Rapid Loss of CD4 T Cells by Pyroptosis during Acute SIV Infection in Rhesus Macaques.
Xuan HeMalika AidJohn D VenturaErica BorducchiMichelle LiftonJinyan LiuDan H BarouchPublished in: Journal of virology (2022)
The mechanisms underlying depletion of CD4 T cells during acute HIV-1 infection are not well understood. Here we show that caspase-1-induced pyroptosis, a highly inflammatory programmed cell death pathway, is the dominant mechanism responsible for the rapid depletion of CD4 T cells in gut-associated lymphatic tissue (GALT), spleen, and lymph nodes during acute simian immunodeficiency virus (SIV) infection in rhesus macaques. Upregulation of interferon-gamma inducible factor 16, a host DNA sensor that triggers pyroptosis, was also observed in tissue-resident CD4 T cells and correlated with viral loads and CD4 T cell loss. In contrast, caspase-3-mediated apoptosis and viral cytotoxicity only accounted for a small fraction of CD4 T cell death. Other programmed cell death mechanisms, including mitochondria-induced caspase-independent cell death, necroptosis, and autophagy, did not significantly contribute to CD4 T cell depletion. These data support a model in which caspase-1-mediated pyroptosis is the principal mechanism that results in CD4 T cell loss in the GALT and lymphoid organs and release of proinflammatory cytokines. These findings contribute to our understanding of the pathogenesis of acute SIV infection and have important implications for the development of therapeutic strategies. IMPORTANCE Different mechanisms for CD4 T cell depletion during acute HIV-1 infection have been proposed. In this study, we demonstrate that in early simian immunodeficiency virus infection, depletion of CD4 T cells is primarily due to pyroptosis. Other mechanisms may also contribute in a minor way to CD4 T cell depletion.
Keyphrases
- cell death
- liver failure
- drug induced
- respiratory failure
- lymph node
- nlrp inflammasome
- cell cycle arrest
- aortic dissection
- sars cov
- induced apoptosis
- hepatitis b virus
- high glucose
- single molecule
- oxidative stress
- big data
- patient safety
- endoplasmic reticulum stress
- antiretroviral therapy
- endoplasmic reticulum
- computed tomography
- electronic health record
- quality improvement
- circulating tumor cells
- reactive oxygen species
- emergency medicine
- circulating tumor
- data analysis
- stress induced
- loop mediated isothermal amplification