Role of inflammasomes in HIV-1 infection and treatment

Multiple inflammasomes, including NLR family pyrin domain-containing protein 3 (NLRP3), caspase recruitment domain-containing protein 8 (CARD8), interferon-inducible protein 16 (IFI16), NLRP1, NLR family CARD domain-containing 4 (NLRC4), and absent in melanoma 2 (AIM2), are involved in HIV-1 infection-induced inflammation and their mediated pyroptosis contributes to CD4+ T cell loss. Several components of HIV-1, such as abortive HIV-1 RNAs, viral protein R (Vpr), gp120, transactivator of transcription (Tat), and HIV-1 protease, can trigger inflammasome activation. CARD8 is a direct inflammasome sensor for HIV-1 protease activity, mediating pyroptosis of HIV-1-infected cells. NLRP3 inflammasome-mediated pyroptosis contributes to CD4+ T cell loss in patients with HIV-1. Although combined antiretroviral therapy (cART) is effective in inhibiting human immunodeficiency virus type 1 (HIV-1) replication, it does not eradicate the virus because small amounts of latent HIV-1 provirus persist in quiescent memory CD4+ T cells. Therefore, strategies for eradicating latent HIV-1 are urgently needed. Recently, several studies have reported that the inflammatory response and lymphocyte death induced by HIV-1 depend on inflammasomes and pyroptosis, suggesting that inflammasomes and pyroptosis have a vital role in HIV-1 infection and contribute to the eradication of latent HIV-1. In this review, we summarize current knowledge of the role of inflammasomes, including NLR family pyrin domain-containing protein 3 (NLRP3), caspase recruitment domain-containing protein 8 (CARD8), interferon-inducible protein 16 (IFI16), NLRP1, NLR family CARD domain-containing 4 (NLRC4), and absent in melanoma 2 (AIM2), in HIV-1 infection and discuss promising therapeutic strategies for HIV-1-associated diseases by targeting inflammasomes. Although combined antiretroviral therapy (cART) is effective in inhibiting human immunodeficiency virus type 1 (HIV-1) replication, it does not eradicate the virus because small amounts of latent HIV-1 provirus persist in quiescent memory CD4+ T cells. Therefore, strategies for eradicating latent HIV-1 are urgently needed. Recently, several studies have reported that the inflammatory response and lymphocyte death induced by HIV-1 depend on inflammasomes and pyroptosis, suggesting that inflammasomes and pyroptosis have a vital role in HIV-1 infection and contribute to the eradication of latent HIV-1. In this review, we summarize current knowledge of the role of inflammasomes, including NLR family pyrin domain-containing protein 3 (NLRP3), caspase recruitment domain-containing protein 8 (CARD8), interferon-inducible protein 16 (IFI16), NLRP1, NLR family CARD domain-containing 4 (NLRC4), and absent in melanoma 2 (AIM2), in HIV-1 infection and discuss promising therapeutic strategies for HIV-1-associated diseases by targeting inflammasomes. group of rare autoinflammatory disorders caused by gain-of-function mutations in NLRP3. The diseases include three clinical subtypes: familial cold autoinflammatory syndrome type 1 (FCAS1), neonatal-onset multisystem inflammatory disease (NOMID), and Muckle–Wells syndrome (MWS). diverse group of decompartmentalized molecules, including β-amyloid peptide, monosodium urate, ADT, and aluminum. They act as danger molecules to be recognized by pattern recognition receptors and initiate the immune response. HIV-1 treatment regimen, usually comprising a combination of three or more antiretroviral drugs. large, cytoplasmic, multiprotein complexes comprising innate immune receptors and the adaptor proteins ASC and caspase-1; its main function is to induce inflammatory responses and maintain homeostasis. two classes of anti-AIDS drug that inhibit reverse transcriptase activity, which blocks HIV-1 replication by inhibiting RNA conversion into DNA class of intracellular pattern recognition receptors that initiate innate immune responses upon activation by PAMPs and DAMPs; several have been found to form inflammasome, such as NLRP3, NLRC4, and NLRP6. unique class of molecules related to microorganisms, which can be recognized by pattern recognition receptors to initiate the immune response. group of disorders caused by excessive inflammation due to bacterial or viral infection, leading to fever; usually manifests between the ages of 2 and 5 years. gasdermin D (GSDMD)-dependent proinflammatory form of programmed cell death characterized by cell swelling and plasma membrane rupture; its main function is to resist pathogenic microorganism infection. (single nucleotide polymorphism) a polymorphism associated with single base variation; usually involved in human disease.