Cell transformation induced by hepatitis C virus NS3 serine protease

R. Zemel, S. Gerechet, H. Greif, L. Bachmatove, Y. Birk, A. Golan-Goldhirsh, M. Kunin, Y. Berdichevsky, I. Benhar, R. Tur-Kaspa*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

Persistent infection with hepatitis C virus (HCV) may lead to hepatocellular carcinoma (HCC). It has been suggested that HCV-encoded proteins are directly involved in the tumorigenic process. The HCV nonstructural protein NS3 has been identified as a virus-encoded serine protease. To study whether HCV NS3 has oncogenic activity, nontumorigenic rat fibroblast (RF) cells were stably transfected with an expression vector containing cDNA for the NS3 serine protease (nucleotides 3356-4080). The NS3 serine protease activity was determined in the transfected cells. The transfected cells grew rapidly and proliferated serum independently, lost contact inhibition, grew anchorage independently in soft agar and induced significant turnout formation in nude mice. Cells transfected with an expression vector containing a mutated NS3 serine protease (serine 139 to alanine at the catalytic site) showed no transforming abilities; their growth was dependent on serum and they did not grow anchorage independently in soft agar. Moreover, cells transfected with the NS3 serine protease and treated with the chymotrypsln inhibitors TPCK and PMSF (a serine protease inhibitor) lost their transforming feature. These results suggest that the NS3 serine protease of HCV is involved in cell transformation and that the ability to transform requires an active enzyme.

Original languageEnglish
Pages (from-to)96-102
Number of pages7
JournalJournal of Viral Hepatitis
Volume8
Issue number2
DOIs
StatePublished - 2001

Keywords

  • Hepatitis C virus
  • NS3
  • Serine protease
  • Transformation

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