Superinfection exclusion in duck hepatitis B virus infection is mediated by the large surface antigen.
Superinfection exclusion is the phenomenon whereby a virus prevents the subsequent infection of an already infected host cell. The Pekin duck hepatitis B virus (DHBV) model was used to investigate superinfection exclusion in hepadnavirus infections. Superinfection exclusion was shown to occur both in vivo and in vitro with a genetically marked DHBV, DHBV-ClaI, which was unable to establish an infection in either DHBV-infected ducklings or DHBV-infected primary duck hepatocytes (PDHs). In addition, exclusion occurred in vivo even when the second virus had a replicative advantage. Superinfection exclusion appears to be restricted to DHBV, as adenovirus, herpes simplex virus type 1, and vesicular stomatitis virus were all capable of efficiently infecting DHBV-infected PDHs. Exclusion was dependent on gene expression by the original infecting virus, since UV-irradiated DHBV was unable to mediate the exclusion of DHBV-ClaI. Using recombinant adenoviruses expressing DHBV proteins, we determined that the large surface antigen mediated exclusion. The large surface antigen is known to cause down-regulation of a DHBV receptor, carboxypeptidase D (CPD). Receptor down-regulation is a mechanism of superinfection exclusion seen in other viral infections, and so it was investigated as a possible mechanism of DHBV-mediated exclusion. However, a mutant large surface antigen which did not down-regulate CPD was still capable of inhibiting DHBV infection of PDHs. In addition, exclusion of DHBV-ClaI did not correlate with a decrease in CPD levels. Finally, virus binding assays and confocal microscopy analysis of infected PDHs indicated that the block in infection occurs after internalization of the second virus. We suggest that superinfection exclusion may result from the role of the L surface antigen as a regulator of intracellular trafficking.
Walters
Kathie-Anne
KA
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada.
Joyce
Michael A
MA
Addison
William R
WR
Fischer
Karl P
KP
Tyrrell
D Lorne J
DL
D000818:Animals; D002268:Carboxypeptidases / Q000502:physiology; D024882:Drug Resistance, Viral; D004372:Ducks; D018347:Hepadnaviridae Infections / Q000209:etiology*; D006514:Hepatitis B Surface Antigens / Q000502:physiology*; D015611:Hepatitis B Virus, Duck / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D022781:Hepatocytes / Q000821:virology; D019259:Lamivudine / Q000494:pharmacology; D014779:Virus Replication
D006514:Hepatitis B Surface Antigens; D019259:Lamivudine; D002268:Carboxypeptidases; C078874:carboxypeptidase D