Nuclear covalently closed circular viral genomic DNA in the liver of hepatocyte nuclear factor 1 alpha-null hepatitis B virus transgenic mice

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.