Most of our knowledge of the structure and function of the hepatitis B virus (HBV) genome comes from the analysis of the viral DNA sequences cloned in bacteria1-3. Because the physical state of cloned HBV DNA differs from HBV DNA encapsidated in the virion - for example, it lacks the nick-gap structure4, and a covalently linked protein5 - the question arises as to whether it can initiate HBV replication in vitro 6 or in vivo. We describe here the development of typical acute viral hepatitis, and the detection of HBV-specific DNA sequences in the serum and liver, in a chimpanzee inoculated with cloned HBV DNA. This demonstrates that neither the virion proteins nor the nick-gap structure of the virion DNA are needed for the initiation of replication of HBV in vivo.
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