain of the Omicron SARS-CoV-2 spike has an increased positive surface charge, favoring binding to the host cell surface, but may affect the stability of the ectodomain. Thermal stability studies identified two transitions associated with the flexibility of the receptor binding domain and the unfolding of the whole ectodomain, respectively. Despite destabilizing effects of some mutations, compensatory mutations maintain ECD stability and functional advantages thus supporting viral fitness.</p>","PeriodicalId":520240,"journal":{"name":"Npj viruses","volume":"3 1","pages":"23"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11962157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Npj virusesPub Date : 2025-03-28DOI: 10.1038/s44298-025-00090-4
Jens Kleinehr, Chiara Robin Bojarzyn, Michael Schöfbänker, Katharina Daniel, Stephan Ludwig, Eike R Hrincius
{"title":"Metabolic interference impairs influenza A virus replication by dampening vRNA synthesis.","authors":"Jens Kleinehr, Chiara Robin Bojarzyn, Michael Schöfbänker, Katharina Daniel, Stephan Ludwig, Eike R Hrincius","doi":"10.1038/s44298-025-00090-4","DOIUrl":"https://doi.org/10.1038/s44298-025-00090-4","url":null,"abstract":"<p><p>For replication, viruses exploit the host cell metabolism for biosynthesis of viral components. Recently, we could show that inhibition of glycolysis interfered with IAV replication by impairing the regulation of the viral polymerase as a transcriptase or replicase. Here, we investigated how IAV replication and polymerase regulation is influenced by other metabolic pathways which are directly or indirectly linked to glycolysis. Therefore, we inhibited glutaminolysis, fatty acid synthesis (FAS), oxidative phosphorylation (OXPHOS), and the pentose phosphate pathway (PPP). Inhibition of these metabolic pathways led to a significant reduction of viral titers. Furthermore, the inhibition of glutaminolysis, FAS and OXPHOS unbalanced the cellular glycolysis and respiration network leading to a prolonged phase of viral transcription while replication was strongly decreased. Our data indicate that affecting the cellular glycolysis and respiration balance impairs the dynamic regulation of the viral polymerase, resulting in reduced synthesis of viral genomic RNA and viral particles.</p>","PeriodicalId":520240,"journal":{"name":"Npj viruses","volume":"3 1","pages":"22"},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11953304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144057562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Npj virusesPub Date : 2025-03-28DOI: 10.1038/s44298-025-00105-0
Christopher Mauer, Sean Paz, Massimo Caputi
{"title":"Backsplicing of the HIV-1 transcript generates multiple circRNAs to promote viral replication.","authors":"Christopher Mauer, Sean Paz, Massimo Caputi","doi":"10.1038/s44298-025-00105-0","DOIUrl":"https://doi.org/10.1038/s44298-025-00105-0","url":null,"abstract":"<p><p>Circular RNAs (circRNAs) are a family of non-coding RNAs that originate from a non-canonical splicing event (backsplicing) that forms covalently closed continuous loops. An analysis of the human immunodeficiency type 1 virus (HIV-1) complex splicing pattern indicated that the virus had the potential to generate at least 15 distinct circRNAs. The predicted HIV circRNAs were amplified utilizing divergent PCR primers and confirmed by RNase R digestion and sequencing. A predictive circRNA-miRNA interaction modeling approach and a series of validation assays determined that two cellular miRNAs, miR-6727-3p and miR-4722-3p, functionally interact with a sequence present in 8 of the HIV circRNAs. Expression of miR-6727-3p and miR-4722-3p restricted HIV-1 replication while a circRNA containing the sequence recognized by miR-6727-3p and miR-4722-3p increased the production of infective virions. Additionally, miR-6727-3p and miR-4722-3p expression was upregulated following HIV-1 infection of primary CD4+ T cells. Overall, the data presented shows that HIV-1 generates circRNAs which promote viral replication by sequestering and inhibiting the functions of miR-6727-3p and miR-4722-3p.</p>","PeriodicalId":520240,"journal":{"name":"Npj viruses","volume":"3 1","pages":"21"},"PeriodicalIF":0.0,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11953466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Npj virusesPub Date : 2025-03-13DOI: 10.1038/s44298-025-00102-3
