Infant transmitted/founder HIV-1 viruses from peripartum transmission are neutralization resistant to paired maternal plasma.
Despite extensive genetic diversity of HIV-1 in chronic infection, a single or few maternal virus variants become the founders of an infant's infection. These transmitted/founder (T/F) variants are of particular interest, as a maternal or infant HIV vaccine should raise envelope (Env) specific...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2018-04-01
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| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC5908066?pdf=render |
| _version_ | 1818502268694036480 |
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| author | Amit Kumar Claire E P Smith Elena E Giorgi Joshua Eudailey David R Martinez Karina Yusim Ayooluwa O Douglas Lisa Stamper Erin McGuire Celia C LaBranche David C Montefiori Genevieve G Fouda Feng Gao Sallie R Permar |
| author_facet | Amit Kumar Claire E P Smith Elena E Giorgi Joshua Eudailey David R Martinez Karina Yusim Ayooluwa O Douglas Lisa Stamper Erin McGuire Celia C LaBranche David C Montefiori Genevieve G Fouda Feng Gao Sallie R Permar |
| author_sort | Amit Kumar |
| collection | DOAJ |
| description | Despite extensive genetic diversity of HIV-1 in chronic infection, a single or few maternal virus variants become the founders of an infant's infection. These transmitted/founder (T/F) variants are of particular interest, as a maternal or infant HIV vaccine should raise envelope (Env) specific IgG responses capable of blocking this group of viruses. However, the maternal or infant factors that contribute to selection of infant T/F viruses are not well understood. In this study, we amplified HIV-1 env genes by single genome amplification from 16 mother-infant transmitting pairs from the U.S. pre-antiretroviral era Women Infant Transmission Study (WITS). Infant T/F and representative maternal non-transmitted Env variants from plasma were identified and used to generate pseudoviruses for paired maternal plasma neutralization sensitivity analysis. Eighteen out of 21 (85%) infant T/F Env pseudoviruses were neutralization resistant to paired maternal plasma. Yet, all infant T/F viruses were neutralization sensitive to a panel of HIV-1 broadly neutralizing antibodies and variably sensitive to heterologous plasma neutralizing antibodies. Also, these infant T/F pseudoviruses were overall more neutralization resistant to paired maternal plasma in comparison to pseudoviruses from maternal non-transmitted variants (p = 0.012). Altogether, our findings suggest that autologous neutralization of circulating viruses by maternal plasma antibodies select for neutralization-resistant viruses that initiate peripartum transmission, raising the speculation that enhancement of this response at the end of pregnancy could further reduce infant HIV-1 infection risk. |
| first_indexed | 2024-12-10T21:07:59Z |
| format | Article |
| id | doaj.art-1e3c487738a1442f80d4b880441b3f66 |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-10T21:07:59Z |
| publishDate | 2018-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-1e3c487738a1442f80d4b880441b3f662022-12-22T01:33:34ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742018-04-01144e100694410.1371/journal.ppat.1006944Infant transmitted/founder HIV-1 viruses from peripartum transmission are neutralization resistant to paired maternal plasma.Amit KumarClaire E P SmithElena E GiorgiJoshua EudaileyDavid R MartinezKarina YusimAyooluwa O DouglasLisa StamperErin McGuireCelia C LaBrancheDavid C MontefioriGenevieve G FoudaFeng GaoSallie R PermarDespite extensive genetic diversity of HIV-1 in chronic infection, a single or few maternal virus variants become the founders of an infant's infection. These transmitted/founder (T/F) variants are of particular interest, as a maternal or infant HIV vaccine should raise envelope (Env) specific IgG responses capable of blocking this group of viruses. However, the maternal or infant factors that contribute to selection of infant T/F viruses are not well understood. In this study, we amplified HIV-1 env genes by single genome amplification from 16 mother-infant transmitting pairs from the U.S. pre-antiretroviral era Women Infant Transmission Study (WITS). Infant T/F and representative maternal non-transmitted Env variants from plasma were identified and used to generate pseudoviruses for paired maternal plasma neutralization sensitivity analysis. Eighteen out of 21 (85%) infant T/F Env pseudoviruses were neutralization resistant to paired maternal plasma. Yet, all infant T/F viruses were neutralization sensitive to a panel of HIV-1 broadly neutralizing antibodies and variably sensitive to heterologous plasma neutralizing antibodies. Also, these infant T/F pseudoviruses were overall more neutralization resistant to paired maternal plasma in comparison to pseudoviruses from maternal non-transmitted variants (p = 0.012). Altogether, our findings suggest that autologous neutralization of circulating viruses by maternal plasma antibodies select for neutralization-resistant viruses that initiate peripartum transmission, raising the speculation that enhancement of this response at the end of pregnancy could further reduce infant HIV-1 infection risk.http://europepmc.org/articles/PMC5908066?pdf=render |
| spellingShingle | Amit Kumar Claire E P Smith Elena E Giorgi Joshua Eudailey David R Martinez Karina Yusim Ayooluwa O Douglas Lisa Stamper Erin McGuire Celia C LaBranche David C Montefiori Genevieve G Fouda Feng Gao Sallie R Permar Infant transmitted/founder HIV-1 viruses from peripartum transmission are neutralization resistant to paired maternal plasma. PLoS Pathogens |
| title | Infant transmitted/founder HIV-1 viruses from peripartum transmission are neutralization resistant to paired maternal plasma. |
| title_full | Infant transmitted/founder HIV-1 viruses from peripartum transmission are neutralization resistant to paired maternal plasma. |
| title_fullStr | Infant transmitted/founder HIV-1 viruses from peripartum transmission are neutralization resistant to paired maternal plasma. |
| title_full_unstemmed | Infant transmitted/founder HIV-1 viruses from peripartum transmission are neutralization resistant to paired maternal plasma. |
| title_short | Infant transmitted/founder HIV-1 viruses from peripartum transmission are neutralization resistant to paired maternal plasma. |
| title_sort | infant transmitted founder hiv 1 viruses from peripartum transmission are neutralization resistant to paired maternal plasma |
| url | http://europepmc.org/articles/PMC5908066?pdf=render |
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