This laboratory in collaboration with the Southwest Foundation for Biomedical Research in San Antonio, TX has performed a series of studies in the chimpanzee model including the initial transmission of the non-A, non-B hepatitis agent that subsequently proved to be the hepatitis C virus.Current studies in this model include the following: 1) We have previousy used the chimp model to define the early events of HIV infection and had evidence from serial transmission studies that blood did not transmit HIV during the incubation period of the infection prior to the first detection of HIV RNA. This suggests that molecular assays for HIV that 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. In contrast to the HIV experiment, we have found that HCV can be transmitted by blood that has undetectable levels of HCV RNA by the most sentive nucleieic acid testing assays currently available for blood screening; 2)Viral 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.
| 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 |
