Coinfection study of precore mutant and wild‐type hepatitis B‐like virus in ducklings

The precore mutant hepatitis B virus often emerges from a mixed infection with combined wild‐type and precore mutant viruses. Nevertheless, the precore mutant does not seem to be an evolutionarily favored strain. To investigate the interaction between wildtype and precore mutant hepadnaviruses in an animal model of perinatal transmission, we used an e antigendefective mutant duck hepatitis B virus with mutations inside the stem‐loop structure of precore messenger RNA for this coinfection study. Thirty 1‐day‐old ducklings were infected with wild‐type duck hepatitis B virus, precore mutant virus or both viruses. The amounts of viremia and the distribution of viruses were analyzed by spot hybridization, polymerase chain reaction, restriction fragment length polymorphism, cloning and sequencing. We found that all the ducklings became chronic carriers of duck hepatitis B virus. The precore mutant replicate was less active than wild‐type duck hepatitis B virus, and it could be overgrown by wild‐type virus during the course of coinfection. These results demonstrated that wild‐type duck hepatitis B virus might become the predominant species in a situation similar to the perinatal cotransmission in human beings. This might at least in part explain why the prototype virus could prevail for years. (Hepatology 1994;19:569–576).

[1]  H. Hsu,et al.  Cellular Immune Response to HBcAg in Mother‐to‐Infant Transmission of Hepatitis B Virus , 1992, Hepatology.

[2]  H. Thomas,et al.  Genetic variation in hepatitis B virus. , 1992, Gastroenterology.

[3]  O. Yokosuka,et al.  Variations in codons 84-101 in the core nucleotide sequence correlate with hepatocellular injury in chronic hepatitis B virus infection. , 1992, The Journal of clinical investigation.

[4]  C. Marshall,et al.  Multiple K-ras codon 12 mutations in cholangiocarcinomas demonstrated with a sensitive polymerase chain reaction technique. , 1991, Cancer research.

[5]  O. Yokosuka,et al.  Mutations in the precore region of hepatitis B virus DNA in patients with fulminant and severe hepatitis. , 1991, The New England journal of medicine.

[6]  H. Will,et al.  Mechanism, kinetics, and role of duck hepatitis B virus e-antigen expression in vivo. , 1991, Virology.

[7]  H. Will,et al.  Wild-type and e antigen-minus hepatitis B viruses and course of chronic hepatitis. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[8]  M. Kann,et al.  Identification of a binding site in the hepatitis B virus RNA pregenome for the viral Pol gene product. , 1991, Virology.

[9]  K. Takase,et al.  Fulminant hepatitis B: induction by hepatitis B virus mutants defective in the precore region and incapable of encoding e antigen. , 1991, Gastroenterology.

[10]  H. Will,et al.  Hepatitis B virus unable to secrete e antigen. , 1991, Gastroenterology.

[11]  P. Sarnow,et al.  An RNA hairpin at the extreme 5' end of the poliovirus RNA genome modulates viral translation in human cells , 1991, Journal of virology.

[12]  M. Brunetto,et al.  'e' antigen defective hepatitis B virus and course of chronic infection. , 1991, Journal of hepatology.

[13]  O. Yokosuka,et al.  Detection and direct sequencing of hepatitis B virus genome by DNA amplification method. , 1991, Gastroenterology.

[14]  H. Hsu,et al.  Changes of serum hepatitis B virus DNA and aminotransferase levels during the course of chronic hepatitis B virus infection in children , 1990, Hepatology.

[15]  R. Bartenschlager,et al.  A short cis‐acting sequence is required for hepatitis B virus pregenome encapsidation and sufficient for packaging of foreign RNA. , 1990, The EMBO journal.

[16]  J. Price,et al.  Is a function of the secreted hepatitis B e antigen to induce immunologic tolerance in utero? , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[17]  F Tsuda,et al.  Hepatitis B viruses with precore region defects prevail in persistently infected hosts along with seroconversion to the antibody against e antigen , 1990, Journal of virology.

[18]  M. Omata,et al.  Analysis of ras gene mutations in human hepatic malignant tumors by polymerase chain reaction and direct sequencing. , 1990, Cancer research.

[19]  O. Yokosuka,et al.  Extrahepatic replication of duck hepatitis b virus: More than expected , 1990, Hepatology.

[20]  H. Thomas,et al.  MUTATION PREVENTING FORMATION OF HEPATITIS B e ANTIGEN IN PATIENTS WITH CHRONIC HEPATITIS B INFECTION , 1989, The Lancet.

[21]  O. Yokosuka,et al.  Functional analysis of the pre-C region of DHBV DNA: A transfection study of the pre-C frameshift-mutated DNA. , 1989 .

[22]  J. Main,et al.  Virus-Host Interaction in Chronic Hepatitis B Virus Infection , 1988, Seminars in liver disease.

[23]  H. Sakugawa,et al.  Typing hepatitis B virus by homology in nucleotide sequence: comparison of surface antigen subtypes. , 1988, The Journal of general virology.

[24]  H. Schlicht,et al.  The duck hepatitis B virus pre-C region encodes a signal sequence which is essential for synthesis and secretion of processed core proteins but not for virus formation , 1987, Journal of virology.

[25]  H. Varmus,et al.  Expression of the precore region of an avian hepatitis B virus is not required for viral replication , 1987, Journal of virology.

[26]  K. Okuda Is fulminant B hepatitis more common among infants born to e antigen‐negative carrier mothers? , 1987 .

[27]  H. Hsu,et al.  Fulminant hepatitis in children in Taiwan: the important role of hepatitis B virus. , 1987, The Journal of pediatrics.

[28]  F. Callea,et al.  Chronic hepatitis in HBsAg carriers with serum HBV-DNA and anti-HBe. , 1986, Gastroenterology.

[29]  K. Mullis,et al.  Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia. , 1985, Science.

[30]  A. Dejean,et al.  The hepatitis B virus , 1985, Nature.

[31]  R. Sprengel,et al.  Cloned duck hepatitis B virus DNA is infectious in Pekin ducks , 1984, Journal of virology.

[32]  H. Varmus,et al.  The cloned genome of ground squirrel hepatitis virus is infectious in the animal. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[33]  O. Yokosuka,et al.  Transmission of Duck Hepatitis B Virus from Chinese Carrier Ducks to Japanese Ducklings: A Study of Viral DNA in Serum and Tissue , 1984, Hepatology.

[34]  F. Galibert,et al.  Nucleotide sequence of a cloned duck hepatitis B virus genome: comparison with woodchuck and human hepatitis B virus sequences , 1984, Journal of virology.

[35]  J. Summers,et al.  Experimental transmission of duck hepatitis B virus. , 1983, Virology.

[36]  H. Will,et al.  Cloned HBV DNA causes hepatitis in chimpanzees , 1982, Nature.

[37]  Walter Gilbert,et al.  Hepatitis B virus genes and their expression in E. coli , 1979, Nature.

[38]  B. Schwartz Letter: Ondine's curse. , 1976, Lancet.