The precore gene of the woodchuck hepatitis virus genome is not essential for viral replication in the natural host
| Autor: | Michael C. Kew, P. J. Cote, B. C. Tennant, W. E. Hornbuckle, Roger H. Miller, Hong-Shu Chen, John L. Gerin, Robert H. Purcell |
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| Rok vydání: | 1992 |
| Předmět: |
viruses
Molecular Sequence Data Immunology Mutagenesis (molecular biology technique) Hepatitis Animal Hepadnaviridae Virus Replication medicine.disease_cause Microbiology Virus Virology medicine Animals Protein Precursors Gene Hepatitis B virus Base Sequence biology Viral Core Proteins Point mutation Woodchuck hepatitis virus biochemical phenomena metabolism and nutrition biology.organism_classification digestive system diseases Animals Newborn Liver Viral replication Marmota Insect Science Carrier State Mutagenesis Site-Directed Research Article |
| Zdroj: | Journal of Virology. 66:5682-5684 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.66.9.5682-5684.1992 |
| Popis: | A number of naturally occurring hepatitis B virus mutants that cannot synthesize the virus precore protein have been identified. Such mutants have been associated with more severe forms of hepatitis, including fulminant hepatitis. The most common mutation observed is a substitution of G to A in the distal precore gene that converts a codon specifying Trp (TGG) to a termination codon (TAG). Using oligonucleotide-directed mutagenesis, we have produced the same point mutation in the precore gene of an infectious clone of woodchuck hepatitis virus (WHV). Transfection of mutant WHV DNA into the livers of adult woodchucks resulted in replication of the mutant in three of three susceptible animals. Levels of virus replication and transient elevations in liver enzymes in serum were similar to those of adult animals infected with wild-type WHV. Virions, found to possess mutant precore genes by polymerase chain reaction amplification and DNA sequencing, were recovered from the serum of one of the animals and inoculated subcutaneously into neonatal woodchucks. They produced infection in all five animals studied. The level of virus replication in neonatal animals infected with this mutant virus was comparable to that found in neonatal woodchucks infected with wild-type WHV, but none of five woodchucks infected with the precore mutant virus as neonates became chronic virus carriers. It was concluded that the precore gene of the WHV genome is not essential for virus replication in the natural host but may be important for chronic infection. |
| Databáze: | OpenAIRE |
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