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 Citations (Scopus)

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 (K 9 to R or N 11 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 - 2002
Externally publishedYes

Fingerprint

Hepacivirus
Genotype
Proteins
Viruses
Virus Diseases
Missense Mutation
Amino Acid Substitution
Taiwan
Hepatitis C virus nucleocapsid protein
Transcription Factors
Cell Proliferation
Genome
Amino Acids
Mutation
Infection

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Virology

Cite this

Distinct functional role of hepatitis C virus core protein on NF-κB regulation is linked to genomic variation. / Ray, Ratna B.; Steele, Robert; Basu, Arnab; Meyer, Keith; Majumder, Mainak; Ghosh, Asish K.; Ray, Ranjit.

In: Virus Research, Vol. 87, No. 1, 2002, p. 21-29.

Research output: Contribution to journalArticle

Ray, Ratna B. ; Steele, Robert ; Basu, Arnab ; Meyer, Keith ; Majumder, Mainak ; Ghosh, Asish K. ; Ray, Ranjit. / Distinct functional role of hepatitis C virus core protein on NF-κB regulation is linked to genomic variation. In: Virus Research. 2002 ; Vol. 87, No. 1. pp. 21-29.
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