The Role of Inflammasome Activation in Early HIV Infection

Figure 1

An illustration of the NLRP3 activation in HIV infection, and how HIV evades the NLRP3 inflammasome pathway. HIV infects target cells by interacting with CD4 receptors and coreceptors CXCR4/CCR5, which leads to the activation of the purinergic pathway via an increase in extracellular ATP and potassium ion [K+] efflux. Interaction between the activated purinergic receptor (P2Y2) and NLRP3 leads to activation of NLRP3 inflammasome which triggers acute inflammation, pyroptosis (via Gasdermin D), and inhibition of HIV entry. However, HIV evades the NLRP3 inflammasome pathway by activating the release of E3 ubiquitin ligase which ubiquitinates NLRP3 leading to proteasomal degradation. Also, abortive HIV infection of resting CD4 T cells triggers NLRP3-mediated pyroptosis which accounts for majority of CD4 T cell depletion and sustained inflammation.