Studies of Viral Hepatitis and AIDS in the Chimpanzee Model

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Abstract

This laboratory was the first to transmit non-A, non-B hepatitis (subsequently proved to be hepatitis C) and human immunodeficiency virus (HIV) to the chimpanzee and hence to establish an animal model for these infections. Current studies in this model include the following: oThe Early Events of HIV Infection: In this study a chimpanzee was infected with HIV and serial apheresis units were obtained during the window period between exposure and the first detection of anti-HIV antibody. It was shown that no markers of HIV infection were detectable until the fifth week post-exposure, at which time virus was detectable by HIV RNA, HIV DNA, and viral culture. Anti-HIV and p24 antigen, routinely used in blood donor screening, were not detectable until 8 weeks post-exposure. Subsequently, the 3-, 4-, and 5-week samples were sequentially inoculated into a second chimp. The 3- and 4-week samples were shown to be non-infectious while the 5-week sample was infectious. Hence, infectivity did not precede the detection of HIV RNA and DNA. This suggests that if molecular assays for HIV were introduced into blood screening they might totally abrogate the infectious window and prevent blood transmission of HIV. Similar studies are now being performed for hepatitis C virus (HCV) infection to determine if nucleic acid testing (NAT) of donors could completely block HCV transmission. oViral Inactivation: In collaboration with Cerus Corp., the chimp model was used to establish the efficacy of psoralen/UV-inactivated platelets. This is the first viral inactivation procedure that maintains the integrity of the cellular components of blood. Three chimpanzees have each been exposed to infectious doses of HCV and hepatitis B virus (HBV) that have been psoralen-UV treated. After one year of follow-up, no animal was infected with either HBV or HCV. This study is now being repeated with psoralen-UV inactivated plasma. These animal studies confirm in vitro efficacy data and set the stage for safety and efficacy trials in humans. This method should have broad application for platelet transfusion therapy, and ultimately, for plasma and red cell transfusion as well.