Distinct functional role of hepatitis C virus core protein on NF-κB regulation is linked to genomic variation

Ratna B. Ray, Robert Steele, Arnab Basu, Keith Meyer, Mainak Majumder, Asish K. Ghosh, Ranjit Ray

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Hepatitis C virus (HCV) often causes a prolonged and persistent infection. Sequence divergence in the HCV genome indicates several genotypes and a series of subtypes for this virus. The core protein of HCV has many intriguing functional properties and is implicated as a factor in virus mediated pathogenesis. Nuclear factor κB (NF-κB), a transcription factor, responds to inflammatory signals, activates the expression of inflammatory mediators, and plays a role in cell proliferation process. In this study, we have investigated NF-κB regulation by HCV core protein cloned from three isolates of different genotypes. Our results suggest that core protein from HCV genotype 1a represses NF-κB activation, unlike two other core genomic regions from HCV genotype 1b (BK or Taiwan). However, missense mutations in positions (K9 to R or N11 to T) of HCV genotype 1a relieve repression of NF-κB regulation by core protein. Interestingly, in vitro translation studies suggested that amino acid substitution at position 11 (N→T) in HCV genotype 1a generated a primary protein product of ∼17 kDa, smaller than the major ∼21 kDa protein band apparent in the parental sequence or with one carrying mutation at amino acid position 9 (K→R). However, the ∼17 kDa protein did not appear to be involved in NF-κB regulation. Taken together, our present data suggest that genomic variation in the core protein determines a distinct functional regulation of NF-κB, which may modulate immunnoregulatory molecules early in viral infection.

Original languageEnglish (US)
Pages (from-to)21-29
Number of pages9
JournalVirus Research
Volume87
Issue number1
DOIs
StatePublished - Aug 3 2002

Keywords

  • Core protein
  • Hepatitis C virus
  • In vitro translation
  • NF-κB regulation
  • Substitution mutations

ASJC Scopus subject areas

  • Cancer Research
  • Virology
  • Infectious Diseases

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