Molecular clones of genetically distinct hepatitis B virus genotypes reveal distinct host and drug treatment responses.
Cafiero, Thomas R
Gertje, Hans P
Crossland, Nicholas A
Schwartz, Robert E
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AbstractPatient-derived HBV infectious clones replicated robustly both in vitro and in vivo. GTs A and D induce more pronounced intrahepatic and proinflammatory cytokine responses which correlated with faster viral clearance. Notably, all 5 HBV clones robustly produced viral particles following transfection into HepG2 cells, and these particles were infectious in HepG2-NTCP cells, primary human hepatocytes and human chimeric mice. Notably, GT D virus exhibited higher infectivity than GTs A, B, C and E in vitro, although it was comparable to GT A and B in the human liver chimeric mice in vivo. HBV capsid inhibitors were more readily capable of suppressing HBV GTs A, B, D and E than C.
Rights/Terms© 2022 The Authors.
KeywordAAV, adeno-associated virus
ALT, alanine aminotransferase
BCP, basic core promoter
CHB, chronic hepatitis B
CpAM, core protein allosteric modulators
DR, direct repeat
HBV, hepatitis B virus
HBVcc, cell culture-derived HBV
HCC, hepatocellular carcinoma
HDI, hydrodynamic injection
MOI, multiplicity of infection
NA, nucleos(t)ide analogue
PHH, primiary human hepatocyte
SVR, sustained virologic response
cccDNA, covalently closed circular DNA
dpi, days post infection
hepatitis B virus
pgRNA, pre-genomic RNA
Identifier to cite or link to this itemhttp://hdl.handle.net/10713/19649
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