Functional characterization of core genes from patients with acute hepatitis C virus infection.
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 kappaB-dependent transcription and tumor necrosis factor alpha-induced nuclear translocation of nuclear factor kappaB 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.
Tang
Xi
X
Departments of Laboratory Medicine, University of Washington, Seattle, WA 98104, USA.
Wagoner
Jessica
J
Negash
Amina
A
Austin
Michael
M
McLauchlan
John
J
Hahn
Young S
YS
Rosen
Hugo R
HR
Polyak
Stephen J
SJ
D000208:Acute Disease; D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D005260:Female; D014644:Genetic Variation; D016174:Hepacivirus / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity*; D006526:Hepatitis C / Q000821:virology*; D006801:Humans; D008055:Lipids / Q000502:physiology; D008297:Male; D008969:Molecular Sequence Data; D010802:Phylogeny; D012367:RNA, Viral; D014758:Viral Core Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D014861:Washington
D008055:Lipids; D012367:RNA, Viral; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus