Primary human hepatocytes are susceptible to infection by hepatitis delta virus assembled with envelope proteins of woodchuck hepatitis virus.
Hepatitis B virus (HBV) and hepatitis delta virus (HDV) share the HBV envelope proteins. When woodchucks chronically infected with woodchuck hepatitis virus (WHV) are superinfected with HDV, they produce HDV with a WHV envelope, wHDV. Several lines of evidence are provided that wHDV infects not only cultured primary woodchuck hepatocytes (PWH) but also primary human hepatocytes (PHH). Surprisingly, HBV-enveloped HDV (hHDV) and wHDV infected PHH with comparable efficiencies; however, hHDV did not infect PWH. The basis for these host range specificities was investigated using as inhibitors peptides bearing species-specific pre-S (where S is the small envelope protein) sequences. It was found that pre-S1 contributed to the ability of wHDV to infect both PHH and PWH. In addition, the inability of hHDV to infect PWH was not overcome using a chimeric form of hHDV containing WHV S protein, again supporting the essential role of pre-S1 in infection of target cells. One interpretation of these data is that host range specificity of HDV is determined entirely by pre-S1 and that the WHV and HBV pre-S1 proteins recognize different receptors on PHH.
Gudima
Severin
S
Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111-2497, USA.
He
Yiping
Y
Chai
Ning
N
Bruss
Volker
V
Urban
Stephan
S
Mason
William
W
Taylor
John
J
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D017919:Hepatitis B Virus, Woodchuck / Q000235:genetics*; D003698:Hepatitis Delta Virus / Q000235:genetics / Q000254:growth & development*; D022781:Hepatocytes / Q000821:virology*; D006801:Humans; D008392:Marmota; D008958:Models, Molecular; D016415:Sequence Alignment; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism*; D019065:Virus Assembly
D014759:Viral Envelope Proteins