Evolution of HIV-1 envelope towards reduced neutralization sensitivity, as demonstrated by contemporary HIV-1 subtype B from the United States

Lindsay Wieczorek, Eric Sanders-Buell, Michelle Zemil, Eric Lewitus, Erin Kavusak, Jonah Heller, Sebastian Molnar, Mekhala Rao, Gabriel Smith, Meera Bose, Amy Nguyen, Adwitiya Dhungana, Katherine Okada, Kelly Parisi, Daniel Silas, Bonnie Slike, Anuradha Ganesan, Jason Okulicz, Tahaniyat Lalani, Brian K AganTrevor A Crowell, Janice Darden, Morgane Rolland, Sandhya Vasan, Julie Ake, Shelly J Krebs, Sheila Peel, Sodsai Tovanabutra, Victoria R Polonis

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)e1011780
JournalPLoS Pathogens
Issue number12
StatePublished - Dec 2023


  • Humans
  • United States/epidemiology
  • HIV Infections
  • HIV Antibodies
  • Neutralization Tests
  • HIV-1/genetics
  • env Gene Products, Human Immunodeficiency Virus/genetics
  • Antibodies, Neutralizing
  • HIV Seropositivity
  • Pandemics


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