Hepatitis B and hepatitis C virus replication upregulates serine protease inhibitor Kazal, resulting in cellular resistance to serine protease-dependent apoptosis.
Hepatitis B and C viruses (HBV and HCV, respectively) are different and distinct viruses, but there are striking similarities in their disease potential. Infection by either virus can cause chronic hepatitis, liver cirrhosis, and ultimately, liver cancer, despite the fact that no pathogenetic mechanisms are known which are shared by the two viruses. Our recent studies have suggested that replication of either of these viruses upregulates a cellular protein called serine protease inhibitor Kazal (SPIK). Furthermore, the data have shown that cells containing HBV and HCV are more resistant to serine protease-dependent apoptotic death. Since our previous studies have shown that SPIK is an inhibitor of serine protease-dependent apoptosis, it is hypothesized that the upregulation of SPIK caused by HBV and HCV replication leads to cell resistance to apoptosis. The evasion of apoptotic death by infected cells results in persistent viral replication and constant liver inflammation, which leads to gradual accumulation of genetic changes and eventual development of cancer. These findings suggest a possibility by which HBV and HCV, two very different viruses, can share a common mechanism in provoking liver disease and cancer.
Lamontagne
Jason
J
Drexel Institute for Biotechnology and Virology Research, Department of Microbiology, Drexel University, 3805 Old Easton Road, Doylestown, PA 18902, USA.
Pinkerton
Mark
M
Block
Timothy M
TM
Lu
Xuanyong
X
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D045744:Cell Line, Tumor; D016174:Hepacivirus / Q000472:pathogenicity / Q000502:physiology*; D006515:Hepatitis B virus / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000502:physiology; D057057:Serine Proteases / Q000378:metabolism; D014359:Trypsin Inhibitor, Kazal Pancreatic; D015854:Up-Regulation; D014779:Virus Replication
D002352:Carrier Proteins; C486642:SPINK1 protein, human; D014359:Trypsin Inhibitor, Kazal Pancreatic; D057057:Serine Proteases