Infant transmitted/founder HIV-1 viruses from peripartum transmission are neutralization resistant to paired maternal plasma
Abstract
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 motherinfant 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 antibodiesmore »
- Authors:
-
[1];
[1];
[3];
[1];
[1]
- Duke Univ., Durham, NC (United States). Medical Center. Duke Human Vaccine Inst.
- Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
- Duke Univ., Durham, NC (United States). Medical Center. Dept. of Surgery
- Duke Univ., Durham, NC (United States). Medical Center. Dept. of Medicine; Jilin Univ., Changchun (China). National Engineering Lab. for AIDS Vaccine
- Publication Date:
- Research Org.:
- Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
- OSTI Identifier:
- 1627917
- Grant/Contract Number:
- AC52-06NA25396
- Resource Type:
- Accepted Manuscript
- Journal Name:
- PLoS Pathogens
- Additional Journal Information:
- Journal Volume: 14; Journal Issue: 4; Journal ID: ISSN 1553-7374
- Publisher:
- Public Library of Science
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; Microbiology; Parasitology; Virology
Citation Formats
Kumar, Amit, Smith, Claire E. P., Giorgi, Elena E., Eudailey, Joshua, Martinez, David R., Yusim, Karina, Douglas, Ayooluwa O., Stamper, Lisa, McGuire, Erin, LaBranche, Celia C., Montefiori, David C., Fouda, Genevieve G., Gao, Feng, and Permar, Sallie R. Infant transmitted/founder HIV-1 viruses from peripartum transmission are neutralization resistant to paired maternal plasma. United States: N. p., 2018.
Web. doi:10.1371/journal.ppat.1006944.
Kumar, Amit, Smith, Claire E. P., Giorgi, Elena E., Eudailey, Joshua, Martinez, David R., Yusim, Karina, Douglas, Ayooluwa O., Stamper, Lisa, McGuire, Erin, LaBranche, Celia C., Montefiori, David C., Fouda, Genevieve G., Gao, Feng, & Permar, Sallie R. Infant transmitted/founder HIV-1 viruses from peripartum transmission are neutralization resistant to paired maternal plasma. United States. https://doi.org/10.1371/journal.ppat.1006944
Kumar, Amit, Smith, Claire E. P., Giorgi, Elena E., Eudailey, Joshua, Martinez, David R., Yusim, Karina, Douglas, Ayooluwa O., Stamper, Lisa, McGuire, Erin, LaBranche, Celia C., Montefiori, David C., Fouda, Genevieve G., Gao, Feng, and Permar, Sallie R. Thu .
"Infant transmitted/founder HIV-1 viruses from peripartum transmission are neutralization resistant to paired maternal plasma". United States. https://doi.org/10.1371/journal.ppat.1006944. https://www.osti.gov/servlets/purl/1627917.
@article{osti_1627917,
title = {Infant transmitted/founder HIV-1 viruses from peripartum transmission are neutralization resistant to paired maternal plasma},
author = {Kumar, Amit and Smith, Claire E. P. and Giorgi, Elena E. and Eudailey, Joshua and Martinez, David R. and Yusim, Karina and Douglas, Ayooluwa O. and Stamper, Lisa and McGuire, Erin and LaBranche, Celia C. and Montefiori, David C. and Fouda, Genevieve G. and Gao, Feng and Permar, Sallie R.},
abstractNote = {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 motherinfant 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 HIV1 infection risk.},
doi = {10.1371/journal.ppat.1006944},
journal = {PLoS Pathogens},
number = 4,
volume = 14,
place = {United States},
year = {Thu Apr 19 00:00:00 EDT 2018},
month = {Thu Apr 19 00:00:00 EDT 2018}
}
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