Early dynamics of hepatitis B virus in chimeric mice carrying human hepatocytes monoinfected or coinfected with genotype G.
Of the 8 genotypes of HBV (genotypes A-H), genotype G is unique in that it has an insertion in the core gene and two stop codons in the precore region preventing the synthesis of hepatitis B e antigen. Most individuals with genotype G are coinfected with other genotypes, typically genotype A. Mice with severe combined immunodeficiency disease carrying human hepatocytes were infected with HBV particles propagated in Huh7 cells in culture. Mice monoinfected with genotype G did not raise detectable HBV DNA in serum, although products of the core gene emerged 4 to 8 weeks after inoculation. When they were superinfected with genotype A at week 10, however, HBV DNA of genotype A developed, which was replaced almost completely by that of genotype G within 10 weeks. Such a rapid takeover was also observed in mice initially infected with genotype A or C and superinfected with genotype G. Similar viral dynamics occurred in mice simultaneously coinfected with genotypes G and A. Takeover was markedly enhanced in mice inoculated with a serum passage containing genotype G with a trace of genotype A. Coinfection of mice with genotypes G and A induced abundant cellular steatosis along with increased fibrosis in the liver, which was not detected in mice monoinfected with genotype A or G.


CONCLUSIONS
Genotype G can monoinfect chimeric mice at very low levels, and its replication increases maredly when coinfected with other genotypes. Coinfection with genotype G could enhance fibrosis under immunocompromised states.
Sugiyama
Masaya
M
Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Tanaka
Yasuhito
Y
Sakamoto
Tomoyuki
T
Maruyama
Isao
I
Shimada
Takashi
T
Takahashi
Satoru
S
Shirai
Tomoyuki
T
Kato
Hideaki
H
Nagao
Masataka
M
Miyakawa
Yuzo
Y
Mizokami
Masashi
M
D000818:Animals; D002460:Cell Line; D004279:DNA, Viral / Q000097:blood*; D005838:Genotype; D006509:Hepatitis B / Q000473:pathology / Q000821:virology*; D006515:Hepatitis B virus / Q000235:genetics / Q000472:pathogenicity*; D022781:Hepatocytes / Q000637:transplantation / Q000821:virology*; D006801:Humans; D008099:Liver / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D010957:Plasmids; D017422:Sequence Analysis, DNA; D015163:Superinfection / Q000821:virology*; D014162:Transfection; D018183:Transplantation Chimera; D014758:Viral Core Proteins / Q000235:genetics
D004279:DNA, Viral; D014758:Viral Core Proteins