Woodchuck hepatitis virus X protein is required for viral infection in vivo.
The X gene of the mammalian hepadnaviruses is believed to encode a protein of 17 kDa which has been shown to transactivate a wide range of viral and cellular promoters. The necessity for X gene expression during the viral life cycle in vivo has recently been suggested (H.-S. Chen, S. Kaneko, R. Girones, R. W. Anderson, W. E. Hornbuckle, B. C. Tennant, P. J. Cote, J. L. Gerin, R. H. Purcell, and R. H. Miller, J. Virol. 67:1218-1226, 1993). We have independently constructed two variants of woodchuck hepatitis virus (WHV) with mutations in the X coding region. Transient transfection of two different hepatoma cell lines showed that these WHV X gene mutants were competent for virus replication in vitro. To determine whether X expression was required for viral replication in vivo, we injected mutant and wild-type genomes into the livers of susceptible woodchucks. While the wild-type WHV genomes were infectious in all animals examined, the mutant genomes did not initiate a WHV infection in woodchucks. These results indicate that the X gene of the hepadnaviruses plays a major role in viral replication in vivo.
Zoulim
F
F
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
Saputelli
J
J
Seeger
C
C
D000818:Animals; D005455:Fluorescent Antibody Technique; D006509:Hepatitis B / Q000235:genetics*; D006510:Hepatitis B Antibodies / Q000097:blood; D006512:Hepatitis B Core Antigens / Q000302:isolation & purification; D017919:Hepatitis B Virus, Woodchuck / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity*; D008099:Liver / Q000382:microbiology; D008392:Marmota; D009154:Mutation; D015534:Trans-Activators / Q000235:genetics*; D054334:Viral Regulatory and Accessory Proteins; D014779:Virus Replication / Q000235:genetics
D006510:Hepatitis B Antibodies; D006512:Hepatitis B Core Antigens; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein