TY - JOUR
T1 - Distinct functional role of hepatitis C virus core protein on NF-κB regulation is linked to genomic variation
AU - Ray, Ratna B.
AU - Steele, Robert
AU - Basu, Arnab
AU - Meyer, Keith
AU - Majumder, Mainak
AU - Ghosh, Asish K.
AU - Ray, Ranjit
N1 - Funding Information:
We thank Michael M.C. Lai for providing the core plasmid DNA from HCV genotype 1b (Taiwan), S. Ghosh for providing NF-κB- luciferase reporter gene, and Lin Cowick for preparation of this manuscript. Our research was supported by grants AI 45144, CA85486 from the National Institutes of Health.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - Core protein
KW - Hepatitis C virus
KW - In vitro translation
KW - NF-κB regulation
KW - Substitution mutations
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U2 - 10.1016/S0168-1702(02)00046-1
DO - 10.1016/S0168-1702(02)00046-1
M3 - Article
C2 - 12135786
AN - SCOPUS:0036064441
SN - 0168-1702
VL - 87
SP - 21
EP - 29
JO - Virus Research
JF - Virus Research
IS - 1
ER -