Current strategies to induce selective killing of HIV-1-infected cells

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

article

Grant R. Campbell¹  Stephen A. Spector¹ 

[1] Department of Pediatrics, Division of Infectious Diseases, University of California San Diego;Division of Infectious Diseases, Rady Children's Hospital

关键词: HIV-1;    IAP;    cell death;    SMAC mimetics;    autophagy;    apoptosis;    autosis;   

DOI  :  10.1002/JLB.4MR0422-636R

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Although combination antiretroviral therapy (ART) has led to significant HIV-1 suppression and improvement in immune function, persistent viral reservoirs remain that are refractory to intensified ART. ART poses many challenges such as adherence to drug regimens, the emergence of resistant virus, and cumulative toxicity resulting from long-term therapy. Moreover, latent HIV-1 reservoir cells can be stochastically activated to produce viral particles despite effective ART and contribute to the rapid viral rebound that typically occurs within 2 weeks of ART interruption; thus, lifelong ART is required for continued viral suppression. Several strategies have been proposed to address the HIV-1 reservoir such as reactivation of HIV-1 transcription using latency reactivating agents with a combination of ART, host immune clearance and HIV-1-cytotoxicity to purge the infected cells—a “shock and kill” strategy. However, these approaches do not take into account the multiple transcriptional and translational blocks that contribute to HIV-1 latency or the complex heterogeneity of the HIV-1 reservoir, and clinical trials have thus far failed to produce the desired results. Here, we describe alternative strategies being pursued that are designed to kill selectively HIV-1-infected cells while sparing uninfected cells in the absence of enhanced humoral or adaptive immune responses.

【 授权许可】

CC BY