Studies Of Viral Hepatitis And Aids In The Chimpanzee Model

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Abstract

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. Other studies we have performed in this model include the following: 1) We have 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 suggested that molecular assays for HIV that were introduced into blood screening might totally abrogate the infectious window and prevent blood transmission of HIV. Similar studies were 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 sensitive nucleic acid testing assays currently available for blood screening; 2)the duration (window) during which blood can transmit HCV in the absence of viral markers appears to less than two weeks prior to the time when the virus rapidly grows (ramps-up) in the recipient. Thus, there is a risk period, but it is brief. 3) chimpanzees infected with these low dose inocula tend to have a short course of viremia and then fully recover; however, they remain susceptible to reinfection with HCV. 4)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. 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. Although many additional studies could be performed in chimpanzeee, NIH has prohibited further use of this model. Thus no active chimpanzee studies are in progress, but we maintain the protocol so as to allow further analysis of stored samples.