Teasing apart the cell death pathways in HIV pathogenesis

Abstract

The progressive loss of CD4 + T cells has been recognised as being central to HIV-1 pathogenesis, however a precise understanding of the underlying mechanisms and, consequently, improved therapies have yet to be achieved. Zhang et al. have recently shown in HIV-1 patients that the NLRP3 inflammasome pathway, which plays a key role in innate immunity, is a crucial mediator of the loss of CD4 + T cells. This advance could inform the development of innovative anti-HIV-1 therapies.

Race between virus and inflammasomes: inhibition or escape, intervention and therapy

“…On the one hand, NLRP3 inflammasome enhance the body's ability to clear the virus at the initial stage of HIV-1 infection as described by Reis et al (2019). On the other hand, NLRP3 inflammasome promotes pyroptosis of "bystander" CD4 + T cells (Montague-Cardoso, 2021;Zhang C. et al, 2021) and causes brain disease and neuroinflammation that are closely associated with NLRP3 inflammasome activation in microglia (Walsh et al, 2014;He et al, 2020). Finally, surprisingly, Paoletti et al demonstrated that HIV-1 induces NLRP3 degradation through purinergic receptor (P2Y2) signaling pathway, suggesting that HIV-1 has evolved an NLRP3-mediated immune escape strategy (Paoletti et al, 2019).…”

“…(2019) . On the other hand, NLRP3 inflammasome promotes pyroptosis of “bystander” CD4 + T cells ( Montague-Cardoso, 2021 ; Zhang C. et al., 2021 ) and causes brain disease and neuroinflammation that are closely associated with NLRP3 inflammasome activation in microglia ( Walsh et al., 2014 ; He et al., 2020 ). Finally, surprisingly, Paoletti et al.…”