Targeting Epigenetics to Cure HIV-1: Lessons From (and for) Cancer Treatment

Front Cell Infect Microbiol. 2021 May 7:11:668637. doi: 10.3389/fcimb.2021.668637. eCollection 2021.

Abstract

The Human Immunodeficiency Virus type 1 (HIV-1) integrates in the host genome as a provirus resulting in a long-lived reservoir of infected CD4 cells. As a provirus, HIV-1 has several aspects in common with an oncogene. Both the HIV-1 provirus and oncogenes only cause disease when expressed. A successful cure of both cancer and HIV-1 includes elimination of all cells with potential to regenerate the disease. For over two decades, epigenetic drugs developed against cancer have been used in the HIV-1 field to modulate the state of the proviral chromatin. Cells with an intact HIV-1 provirus exist in three states of infection: productive, inducible latent, and non-inducible latent. Here focus is on HIV-1, transcription control and chromatin structure; how the inducible proviruses are maintained in a chromatin structure that allows reactivation of transcription; and how transcription switches between different stages to allow for an abundance of different transcripts from a single promoter. Recently it was shown that a functional cure of HIV can be achieved by encapsulating all intact HIV-1 proviruses in heterochromatin, giving hope that epigenetic interventions may be used to end the HIV-1 epidemic.

Keywords: HIV cure; cancer; chromatin; epigenetics; transcription.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • CD4-Positive T-Lymphocytes
  • Epigenesis, Genetic
  • HIV Infections*
  • HIV-1*
  • Humans
  • Neoplasms*
  • Proviruses