Chronic hepatitis C virus infection established and maintained in chimpanzees independent of dendritic cell impairment.
Chronic hepatitis C virus (HCV) infection in humans is associated with an impairment of dendritic cells (DC). It has been hypothesized that impairment of DC function may be a central mechanism facilitating the establishment of a chronic carrier state. However, the majority of patients studied with DC impairment to date have been identified and, thus, inadvertently selected because of clinical manifestations leading to their diagnosis, which may have been many years following actual infection. We set out to determine whether impaired DC function occurred in the earlier asymptomatic phase of infection and turned to a well-defined cohort of HCV-infected chimpanzees in which the specific date of infection and the nature of the inoculum were well characterized. Results revealed that, in contrast to the observations in human subjects with advanced clinical hepatitis, there was neither impairment of the allostimulatory capacity of monocyte-derived DC from HCV chronic carriers nor impairment of the maturation process. Decreased allostimulatory capacity was only detected in 2 animals and, interestingly, in those that possessed the highest viral loads. Nevertheless, HCV sequences were undetectable in any of the DC derived from HCV-infected chimpanzees. In conclusion, these findings suggest that the mechanisms of establishing persistent HCV infection are separate and independent from those responsible for impaired DC function. Indeed, the maturation and allostimulatory impairment, as described in patient studies, are not necessary prerequisites but rather possible consequences of persistent and active HCV infection associated with disease progression.
D000818:Animals; D018420:Ape Diseases / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000502:physiology* / Q000821:virology; D004705:Endocytosis; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000276:immunology / Q000662:veterinary* / Q000821:virology; D006801:Humans; D016130:Immunophenotyping; D008297:Male; D002679:Pan troglodytes / Q000821:virology*