Peer-Reviewed Journal Details
Mandatory Fields
Stevenson, NJ,Bourke, NM,Ryan, EJ,Binder, M,Fanning, L,Johnston, JA,Hegarty, JE,Long, A,O'Farrelly, C
2013
May
Febs Letters
Hepatitis C virus targets the interferon-alpha JAK/STAT pathway by promoting proteasomal degradation in immune cells and hepatocytes
Validated
Optional Fields
Hepatitis C Virus Interferon JAK/STAT Ubiquitination Proteasome SIGNALING PATHWAY STAT3 ACTIVATION EXPRESSION INFECTION PROTEINS MICE DISRUPTION LIVER LEADS GENE
587
1571
1578
JAK/STAT signalling is essential for anti-viral immunity, making IFN-alpha an obvious anti-viral therapeutic. However, many HCV+ patients fail treatment, indicating that the virus blocks successful IFN-alpha signalling. We found that STAT1 and STAT3 proteins, key components of the IFN-alpha signalling pathway were reduced in immune cells and hepatocytes from HCV infected patients, and upon HCV expression in Huh7 hepatocytes. However, STAT1 and STAT3 mRNA levels were normal. Mechanistic analysis revealed that in the presence of HCV, STAT3 protein was preferentially ubiquitinated, and degradation was blocked by the proteasomal inhibitor MG132. These findings show that HCV inhibits IFN-alpha responses in a broad spectrum of cells via proteasomal degradation of JAK/STAT pathway components. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
10.1016/j.febslet.2013.03.041
Grant Details