HIV Induces TRAIL Sensitivity in Hepatocytes

• DOI: 10.1371/journal.pone.0004623
• Publication Date: 2009-02-26T19:09:14Z
• Authors: Challagundla K. Babu; Kanitta Suwansrinon; Gary D. Bren; Andrew D. Badley; Stacey A. Rizza
• Keywords: 0301 basic medicine; Receptors, CXCR4; Science; Q; Blotting, Western; R; HIV; HIV Envelope Protein gp120; Flow Cytometry; Cell Line; Up-Regulation; 3. Good health; TNF-Related Apoptosis-Inducing Ligand; 03 medical and health sciences; Hepatocytes; Medicine; Humans; Protein Kinases; Research Article; Signal Transduction

HIV infected patients have an increased susceptibility to liver disease due to Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), alcoholic, and non-alcoholic steatohepatitis. Clinically, this results in limited options for antiretroviral therapy and accelerated rates of liver disease, causing liver disease to be the second leading cause of death for HIV infected patients. The mechanisms causing this propensity for liver dysfunction during HIV remains unknown.We demonstrate that HIV and/or the HIV glycoprotein gp120 ligation of CXCR4 on hepatocytes selectively up-regulates TRAIL R2 expression and confers an acquired sensitivity to TRAIL mediated apoptosis which is mediated by JNK II, but not p38 nor G-proteins.These findings suggest that HIV infection renders hepatocytes more susceptible to liver injury during disease states associated with enhanced TRAIL production such as HBV, HCV, or steatohepatitis.