Mohammad Enamul Hoque Kayesh, Michinori Kohara, Kyoko Tsukiyama-Kohara
{"title":"Toll-like receptor response to Zika virus infection: progress toward infection control.","authors":"Mohammad Enamul Hoque Kayesh, Michinori Kohara, Kyoko Tsukiyama-Kohara","doi":"10.1038/s44298-025-00102-3","DOIUrl":"https://doi.org/10.1038/s44298-025-00102-3","url":null,"abstract":"<p><p>Infection with the Zika virus (ZIKV) poses a threat to human health. An improved understanding of the host Toll-like receptor response, disease onset, and viral clearance in vivo and in vitro may lead to the development of therapeutic or prophylactic interventions against viral infections. Currently, no clinically approved ZIKV vaccine is available, highlighting the need for its development. In this study, we discuss the progress in the Zika vaccine, including advances in the use of Toll-like receptor agonists as vaccine adjuvants to enhance vaccine efficacy.</p>","PeriodicalId":520240,"journal":{"name":"Npj viruses","volume":"3 1","pages":"20"},"PeriodicalIF":0.0,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Npj virusesPub Date : 2025-03-13DOI: 10.1038/s44298-025-00101-4
Peter J Halfmann, Jeong Soo Lee, Nikki McArthur, Ojas Gupta, Yoshihiro Kawaoka, Ravi S Kane
{"title":"Potent bivalent nanobody constructs that protect against the SARS-CoV-2 XBB variant.","authors":"Peter J Halfmann, Jeong Soo Lee, Nikki McArthur, Ojas Gupta, Yoshihiro Kawaoka, Ravi S Kane","doi":"10.1038/s44298-025-00101-4","DOIUrl":"https://doi.org/10.1038/s44298-025-00101-4","url":null,"abstract":"<p><p>Most antibody-based therapeutics approved for SARS-CoV-2 treatment have shown greatly reduced neutralization activity against emerging Omicron variants. To target recent Omicron variants, we developed XBB-specific antibody-like therapeutics by screening a yeast surface-displayed single-domain antibody library against the receptor binding domain of the XBB spike protein. Three lead nanobodies, XNb 4.13, XNb 4.14, and XNb 4.15, were selected based on their binding affinity to the XBB spike protein and were fused to a mouse Fc domain. While all three constructs showed sub-nanomolar binding affinities to the XBB S protein, XNb 4.13-Fc and XNb 4.14-Fc also neutralized XBB in vitro. Intraperitoneal injection of XNb 4.13-Fc and XNb 4.14-Fc and intranasal delivery of XNb 4.13-Fc protected transgenic mice from a challenge with XBB virus with a significant reduction in viral lung titers post-infection. These antibody-like constructs identified using yeast surface display have potential as therapeutics that can protect against SARS-CoV-2 XBB variants.</p>","PeriodicalId":520240,"journal":{"name":"Npj viruses","volume":"3 1","pages":"19"},"PeriodicalIF":0.0,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Npj virusesPub Date : 2025-02-27DOI: 10.1038/s44298-025-00100-5
Deepashri Rao, Matthew Lewis, Kimberly Meade-White, Carl Shaia, Atsushi Okumura, Martin T Ferris, Alexandra Schäfer, Ralph Baric, Heinz Feldmann, David W Hawman
{"title":"Host genetic diversity contributes to disease outcome in Crimean-Congo hemorrhagic fever virus infection.","authors":"Deepashri Rao, Matthew Lewis, Kimberly Meade-White, Carl Shaia, Atsushi Okumura, Martin T Ferris, Alexandra Schäfer, Ralph Baric, Heinz Feldmann, David W Hawman","doi":"10.1038/s44298-025-00100-5","DOIUrl":"https://doi.org/10.1038/s44298-025-00100-5","url":null,"abstract":"<p><p>The Crimean-Congo hemorrhagic fever virus (CCHFV) causes Crimean-Congo hemorrhagic fever (CCHF), a widely distributed disease with significant morbidity and mortality. The virus has high genetic diversity correlated with geographic distribution but limited temporal evolution within regions. Despite this, cases of CCHF within a region present as a spectrum of disease from often unrecognized asymptomatic infections to