TRAILshort Protects against CD4 T Cell Death during Acute HIV Infection.
Sekar NatesampillaiAna C PaimNathan W CumminsAswath P ChandrasekarGary D BrenSharon R LewinHans-Peter KiemAndrew D BadleyPublished in: Journal of immunology (Baltimore, Md. : 1950) (2019)
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.
Keyphrases
- antiretroviral therapy
- hiv infected
- cell death
- hiv infected patients
- human immunodeficiency virus
- hiv positive
- cell cycle arrest
- hiv aids
- drug induced
- liver failure
- high glucose
- endothelial cells
- end stage renal disease
- signaling pathway
- respiratory failure
- induced apoptosis
- ejection fraction
- chronic kidney disease
- gene expression
- newly diagnosed
- intensive care unit
- weight gain
- genome wide
- oxidative stress
- aortic dissection
- pi k akt
- patient reported outcomes
- cell proliferation
- acute respiratory distress syndrome