Large isoform of hepatitis delta antigen activates serum response factor-associated transcription.

Abstract	Hepatitis delta virus infection sometimes causes severe and fulminant hepatitis as a coinfection or superinfection along with the hepatitis B virus. To elucidate the underlying mechanism of injury caused by hepatitis delta virus, we examined whether two isoforms of the hepatitis delta antigen (HDAg) had any effect on five well defined intracellular signal transduction pathways: serum response factor (SRF)-, serum response element (SRE)-, nuclear factor kappaB-, activator protein 1-, and cyclic AMP response element-dependent pathways. Reporter assays revealed that large HDAg (LHDAg) activated the SRF- and SRE-dependent pathways. In contrast, small HDAg (SHDAg) did not activate any of five pathways. LHDAg enhanced the transcriptional ability of SRF without changing its DNA binding affinity in an electrophoretic mobility shift assay. In addition, LHDAg activated a rat SM22alpha promoter containing SRF binding site and a human c-fos promoter containing SRE. In conclusion, LHDAg, but not SHDAg, enhances SRF-associated transcriptions. Despite structural similarities between the two HDAgs, there are significant differences in their effects on intracellular signal transduction pathways. These results may provide clues that will aid in the clarification of functional differences between LHDAg and SHDAg and the pathogenesis of delta hepatitis.
Authors	T Goto, N Kato, S K Ono-Nita, H Yoshida, M Otsuka, Y Shiratori, M Omata
Journal	The Journal of biological chemistry (J Biol Chem) Vol. 275 Issue 48 Pg. 37311-6 (Dec 01 2000) ISSN: 0021-9258 [Print] United States
PMID	10961986 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antigens, Viral DNA Primers DNA-Binding Proteins Microfilament Proteins Muscle Proteins Nuclear Proteins Protein Isoforms Serum Response Factor Tagln protein, mouse transgelin
Topics	Animals Antigens, Viral (physiology) Base Sequence DNA Primers DNA-Binding Proteins (physiology) Hepatitis Delta Virus (immunology) Microfilament Proteins (genetics) Muscle Proteins (genetics) Mutagenesis, Site-Directed Nuclear Proteins (physiology) Promoter Regions, Genetic Protein Isoforms (physiology) Rats Serum Response Factor Signal Transduction Transcription, Genetic (physiology)

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