A model of chronic infection of primary cultures of suckling mouse bra
in (SMB) cells actively producing hepatitis C virus (HCV) is developed
. Destruction and repopulation of cells was observed for at least 6 mo
nths; this phenomenon was paralleled by virus release in culture mediu
m. Persistent HCV contained in SMB cultures induced a cytopathogenic e
ffect in PS, BHK-21, Vero, HAK, and chick embryo cell cultures, its in
fective titers being 10.0-12.0 lg TCD50/0.2 ml. Persistent HCV formed
heterogeneous plaques under agar in chick embryo cells, The polymerase
chain reaction (PCR) regularly detected the HCV RNA at the stage of c
ell destruction in the culture fluid of HCV-infected cell cultures. Th
e cytopathogenic activity of persistent HCV was neutralized by anti-HC
V positive patients' sera with the neutralization index of 8.0-9.0 lg.
The results of persistent HCV neutralization were confirmed by PCR. I
mmunofluorescence detected virus-specific HCV antigens in 15-40% of in
fected cells. Hence, the SMB-HCV system realized the cytopathogenic po
tential of HCV circulating in the blood of patients with hepatitis C.
This system is promising for the study of the pathogenesis of HCV infe
ction at a cellular level, for screening for specific and nonspecific
antiviral agents, and for preparing native virrrsspecific proteins and
RNA.