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

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 inves...

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Bibliographic Details
Published in:Clinical microbiology reviews 2019-12, Vol.33 (1)
Main Authors: Chandrasekar, Aswath P, Cummins, Nathan W, Badley, Andrew D
Format: Article
Language:English
Subjects:
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
Review
Viral Load
Virus Activation
Virus Latency
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Summary: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.
ISSN:0893-8512
1098-6618
1098-6618
DOI:10.1128/CMR.00107-19