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

• 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
• ISSN: 0893-8512; 1098-6618; 1098-6618
• DOI: 10.1128/CMR.00107-19

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.