February 8, 2021

Key factors in HIV-1 replication

HIV-1, the virus that causes AIDS, exploits inositol phosphates in T cells to aid its own assembly and maturation — suggesting that targeting inositol phosphate binding could inhibit HIV-1 replication.

by Anivarya Kumar

HIV-1 infects T-helper cells, the white blood cell type lost in AIDS, and in the process produces more viral particles and kills the host cell. 

HIV-1 particle assembly is promoted by cellular metabolites IP5 and IP6, inositol phosphates that regulate diverse cellular functions. To determine how IP5 and IP6 influence HIV-1 replication, Gregory Sowd, PhD, and Christopher Aiken, PhD, disrupted genes essential for IP5 and IP6 production in T cell lines and studied the effects of IP5/IP6 depletion on HIV-1 replication. 

As reported in PLOS Pathogens, they found that depletion of inositol phosphates decreased HIV-1 assembly and altered maturation, leading to delayed HIV-1 spread and decreased particle infectivity relative to wild-type cells. 

The data demonstrate that IP6 is exploited by HIV-1 to orchestrate both virion assembly and maturation. The authors propose that pharmacological targeting of inositol phosphate binding with small molecules will inhibit distinct aspects of HIV-1 replication.

This study was supported by National Institutes of Health grants AI150384, AI076121 and AI150481.