severe, fatal viral hemorrhagic fever, suggesting host factors may play a role in disease outcome. We investigated the effect of host genetic diversity on the outcome of CCHFV infection in the genetically diverse Collaborative cross (CC)-mouse model. Infected mice recapitulated the full spectrum of disease recognized in humans, and similar to human disease, virus replication, tissue pathology, and inflammatory responses were associated with disease severity. Our study demonstrates that host genetics contribute to disease outcome in CCHF infection and establishes the CC mouse resource as a model to understand how host genetic diversity contributes to CCHF outcome.</p>","PeriodicalId":520240,"journal":{"name":"Npj viruses","volume":"3 1","pages":"16"},"PeriodicalIF":0.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11868557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Npj virusesPub Date : 2025-02-24DOI: 10.1038/s44298-025-00092-2
Andra Banete, Bryan D Griffin, Juan C Corredor, Emily Chien, Lily Yip, Tarini N A Gunawardena, Kuganya Nirmalarajah, Jady Liang, Yaejin Lee, Alexander Leacy, Sara Pagliarani, Richard de Borja, Winfield Yim, Hunsang Lee, Yu Onodera, Patryk Aftanas, Patrick Budylowski, Sang Kyun Ahn, Yanlong Pei, Hong Ouyang, Laura Kent, Xinliu Angel Li, Mario A Ostrowski, Robert A Kozak, Sarah K Wootton, Natasha Christie-Holmes, Scott D Gray-Owen, Mikko Taipale, Jared T Simpson, Finlay Maguire, Allison J McGeer, Haibo Zhang, Leonardo Susta, Theo J Moraes, Samira Mubareka
{"title":"Pathogenesis and transmission of SARS-CoV-2 D614G, Alpha, Gamma, Delta, and Omicron variants in golden hamsters.","authors":"Andra Banete, Bryan D Griffin, Juan C Corredor, Emily Chien, Lily Yip, Tarini N A Gunawardena, Kuganya Nirmalarajah, Jady Liang, Yaejin Lee, Alexander Leacy, Sara Pagliarani, Richard de Borja, Winfield Yim, Hunsang Lee, Yu Onodera, Patryk Aftanas, Patrick Budylowski, Sang Kyun Ahn, Yanlong Pei, Hong Ouyang, Laura Kent, Xinliu Angel Li, Mario A Ostrowski, Robert A Kozak, Sarah K Wootton, Natasha Christie-Holmes, Scott D Gray-Owen, Mikko Taipale, Jared T Simpson, Finlay Maguire, Allison J McGeer, Haibo Zhang, Leonardo Susta, Theo J Moraes, Samira Mubareka","doi":"10.1038/s44298-025-00092-2","DOIUrl":"https://doi.org/10.1038/s44298-025-00092-2","url":null,"abstract":"<p><p>Since the emergence of SARS-CoV-2 in humans, novel variants have evolved to become dominant circulating lineages. These include D614G (B.1 lineage), Alpha (B.1.1.7), Gamma (P.1), Delta (B.1.617.2), and Omicron BA.1 (B.1.1.529) and BA.2 (B.1.1.529.2) viruses. Here, we compared the viral replication, pathogenesis, and transmissibility of these variants. Replication kinetics and innate immune response against the viruses were tested in ex vivo human nasal epithelial cells (HNEC) and induced pluripotent stem cell-derived lung organoids (IPSC-LOs), and the golden hamster model was employed to test pathogenicity and potential for transmission by the respiratory route. Delta, BA.1, and BA.2 viruses replicated more efficiently, and outcompeted D614G, Alpha, and Gamma viruses in an HNEC competition assay. BA.1 and BA.2 viruses, however, replicated poorly in IPSC-LOs compared to other variants. Moreover, BA.2 virus infection significantly increased secretion of IFN-λ1, IFN-λ2, IFN-λ3, IL-6, and IL-1RA in HNECs relative to D614G infection, but not in IPSC-LOs. The BA.1 and BA.2 viruses replicated less effectively in hamster lungs compared to the other variants; and while the Gamma virus reached titers comparable to D614G and Delta viruses, it caused greater lung pathology. Lastly, the Gamma and Delta variants transmitted more efficiently by the respiratory route compared to the other viruses, while BA.1 and BA.2 viruses transmitted less efficiently. These findings demonstrate the ongoing utility of experimental risk assessment as SARS-CoV-2 variants continue to evolve.</p>","PeriodicalId":520240,"journal":{"name":"Npj viruses","volume":"3 1","pages":"15"},"PeriodicalIF":0.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144061404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}