Functional characterization of core genes from patients with acute hepatitis C virus infection

Tang, X., Wagoner, J., Negash, A., Austin, M., McLauchlan, J., Hahn, Y. S., Rosen, H. R. and Polyak, S. J. (2010) Functional characterization of core genes from patients with acute hepatitis C virus infection. Journal of Infectious Diseases, 201(6), pp. 912-922. (doi:10.1086/650699) (PMID:20170366) (PMCID:PMC2827820)

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Abstract

Background. The hepatitis C virus (HCV) core protein is implicated in diverse aspects of HCV-induced pathogenesis. There is a paucity of information on core in acute hepatitis C infection.

Methods. We analyzed core gene sequences and protein functions from 13 patients acutely infected with HCV genotype 1.

Results. Although core isolates differed slightly between patients, core quasispecies were relatively homogeneous within each patient. In 2 of 4 patients studied temporally, core quasispecies did not change over time. Comparison with more than 2700 published core isolates indicated that amino acid changes from a prototype reference strain found in acute core isolates were present in chronically infected persons at low frequency (6.4%; range, 0%-32%). Core isolates associated with lipid droplets to similar degrees in Huh7 cells. Core diffusion in cells was not affected by nonconservative changes F130L and G161S in the lipid targeting domain of core. Core isolates inhibited interferon-stimulated response element- and nuclear factor κB-dependent transcription and tumor necrosis factor α-induced nuclear translocation of nuclear factor κB and were also secreted from Huh7 cells.

Conclusions. The data suggest that upon transmission, core quasispecies undergo genetic homogenization associated with amino acid changes that are rarely found in chronic infection and that, despite genetic variation, acute core isolates retain similar functions in vitro.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:McLauchlan, Professor John
Authors: Tang, X., Wagoner, J., Negash, A., Austin, M., McLauchlan, J., Hahn, Y. S., Rosen, H. R., and Polyak, S. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Infectious Diseases
Journal Abbr.:J Infect Dis.
ISSN:0022-1899
ISSN (Online):1537-6613
Published Online:05 February 2010

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656341Virus-host interactions in hepatitis C virus infectionJohn MclauchlanMedical Research Council (MRC)MC_UU_12014/1MVLS III - CENTRE FOR VIRUS RESEARCH