PLoS Pathogens (Dec 2023)

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 Agan,
  • Trevor A Crowell,
  • Janice Darden,
  • Morgane Rolland,
  • Sandhya Vasan,
  • Julie Ake,
  • Shelly J Krebs,
  • Sheila Peel,
  • Sodsai Tovanabutra,
  • Victoria R Polonis

DOI
https://doi.org/10.1371/journal.ppat.1011780
Journal volume & issue
Vol. 19, no. 12
p. e1011780

Abstract

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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.