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Review
. 2023 Feb:252:1-8.
doi: 10.1016/j.trsl.2022.07.008. Epub 2022 Jul 30.

Inflammasomes as mediators of inflammation in HIV-1 infection

Alice K Min  1 , Trinisia Fortune  1 , Natalia Rodriguez  1 , Esha Hedge  2 , Talia H Swartz  3
Affiliations
Review

Inflammasomes as mediators of inflammation in HIV-1 infection

Alice K Min et al. Transl Res. 2023 Feb.

Abstract

Human immunodeficiency virus type 1 (HIV-1) infection is a chronic disease without a known cure. The advent of effective antiretroviral therapy (ART) has enabled people with HIV (PWH) to have significantly prolonged life expectancies. As a result, morbidity and mortality associated with HIV-1 infection have declined considerably. However, these individuals experience chronic systemic inflammation whose multifaceted etiology is associated with other numerous comorbidities. Inflammasomes are vital mediators that contribute to inflammatory signaling in HIV-1 infection. Here, we provide an overview of the inflammatory pathway that underlies HIV-1 infection, explicitly highlighting the role of the NLRP3 inflammasome. We also delineate the current literature on inflammasomes and the therapeutic targeting strategies aimed at the NLRP3 inflammasome to moderate HIV-1 infection-associated inflammation. Here we describe the NLRP3 inflammasome as a key pathway in developing novel therapeutic targets to block HIV-1 replication and HIV-1-associated inflammatory signaling. Controlling the inflammatory pathways is critical in alleviating the morbidities and mortality associated with chronic HIV-1 infection in PWH.

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Figures

Figure 1.
Figure 1.. NLRP3 Inflammasome signaling pathway and the therapeutic targets.
HIV-1 infection is associated with the production of PAMPs/DAMPs detected by stress-sensing sensors and activating downstream inflammasome signaling. For example, LPS is detected by toll-like receptors (TLR) that stimulate NF-kB-dependent transcription of NLRP3 inflammasome precursor genes: nlrp3, pro-IL-1β, pro-IL-18, and casp1. Simultaneously, extracellular ATP released by HIV-1 infected cells is detected by selective P2X purinergic receptors, leading to potassium ion efflux and calcium ion influx and activating the NLRP3 inflammasome assembly. Activated caspase-1 cleaves pro-IL-1β and pro-IL-18 into mature, secretory IL-1β and IL-18 that induce pyroptosis or proinflammatory programmed cell death. Dotted red boxes represent compounds that inhibit the NLRP3 inflammasome. These compounds act either directly by binding to the NLRP3 inflammasome complex or indirectly by acting on a component that is either upstream or downstream of the NLRP3 inflammasome in the signaling pathway. (PAMP, pathogen-associated molecular pattern; DAMP, damage-associated molecular pattern; LPS, lipopolysaccharide). Created with BioRender.com.
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