This laboratory was the first to transmit non-A and non-B hepatitis (subsequently proved to be hepatitis C) and HIV to the chimpanzee and hence establish an animal model for these infections. Current studies in this model include the following: (1) The Early Events of HIV Infection. In this study a chimpanzee was infected with HIV and serial apheresis units were obtained during the period between exposure and first detection of anti-HIV antibody. It was shown that no markers of HIV infection were detectable until the fifth week after exposure when the virus was detectable by measurement of HIV RNA, HIV DNA, and viral culture. In contrast, anti-HIV and p24 antigen, as used in blood donor screening, were not detectable until 8 weeks after exposure. In a second phase of the experiment, the 3-, 4-, and 5-week samples were sequentially inoculated into a second chimp. The 3- and 4-week samples were shown to be noninfectious while the 5-week sample was infectious. Hence, infectivity did not precede the detection of HIV RNA and DNA, suggesting that if such assays were introduced into blood screening they might totally abrogate the infectious window and prevent blood transmission of HIV. (2) Hepatitis G Virus (HGV)-Hepatitis C Virus (HCV) Interactions. In collaboration with Centers for Disease Control and Prevention, this study will infect HCV carrier chimps with HGV and also simultaneously infect two chimps with HCV and HGV to determine whether HGV facilitates clearance of HCV as suggested in human studies. (3) Fulminant Hepatitis. Using samples from rare cases of fulminant hepatitis C, this study will seek to identify a virulent strain of HCV by chimp inoculation and serial passage. (4) Viral Inactivation. This study will use the chimp model to establish the safety of psoralen/ ultraviolet light-inactivated platelets. This viral inactivation procedure is the first to maintain the integrity of the cellular components of blood. In vitro studies indicate that the method inactivates a broad array of viruses including HIV, hepadnaviruses and flaviviruses, the latter serving as models form hepatitis B virus and HCV. If inactivation is confirmed in vivo, this method should have broad application for platelet and possibly for red blood cell transfusions.
| Alter, Harvey J (2013) The road not taken or how I learned to love the liver: A personal perspective on hepatitis history. Hepatology : |
| Zhang, Pei; Wu, Charles G; Mihalik, Kathleen et al. (2007) Hepatitis C virus epitope-specific neutralizing antibodies in Igs prepared from human plasma. Proc Natl Acad Sci U S A 104:8449-54 |
| Lin, Lily; Hanson, Carl V; Alter, Harvey J et al. (2005) Inactivation of viruses in platelet concentrates by photochemical treatment with amotosalen and long-wavelength ultraviolet light. Transfusion 45:580-90 |
| Thomson, Michael; Nascimbeni, Michelina; Havert, Michael B et al. (2003) The clearance of hepatitis C virus infection in chimpanzees may not necessarily correlate with the appearance of acquired immunity. J Virol 77:862-70 |
