Exposure to low infective doses of HCV induces cellular immune responses without consistently detectable viremia or seroconversion in chimpanzees.
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.
Shata
Mohamed Tarek
MT
New York Blood Center, New York, NY 10021, USA. mohamed_shata@NYBC.org
Tricoche
Nancy
N
Perkus
Marion
M
Tom
Darley
D
Brotman
Betsy
B
McCormack
Patricia
P
Pfahler
Wolfram
W
Lee
Dong-Hun
DH
Tobler
Leslie H
LH
Busch
Michael
M
Prince
Alfred M
AM
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
D018937:Hepatitis C Antibodies; D012367:RNA, Viral; D007371:Interferon-gamma