Evolution of HIV-1 envelope towards reduced neutralization sensitivity, as demonstrated by contemporary HIV-1 subtype B from the United States
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Published:2023-12-06
Issue:12
Volume:19
Page:e1011780
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ISSN:1553-7374
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Container-title:PLOS Pathogens
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language:en
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Short-container-title:PLoS Pathog
Author:
Wieczorek LindsayORCID, Sanders-Buell Eric, Zemil Michelle, Lewitus Eric, Kavusak Erin, Heller Jonah, Molnar Sebastian, Rao Mekhala, Smith Gabriel, Bose Meera, Nguyen Amy, Dhungana Adwitiya, Okada Katherine, Parisi Kelly, Silas Daniel, Slike Bonnie, Ganesan Anuradha, Okulicz Jason, Lalani Tahaniyat, Agan Brian K., Crowell Trevor A., Darden Janice, Rolland Morgane, Vasan Sandhya, Ake Julie, Krebs Shelly J., Peel Sheila, Tovanabutra Sodsai, Polonis Victoria R.ORCID
Abstract
Subtype B HIV-1 has been the primary driver of the HIV-1 epidemic in the United States (U.S.) for over forty years and is also a prominent subtype in the Americas, Europe, Australia, the Middle East and North Africa. In this study, the neutralization profiles of contemporary subtype B Envs from the U.S. were assessed to characterize changes in neutralization sensitivities over time. We generated a panel of 30 contemporary pseudoviruses (PSVs) and demonstrated continued diversification of subtype B Env from the 1980s up to 2018. Neutralization sensitivities of the contemporary subtype B PSVs were characterized using 31 neutralizing antibodies (NAbs) and were compared with strains from earlier in the HIV-1 pandemic. A significant reduction in Env neutralization sensitivity was observed for 27 out of 31 NAbs for the contemporary as compared to earlier-decade subtype B PSVs. A decline in neutralization sensitivity was observed across all Env domains; the NAbs that were most potent early in the pandemic suffered the greatest decline in potency over time. A meta-analysis demonstrated this trend across multiple subtypes. As HIV-1 Env diversification continues, changes in Env antigenicity and neutralization sensitivity should continue to be evaluated to inform the development of improved vaccine and antibody products to prevent and treat HIV-1.
Funder
U.S. Department of Defense Division of Intramural Research, National Institute of Allergy and Infectious Diseases
Publisher
Public Library of Science (PLoS)
Subject
Virology,Genetics,Molecular Biology,Immunology,Microbiology,Parasitology
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