{"title":"Conserved role of spike S2 domain N-glycosylation across betacoronaviruses.","authors":"Qi Yang, Anju Kelkar, Balaji Manicassamy, Sriram Neelamegham","doi":"10.1038/s44298-024-00085-7","DOIUrl":"https://doi.org/10.1038/s44298-024-00085-7","url":null,"abstract":"<p><p>Besides acting as an immunological shield, the N-glycans of SARS-CoV-2 are also critical for viral life cycle. As the S2 subunit of spike is highly conserved across betacoronaviruses, we determined the functional significance of the five 'stem N-glycans' located in S2 between N1098-N1194. Studies were performed with 31 Asn-to-Gln mutants, betacoronavirus virus-like particles and single-cycle viral replicons. Deletions of stem N-glycans enhanced S1 shedding from trimeric spike, reduced ACE2 binding and abolished syncytia formation. When three or more N-glycans were deleted, spike expression on cell surface and incorporation into virions was both reduced. Viral entry function was progressively lost upon deleting the N1098 glycan in combination with additional glycosite modifications. In addition to SARS-CoV-2, deleting stem N-glycans in SARS-CoV and MERS-CoV spike also prevented viral entry into target cells. These data suggest multiple functional roles for the stem N-glycans, and evolutionarily conserved properties for these complex carbohydrates across human betacoronaviruses.</p>","PeriodicalId":520240,"journal":{"name":"Npj viruses","volume":"3 1","pages":"4"},"PeriodicalIF":0.0,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144052647","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}
{"title":"Incompletely closed HIV-1<sub>CH040</sub> envelope glycoproteins resist broadly neutralizing antibodies while mediating efficient HIV-1 entry.","authors":"Durgadevi Parthasarathy, Stephanie Pickthorn, Shamim Ahmed, Dmitry Mazurov, Jeffy Jeffy, Rajni Kant Shukla, Amit Sharma, Alon Herschhorn","doi":"10.1038/s44298-024-00082-w","DOIUrl":"https://doi.org/10.1038/s44298-024-00082-w","url":null,"abstract":"<p><p>HIV-1 envelope glycoproteins (Envs) mediate viral entry and are sole target of neutralizing antibodies. Thus, HIV-1 Envs must maintain a delicate balance between evading neutralizing antibodies while still preserving viral compatibility to mediate entry into target cells. Here, we studied the viral entry effeciency, fitness, and replication of an incompletely closed, transmitted/founder HIV-1 Envs (CH040), which are highly resistant to most bnAbs. CH040 Envs mediated HIV-1 entry to target cells as efficient as other primary Envs, suggesting that antibody resistance and efficient viral entry can develop independently. Expression of CH040 Envs was comparable to other Envs and most CH040 variants that were rationally engineered to increase bnAb resistance showed no significant decrease in their ability to mediate HIV-1 entry. We detected robust in vitro spread of SHIV CH040 in pig-tailed macaque lymphocytes that was comparable to efficient spread of other SHIVs. Our study provides insights into the relationship between bnAb resistance and efficient HIV-1 entry.</p>","PeriodicalId":520240,"journal":{"name":"Npj viruses","volume":"3 1","pages":"3"},"PeriodicalIF":0.0,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11735869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144050626","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 : 2025-01-08DOI: 10.1038/s44298-024-00084-8
Monica Mirolo, Bianca Kühl, Melvin Daniel Roji, Ana Rubio-García, Valéria Andrade Lima, Christina Puff, Byron Martina, Andreas Beineke, Peter Wohlsein, Wolfgang Baumgärtner, Martin Ludlow, Albert Osterhaus
{"title":"Hepatovirus infections in juvenile seals from the North Sea.","authors":"Monica Mirolo, Bianca Kühl, Melvin Daniel Roji, Ana Rubio-García, Valéria Andrade Lima, Christina Puff, Byron Martina, Andreas Beineke, Peter Wohlsein, Wolfgang Baumgärtner, Martin Ludlow, Albert Osterhaus","doi":"10.1038/s44298-024-00084-8","DOIUrl":"https://doi.org/10.1038/s44298-024-00084-8","url":null,"abstract":"<p><p>The discovery of several novel hepatovirus species in marine and terrestrial mammals has expanded the recognised members of the genus Hepatovirus and has provided better understanding on the evolutionary origins of human hepatovirus A (HAV). Using high throughput sequencing we detected a seal hepatovirus (SealHAV_NL/PV/21), in liver tissue of a deceased