Title: Insights into the HIV latency and the role of cytokines
Author(s): Joseph Hokello, Adhikarimayum Lakhikumar Sharma, Manjari Dimri and Mudit Tyagi
Year 2019
Publisher: Pathogens 2019, 8, x;
File: PDF
Keywords: HIV-1 latency eradication transforming growth factor-beta (TGF-β) resting memory CD4+ T-cells

Human immunodeficiency virus-1 (HIV-1) has the ability to infect latently at the level of individual CD4+ cells. Latent HIV-1 proviruses are transcriptionally silent and immunologically inert, but still capable of reactivating productive lytic infection following cellular activation. These latent viruses are the main obstacle in the eradication of HIV-1 because current HIV-1 treatment regimens are ineffective against them. Normal immunological response against an antigen activates CD4+ naïve T cells. The activated CD4+ naïve T cells undergo cell cycle, resulting in further transformation and profound proliferation to form effector CD4+T-cells. Notably, in HIV-1 infected individuals, some of the effector CD4+ T cells get infected with HIV-1. Upon fulfillment of their effector functions, almost all activated CD4+ T cells are committed to apoptosis or programmed cell death, but a minuscule fraction revert to quiescence and become resting memory CD4+ T cells to mediate a rapid immunological response against the same antigen in the future. However, due to the quiescent nature of the resting memory T cells, the integrated HIV-1 becomes transcriptionally silent and acquires a latent phenotype. Following re-exposure to the same antigen, memory cells and integrated HIV-1 are stimulated. The reactivated latent HIV provirus subsequently proceeds through its life cycle and eventually leads to the production of new viral progeny. Recently, many strategies against HIV-1 latency have been developed and some of them have even matured to the clinical level, but none can yet effectively eliminate the latent HIV reservoir, which remains a barrier to HIV-1 cure. Therefore, alternative strategies to eradicate latent HIV need to be considered. This review provides vital knowledge on HIV latency and on strategies to supplement highly active antiretroviral therapy (HAART) with cytokine-mediated therapeutics for dislodging the latent HIV reservoirs so as to open up new avenues for curing HIV. 


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