[HEV capsid protein interacts with CYP 2A6 and decreases its coumarin 7-hydroxylation activity].
E2 is a recombinant hepatitis E virus capsid protein including its main antigenic determinants but lacking of the particle assembling domain. P239 was the C-terminal extending protein of E2 and could self-assemble to form virus like particles, which might serve as mimicry of virions both structurally and antigenically. We previously used yeast two-hybrid system to screen proteins interacting with E2 based on a human hepatocyte cDNA library. One candidate was identified as the segment (aa388-437) of cytochrome P450 2A6 protein, which is predominantly expressed in liver and important for metabolization. Some studies have demonstrated that hepatitis virus infection may altered cell metabolic clearance of coumrarin which were rapidly matebolised by CYP2A6. In this research, we demonstrated that the protein interaction between HEV capsid proteins and CYP2A6 by pull-down and co-immunoprecipitation. It was also found that their interaction could decrease the CYP2A6 catalytic activity when p239 was incubated within the CYP2A6-transfected Huh7 cells. These results suggested that CYP2A6 might be related to the pathological process when HEV invaded host cells.
Tang
Ming
M
National Institute of Diagnostics and Vaccine Development in Infectious Diseases, Xiamen University, Xiamen, 361005. tangming@xmu.edu.cn
Zheng
Zi-zheng
ZZ
Sun
Yuan-yuan
YY
He
Shui-zhen
SZ
Zhao
Min
M
Huang
Hui
H
Miao
Ji
J
Zhang
Jun
J
Xia
Ning-shao
NS
D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism*; D036022:Capsid Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D003374:Coumarins / Q000378:metabolism; D065637:Cytochrome P-450 CYP2A6; D016752:Hepatitis E virus / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000378:metabolism; D047468:Immunoprecipitation; D011485:Protein Binding; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D036022:Capsid Proteins; D003374:Coumarins; D007093:Imidazoles; D011994:Recombinant Proteins; C517283:coumarin 7; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6