HCV core protein localizes in the nuclei of nonparenchymal liver cells from chronically HCV-infected patients.
Understanding the mechanism of hepatitis C virus (HCV) pathogenesis is an important part of HCV research. Recent experimental evidence suggests that the HCV core protein (HCcAg) has numerous functional activities. These properties suggest that HCcAg, in concert with cellular factors, may contribute to pathogenesis during persistent HCV infection. HCV is capable of infecting cells other than hepatocytes. Although the extrahepatic cellular tropism of HCV may play a role in the pathophysiology of this infection, the precise biological significance of the presence of HCV components in different liver cell types presently remains to be established. In this study, HCcAg was detected in nonparenchymal liver cells of six patients out of eight positive for serum HCV RNA. Immunostaining with anti-HCcAg mAbs revealed the presence of this protein in different liver cell types such as lymphocytes, Kupffer, polymorphonuclear, pit, endothelial, stellate, and fibroblast-like cells. Interestingly, HCcAg was immunolabeled not only in the cytoplasm but also in the nucleus of these cells. Remarkably, HCcAg co-localized with large lipid droplets present in stellate cells and with collagen fibers in the extracellular matrix. Moreover, HCcAg was immunolabeled in bile canaliculus suggesting the involvement of the biliary system in the pathobiology of HCV. Data suggest that nonparenchymal liver cells may constitute a reservoir for HCV replication. Besides, HCcAg may contribute to modulate immune function and fibrosis in the liver as well as steatosis.
Falcón
Viviana
V
Biomedicine Division, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, C.P. 10600, Havana, Cuba. viviana.falcon@cigb.edu.cu
Acosta-Rivero
Nelson
N
Shibayama
Mineko
M
Chinea
Glay
G
Gavilondo
Jorge V
JV
de la Rosa
María C
MC
Menéndez
Ivón
I
Gra
Bienvenido
B
Dueñas-Carrera
Santiago
S
Viña
Ariel
A
García
Waldo
W
González-Bravo
Maritza
M
Luna-Munoz
Jose
J
Miranda-Sanchez
Magdalena
M
Morales-Grillo
Juan
J
Kouri
Juan
J
Tsutsumi
Victor
V
D000328:Adult; D001706:Biopsy; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D016174:Hepacivirus / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000378:metabolism* / Q000473:pathology*; D022781:Hepatocytes / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D006801:Humans; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D014758:Viral Core Proteins / Q000378:metabolism*
D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus