Clearance of HIV infection by selective elimination of host cells capable of producing HIV

Abstract

The RNA genome of the human immunodeficiency virus (HIV) is reverse-transcribed into DNA and integrated into the host genome, resulting in latent infections that are difficult to clear. Here we show an approach to eradicate HIV infections by selective elimination of host cells harboring replication-competent HIV (SECH), which includes viral reactivation, induction of cell death, inhibition of autophagy and the blocking of new infections. Viral reactivation triggers cell death specifically in HIV-1-infected T cells, which is promoted by agents that induce apoptosis and inhibit autophagy. SECH treatments can clear HIV-1 in >50% mice reconstituted with a human immune system, as demonstrated by the lack of viral rebound after withdrawal of treatments, and by adoptive transfer of treated lymphocytes into uninfected humanized mice. Moreover, SECH clears HIV-1 in blood samples from HIV-1-infected patients. Our results suggest a strategy to eradicate HIV infections by selectively eliminating host cells capable of producing HIV.

Document Details

Document Type
Pub Defense Publication
Publication Date
Aug 13, 2020
Source ID
10.1038/s41467-020-17753-w

Entities

People

  • Edward A Graviss
  • Jason T. Kimata
  • Jin Wang
  • Min Chen
  • Min Li
  • Roberto C. Arduino
  • Tonya Bauch
  • Wei Liu

Organizations

  • Cancer Prevention and Research Institute of Texas
  • National Institutes of Health
  • United States Department of Defense
  • United States Department of Health and Human Services

Tags

Fields of Study

  • Biology

Readers

  • Cellular and Molecular Pathways of Apoptosis.
  • Infectious Disease/Epidemiology
  • Oncology (Cancer Research).