title: Exposure to low infective doses of HCV induces cellular immune responses without consistently detectable viremia or seroconversion in chimpanzees.
abstract: In hepatitis C virus (HCV) infection, there is accumulating data suggesting the presence of cellular immune responses to HCV in exposed but seemingly uninfected populations. Some studies have suggested cross-reactive antigens rather than prior HCV exposure as the main reason for the immune responses. In this study we address this question by analyzing the immune response of chimpanzees that have been sequentially exposed to increasing doses of HCV virions. The level of viremia, as well as the immune responses to HCV at different times after virus inoculation, were examined. Our data indicate that HCV infective doses as low as 1-10 RNA (+) virions induce detectable cellular immune responses in chimpanzees without consistently detectable viremia or persistent seroconversion. However, increasing the infective doses of HCV to 100 RNA (+) virions overcame the low-inoculum-induced immune response and produced high-level viremia followed by seroconversion.
authors.affiliation: New York Blood Center, New York, NY 10021, USA. mohamed_shata@NYBC.org
authors.forename: Mohamed Tarek
authors.initials: MT
authors.lastname: Shata
authors.forename: Nancy
authors.initials: N
authors.lastname: Tricoche
authors.forename: Marion
authors.initials: M
authors.lastname: Perkus
authors.forename: Darley
authors.initials: D
authors.lastname: Tom
authors.forename: Betsy
authors.initials: B
authors.lastname: Brotman
authors.forename: Patricia
authors.initials: P
authors.lastname: McCormack
authors.forename: Wolfram
authors.initials: W
authors.lastname: Pfahler
authors.forename: Dong-Hun
authors.initials: DH
authors.lastname: Lee
authors.forename: Leslie H
authors.initials: LH
authors.lastname: Tobler
authors.forename: Michael
authors.initials: M
authors.lastname: Busch
authors.forename: Alfred M
authors.initials: AM
authors.lastname: Prince
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D006526:Hepatitis C / Q000276:immunology* / Q000821:virology; D018937:Hepatitis C Antibodies / Q000097:blood; D006801:Humans; D007111:Immunity, Cellular; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism; D008213:Lymphocyte Activation; D002679:Pan troglodytes; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load; D014766:Viremia / Q000821:virology; D014774:Virulence
chemical_list: D018937:Hepatitis C Antibodies; D012367:RNA, Viral; D007371:Interferon-gamma