The Role of the BCL-2 Family of Proteins in HIV-1 Pathogenesis and Persistence

Clin Microbiol Rev. 2019 Oct 30;33(1):e00107-19. doi: 10.1128/CMR.00107-19. Print 2019 Dec 18.

Abstract

Advances in HIV-1 therapy have transformed the once fatal infection into a manageable, chronic condition, yet the search for a widely applicable approach to cure remains elusive. The ineffectiveness of antiretroviral therapy (ART) in reducing the size of the HIV-1 latent reservoir has prompted investigation into the mechanisms of HIV-1 latency and immune escape. One of the major regulators of apoptosis, the BCL-2 protein, alongside its homologous family members, is a major target of HIV-1-induced change. Recent studies have now demonstrated the association of this protein with cells that support proviral forms in the setting of latency and have helped identify BCL-2 as a novel and promising therapeutic target for HIV-1 therapy directed at possible cure. This review aims to systematically review the interactions of HIV-1 with BCL-2 and its homologs and to examine the possibility of using BCL-2 inhibitors in the study and elimination of the latent reservoir.

Keywords: BCL-2 family; antiapoptosis; apoptosis; human immunodeficiency virus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-HIV Agents / pharmacology
  • Anti-HIV Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active
  • Disease Susceptibility
  • HIV Infections / drug therapy
  • HIV Infections / metabolism*
  • HIV Infections / virology*
  • HIV-1 / drug effects
  • HIV-1 / physiology*
  • Host-Pathogen Interactions* / genetics
  • Humans
  • Multigene Family
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Viral Load
  • Virus Activation
  • Virus Latency*

Substances

  • Anti-HIV Agents
  • BCL2 protein, human
  • Proto-Oncogene Proteins c-bcl-2