Early Phase of Specific Cellular Immune Status Associates with HCV Infection Outcomes in Marmosets

Abstract

The major mechanism for determination of HCV infection outcomes has not been fully described, particularly in the early phase of the “window-period” of infection. Based on two groups of marmosets infected with HCV-CE1E2p7/GBV-B chimeric virus (HCV chimera) or GBV-B, the immune mechanism correlating with the different outcomes of virus infections was explored in this study. HCV chimera containing the entire HCV core and envelope proteins (CE1E2p7) and GBV-B RNA were intrahepatically injected into four marmosets in each group, respectively. Blood samples were taken from individual animals in an interval of 2 weeks. Viral load and specific T cell responses were detected in two groups of HCV chimera- and GBV-B-infected marmosets. HCV chimera-infected marmosets appeared to have a virally persistent infection over 6 months post inoculation of the virus. Of these, the specific IFN-γ-secretion T cell response slowly developed over 13 to 19 weeks and was maintained at a relatively low level with 40–70 SFC/106 PBMCs, while the specific Treg cell response was rapidly activated over 3 weeks and was maintained at a high level around 5% among lymphocytes. In contrast, GBV-B-infected marmosets presented spontaneous viral clearance within 6 months; the specific IFN-γ-secretion T cell response was quickly established over 5 to 7 weeks and was maintained at a high level with 50–130 SFC/106 PBMCs, while the specific Treg cell response was inactivated and maintained at a baseline below 3% among lymphocytes. In conclusion, the HCV structural proteins inducing immune suppression in the early phase of HCV infection contributed to the viral persistence, of which the activation of Treg cells might play an important role in the inhibition of an effective T cell antiviral response.

Marmosets as models of infectious diseases

“…Tregs, a unique type of CD4+ T cell with suppressor functions, are important in maintaining immune tolerance (Sakaguchi et al, 2008). In the context of an infection, Tregs can modulate effector T cell responses and, by inhibiting the anti-viral functions of specific T cells, may permit viral persistence (Boer et al, 2015;Liu et al, 2023). In chronically infected individuals, Treg populations are maintained, whereas the suppressor function of Tregs was diminished in individuals with acute resolving infection (Liu et al, 2023).…”

“…In the context of an infection, Tregs can modulate effector T cell responses and, by inhibiting the anti-viral functions of specific T cells, may permit viral persistence (Boer et al, 2015;Liu et al, 2023). In chronically infected individuals, Treg populations are maintained, whereas the suppressor function of Tregs was diminished in individuals with acute resolving infection (Liu et al, 2023). The phenotype and role of Tregs in the marmoset is yet to be determined.…”