Ak. Raney et al., Nuclear covalently closed circular viral genomic DNA in the liver of hepatocyte nuclear factor 1 alpha-null hepatitis B virus transgenic mice, J VIROLOGY, 75(6), 2001, pp. 2900-2911
The role of hepatocyte nuclear factor lot (HNF1 alpha) in the regulation of
hepatitis B virus (HBV) transcription and replication in vivo was investig
ated using a HNF1 alpha -null HBV transgenic mouse model. HBV transcription
was not measurably affected by the absence of the HNF1 alpha transcription
factor. However, intracellular viral replication intermediates were increa
sed two- to fourfold in mice lacking functional HNF1 alpha protein. The inc
rease in encapsidated cytoplasmic replication intermediates in HNF1-null HB
V transgenic mice was associated with the appearance of nonencapsidated nuc
lear covalently closed circular (CCC) viral genomic DNA. Viral CCC DNA was
not readily detected in HNF1 alpha -expressing HEV transgenic mice. This in
dicates the synthesis of nuclear HBV CCC DNA, the proposed viral transcript
ional template found in natural infection, is regulated either by subtle al
terations in the levels of viral transcripts or by changes in the physiolog
ical state of the hepatocyte in this in vivo model of HBV replication.