The anti-caspase 1 inhibitor VX-765 reduces immune activation, CD4⁺ T cell depletion, viral load, and total HIV-1 DNA in HIV-1 infected humanized mice.

ABSTRACT: HIV-1 infection results in the activation of inflammasome that may facilitate viral spread and establishment of viral reservoirs. We evaluated the effects of the caspase-1 inhibitor VX-765 on HIV-1 infection in humanized NSG mice engrafted with human CD34⁺ hematopoietic stem cells. Expression of caspase-1, NLRP3, and IL-1β was increased in lymph nodes and bone marrow between day 1 and 3 after HIV-1 infection (mean fold change (FC) of 2.08, 3.23, and 6.05, p<0.001, respectively). IFI16 and AIM2 expression peaked at day 24 and coincides with increased IL-18 levels (6.89 vs 83.19 pg/ml, p=0.004), increased viral load and CD4⁺ T cells loss in blood (p<0.005 and p<0.0001, for the spleen respectively). Treatment with VX-765 significantly reduced TNF-α at day 11 (0.47 vs 2.2

SUBMITTER: Amand M 

PROVIDER: S-EPMC9937651 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature