Complete nucleotide sequence of a molecular clone of woodchuck hepatitis virus that is infectious in the natural host

Woodchuck hepatitis virus (WHV) DNA was cloned from viral particles obtained from the serum of a woodchuck with a naturally acquired infection. The complete nucleotide sequence of the virus genome was determined and found to be 3323 base pairs long. Transfection experiments demonstrated that the recombinant WHV DNA was infectious in each of 18 woodchucks tested and established a chronic carrier state in 1 of 13 neonates and 3 of 5 adult animals. WHV DNA from serum particles from the chronically infected neonate was cloned and the nucleotide sequence of three independent recombinants was compared directly with that of the input recombinant DNA. The consensus sequence of the three progeny genomes was identical to that of the parental DNA sequence. Therefore, transfection of woodchuck livers with recombinant WHV DNA induces active virus replication and gene expression and yields progeny genomes that are faithful copies of the input virus genome.