Incompletely closed HIV-1CH040 envelope glycoproteins resist broadly neutralizing antibodies while mediating efficient HIV-1 entry
Abstract 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 t...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | npj Viruses |
| Online Access: | https://doi.org/10.1038/s44298-024-00082-w |
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| author | Durgadevi Parthasarathy Stephanie Pickthorn Shamim Ahmed Dmitry Mazurov Jeffy Jeffy Rajni Kant Shukla Amit Sharma Alon Herschhorn |
| author_facet | Durgadevi Parthasarathy Stephanie Pickthorn Shamim Ahmed Dmitry Mazurov Jeffy Jeffy Rajni Kant Shukla Amit Sharma Alon Herschhorn |
| author_sort | Durgadevi Parthasarathy |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-83dc478de8f44a1593006f3393135816 |
| institution | Kabale University |
| issn | 2948-1767 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Viruses |
| spelling | doaj-art-83dc478de8f44a1593006f33931358162025-01-19T12:12:59ZengNature Portfolionpj Viruses2948-17672025-01-013111310.1038/s44298-024-00082-wIncompletely closed HIV-1CH040 envelope glycoproteins resist broadly neutralizing antibodies while mediating efficient HIV-1 entryDurgadevi Parthasarathy0Stephanie Pickthorn1Shamim Ahmed2Dmitry Mazurov3Jeffy Jeffy4Rajni Kant Shukla5Amit Sharma6Alon Herschhorn7Division of Infectious Diseases and International Medicine, Department of Medicine, University of MinnesotaDivision of Infectious Diseases and International Medicine, Department of Medicine, University of MinnesotaDivision of Infectious Diseases and International Medicine, Department of Medicine, University of MinnesotaDivision of Infectious Diseases and International Medicine, Department of Medicine, University of MinnesotaDivision of Infectious Diseases and International Medicine, Department of Medicine, University of MinnesotaDepartment of Veterinary Biosciences, Department of Microbial Infection & Immunity, The Ohio State UniversityDepartment of Veterinary Biosciences, Department of Microbial Infection & Immunity, The Ohio State UniversityDivision of Infectious Diseases and International Medicine, Department of Medicine, University of MinnesotaAbstract 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.https://doi.org/10.1038/s44298-024-00082-w |
| spellingShingle | Durgadevi Parthasarathy Stephanie Pickthorn Shamim Ahmed Dmitry Mazurov Jeffy Jeffy Rajni Kant Shukla Amit Sharma Alon Herschhorn Incompletely closed HIV-1CH040 envelope glycoproteins resist broadly neutralizing antibodies while mediating efficient HIV-1 entry npj Viruses |
| title | Incompletely closed HIV-1CH040 envelope glycoproteins resist broadly neutralizing antibodies while mediating efficient HIV-1 entry |
| title_full | Incompletely closed HIV-1CH040 envelope glycoproteins resist broadly neutralizing antibodies while mediating efficient HIV-1 entry |
| title_fullStr | Incompletely closed HIV-1CH040 envelope glycoproteins resist broadly neutralizing antibodies while mediating efficient HIV-1 entry |
| title_full_unstemmed | Incompletely closed HIV-1CH040 envelope glycoproteins resist broadly neutralizing antibodies while mediating efficient HIV-1 entry |
| title_short | Incompletely closed HIV-1CH040 envelope glycoproteins resist broadly neutralizing antibodies while mediating efficient HIV-1 entry |
| title_sort | incompletely closed hiv 1ch040 envelope glycoproteins resist broadly neutralizing antibodies while mediating efficient hiv 1 entry |
| url | https://doi.org/10.1038/s44298-024-00082-w |
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