TRAILshort Protects against CD4 T Cell Death during Acute HIV Infection
Year: 2019
Type: article
Abstract: CD4 T cells from HIV-1 infected patients die at excessive rates compared to those from uninfected patients, causing immunodeficiency. We previously identified a dominant negative ligand that antagonizes the TRAIL-dependent pathway of cell death, which we called TRAILshort. Because the TRAIL pathway has been implicated in CD4 T cell death occurring during HIV-1 infection, we used short hairpin RNA knockdown, CRISPR deletion, or Abs specific for TRAILshort to determine the effect of inhibiting TRAILshort on the outcome of experimental acute HIV infection in vitro. Strikingly, all three approaches to TRAILshort deletion/inhibition enhanced HIV-induced death of both infected and uninfected human CD4 T cells. Thus, TRAILshort impacts T cell dynamics during HIV infection, and inhibiting TRAILshort causes more HIV-infected and uninfected bystander cells to die. TRAILshort is, therefore, a host-derived, host-adaptive mechanism to limit the effects of TRAIL-induced cell death. Further studies on the effects of TRAILshort in other disease states are warranted.
Source: The Journal of Immunology
Language: English
Topic: HIV Research and Treatment
Subfield: Virology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Awards: Evaluating the role of the novel apoptosis inhibitor TRAILshort, in maintaining HIV persistence., DARE: Delaney AIDS Research Enterprise to find a cure., Prime shock and kill for HIV erradication, Delaney AIDS Research Enterprise to Cure HIV, Evaluating the role of the novel apoptosis inhibitor TRAILshort, in maintaining HIV persistence
OpenAlex ID: W2949933606