HIV-1 Remission: Accelerating the Path to Permanent HIV-1 Silencing

Danielle E. Lyons, Priti Kumar, Nadia R. Roan, Patricia A. Defechereux, Cedric Feschotte, Ulrike C. Lange, Niren Murthy, Pauline Sameshima, Eric Verdin, Julie A. Ake, Matthew S. Parsons, Avindra Nath, Sara Gianella, Davey M. Smith, Esper G. Kallas, Thomas J. Villa, Richard Strange, Betty Mwesigwa, Robert L. Furler O’Brien, Douglas F. NixonLishomwa C. Ndhlovu*, Susana T. Valente*, Melanie Ott*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Despite remarkable progress, a cure for HIV-1 infection remains elusive. Rebound competent latent and transcriptionally active reservoir cells persevere despite antiretroviral therapy and rekindle infection due to inefficient proviral silencing. We propose a novel “block-lock-stop” approach, entailing long term durable silencing of viral expression towards an irreversible transcriptionally inactive latent provirus to achieve long term antiretroviral free control of the virus. A graded transformation of remnant HIV-1 in PLWH from persistent into silent to permanently defective proviruses is proposed, emulating and accelerating the natural path that human endogenous retroviruses (HERVs) take over millions of years. This hypothesis was based on research into delineating the mechanisms of HIV-1 latency, lessons from latency reversing agents and advances of Tat inhibitors, as well as expertise in the biology of HERVs. Insights from elite controllers and the availability of advanced genome engineering technologies for the direct excision of remnant virus set the stage for a rapid path to an HIV-1 cure.

Original languageEnglish
Article number2171
JournalViruses
Volume15
Issue number11
DOIs
StatePublished - Nov 2023
Externally publishedYes

Keywords

  • HERV
  • HIV-1 cure
  • latency
  • transcriptional silencing

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