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Inflammasomes as mediators of inflammation in HIV-1 infection

      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.

      Abbreviations:

      HIV (human immunodeficiency virus), SIV (simian immunodeficiency virus), AIDS (acquired immune deficiency syndrome), CCR5 (chemokine receptor 5), CXCR4 (chemokine receptor 4), ART (antiretroviral), PWH (people with HIV), CTL (cytolytic T lymphocytes), Th (T helper), PD-1 (programmed cell death protein 1), LAG-3 (lymphocyte-activation gene 3), TIGIT (T cell immunoreceptor with Ig and ITIM domains), GALT (gut-associated lymphoid tissue), LPS (lipopolysaccharide), HCV (hepatitis C virus), HBV (hepatitis B virus), CMV (cytomegalovirus), PRR (pattern recognition receptor), ASC (apoptosis-associated speck-like protein containing a caspase-recruitment domain), NLR (NOD-like receptors), NACHT (central nucleotide-binding oligomerization), ALR (AIM2-like receptors), AIM2 (absent from melanoma 2), PAMP (pathogen-associated molecular pattern), DAMP (danger-associated molecular patterns)
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