UC San Diego

Antiretroviral therapy (ART) has ameliorated substantially human immunodeficiency virus type 1 (HIV-1) associated disease. Even so, persons living with HIV-1 (PLWH) on ART still exhibit chronic inflammation and various forms of HIV-1-associated disorders. The continued existence of HIV-1-associated disorders is thought to result from persistent inflammation present in PLWH despite sustained viral suppression and normalization of the CD4+ T cell count. Recent literature suggests that inflammasome activation is central to persistent inflammation with the NLRP3 inflammasome being the most studied. Upon formation of the NLRP3 inflammasome complex, the cytokines IL-1β and IL-18 are produced. PLWH have increased activation of the complex that results in excess cytokine production, causing excessive inflammation. This activation is thought to contribute to a broad range of associated diseases including the early onset of aging, cardiovascular disease, and cognitive disorders. In this review, the mechanisms associated with the activation of the NLRP3 inflammasome in HIV-1 infected cells as well as the role of NLRP3 in persistent inflammation and HIV-associated pathogenesis are discussed. A summary of the NLRP3 inflammasome in HIV pathogenesis and inflammation as well as its role in other diseases will be given. Consequently, possible therapeutics using NLRP3 inflammasome inhibitors will also be discussed. By understanding the NLRP3 inflammasome and its connection to HIV-1, effective methods to treat HIV-1-associated diseases caused by excessive inflammation can be identified.