Deep latency: A new insight into a functional HIV cure

EBioMedicine. 2019 Jul:45:624-629. doi: 10.1016/j.ebiom.2019.06.020. Epub 2019 Jun 18.

Abstract

Latent HIV reservoir is the main obstacle that prevents a cure for HIV-1 (HIV). While antiretroviral therapy is effective in controlling viral replication, it cannot eliminate latent HIV reservoirs in patients. Several strategies have been proposed to combat HIV latency, including bone marrow transplantation to replace blood cells with CCR5-mutated stem cells, gene editing to disrupt the HIV genome, and "Shock and Kill" to reactivate latent HIV followed by an immune clearance. However, high risks and limitations to scale-up in clinics, off-target effects in human genomes or failure to reduce reservoir sizes in patients hampered our current efforts to achieve an HIV cure. This necessitates alternative strategies to control the latent HIV reservoirs. This review will discuss an emerging strategy aimed to deeply silence HIV reservoirs, the development of this concept, its potential and caveats for HIV remission/cure, and prospective directions for silencing the latent HIV, thereby preventing viruses from rebound.

Keywords: Deep latency; HIV latency; HIV reservoirs; Shock and kill; Transcription.

Publication types

  • Review

MeSH terms

  • CD4-Positive T-Lymphocytes / virology
  • Disease Reservoirs / virology*
  • HIV Infections / epidemiology
  • HIV Infections / genetics*
  • HIV Infections / transmission
  • HIV Infections / virology
  • HIV-1 / genetics*
  • HIV-1 / pathogenicity
  • Humans
  • Receptors, CCR5 / genetics
  • Virus Activation / genetics
  • Virus Latency / genetics*
  • Virus Replication / genetics

Substances

  • CCR5 protein, human
  • Receptors, CCR5