harbor seal (Phoca vitulina) originating from the Dutch North Sea coast. RT-PCR screening of liver samples of 88 harbor seals and 12 grey seals (Halichoerus grypus) from the same region identified seal hepatovirus in nine juvenile harbor seals in which minor sequence variation was observed in the VP1 gene. Whole-genome sequence analysis showed that SealHAV_NL/PV/21 displayed 95.6% nucleotide indentity to New England seal hepatovirus but had a 5'-UTR which contained additional 51 bp. Phylogenetic analysis showed that seal hepatoviruses clustered in a monophyletic group separate from other hepatovirus species that have been identified in terrestrial mammals. Assessment of seal hepatovirus RNA loads in organs of all infected animals showed that the liver had the highest number of RNA copies with up to 10<sup>7</sup> RNA copies per mg of tissue. Seal hepatovirus RNA was readily detected by in situ hybridization in hepatocytes in the liver but was not associated with pathological lesions. Serological screening of 90 contemporary seal sera using a HAV-based ELISA showed the presence of hepatovirus antibodies in 14 harbor seals and one juvenile grey seal. These findings collectively show that seal hepatovirus is enzootic among seals of the North Sea, causing quiescent infections in young animals.</p>","PeriodicalId":520240,"journal":{"name":"Npj viruses","volume":"3 1","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11721073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998399","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 : 2025-01-08DOI: 10.1038/s44298-024-00086-6
Sophie M Kolbe, Kate Guilfoyle, Wencke Reineking, Geert van Amerongen, Guido van der Net, Sandra Lockow, Wolfgang Baumgärtner, Martin Ludlow, Albert D M E Osterhaus
{"title":"Syrian hamsters (Mesocricetus auratus) as an upper respiratory tract model for respiratory syncytial virus infection.","authors":"Sophie M Kolbe, Kate Guilfoyle, Wencke Reineking, Geert van Amerongen, Guido van der Net, Sandra Lockow, Wolfgang Baumgärtner, Martin Ludlow, Albert D M E Osterhaus","doi":"10.1038/s44298-024-00086-6","DOIUrl":"https://doi.org/10.1038/s44298-024-00086-6","url":null,"abstract":"<p><p>Respiratory syncytial virus (RSV) is one of the leading causes of respiratory tract infection in children, immunocompromised individuals and older adults. Vaccines have recently been approved for use in adults and although further efforts to develop suitable interventions for children are ongoing, there are limited animal models for RSV infection. For preclinical efficacy testing of prophylactic and therapeutic treatments cotton rat and ferret models can be used. However, these can be expensive, difficult to source and house, and often have limitations such as insufficient virus replication in the respiratory tract and/or lack of horizontal transmission. In this study, Syrian hamsters (Mesocricetus auratus), which are relatively cheap, easy to source and house, were inoculated intranasally with a recombinant RSV-A-0594 strain expressing EGFP and using virological and pathological analyses. Viral replication was assessed and compared to viral replication in the ferret model. Although there was limited virus infection of the lower respiratory tract of Syrian hamsters, we show that a contemporary recombinant RSV-A strain replicates efficiently in the upper respiratory tract of Syrian hamsters (titers up to 4.5 Log10 TCID50/g and 12 Log10 RNA copies/g). These titers are comparable to those found in the ferret upper respiratory tract tissues post-infection with the same virus strain (up to 6.0 Log10 TCID50/g and 12 Log 10 RNA copies/g). Fluorescent regions indicating virus infection were macroscopically visible under UV-light in the nasal turbinates and histological assessment showed mucosal inflammation with necrotic cells in this tissue. In summary, Syrian hamsters generally displayed less severe systemic and pulmonary changes than ferrets, but do appear to be a promising model for upper respiratory tract infection with RSV.</p>","PeriodicalId":520240,"journal":{"name":"Npj viruses","volume":"3 1","pages":"2"},"PeriodicalIF":0.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11721388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144061976","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}
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