HIV induces TRAIL sensitivity in hepatocytes.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
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.
Babu
Challagundla K
CK
Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota, United States of America.
Suwansrinon
Kanitta
K
Bren
Gary D
GD
Badley
Andrew D
AD
Rizza
Stacey A
SA
D015153:Blotting, Western; D002460:Cell Line; D005434:Flow Cytometry; D006678:HIV / Q000502:physiology*; D015699:HIV Envelope Protein gp120 / Q000502:physiology; D022781:Hepatocytes / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D011494:Protein Kinases / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation
C527276:CXCR4 protein, human; D015699:HIV Envelope Protein gp120; D019718:Receptors, CXCR4; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D011494:Protein Kinases