Hepatitis B spliced protein (HBSP) generated by a spliced hepatitis B virus RNA participates in abnormality of fibrin formation and functions by binding to fibrinogen γ chain.
Hepatitis B spliced protein (HBSP) encoded by a 2.2 kb singly spliced hepatitis B virus (HBV) pre-genomic RNA (spliced between positions 2447 and 489 nt) is involved in the pathogenesis of HBV infection, whereas the exact mechanism is far from being fully elucidated. In this study, a yeast two-hybrid system using HBSP as bait was employed to screen binding partners for HBSP from a human liver cDNA library. The interaction between HBSP and fibrinogen γ chain (FGG) was further confirmed in vitro using a GST pull-down assay and confirmed in vivo using a mammalian two-hybrid assay and co-immunoprecipitation. It was identified that this interaction is mediated by the N terminal 47 amino acid residues of HBSP. HBSP could inhibit fibrin polymerization, factor XIIIa-mediated fibrin cross-linking, adhesion of platelets to fibrinogen and ADP-stimulated platelet aggregation. However, the interaction-mediating fragment 1-47 of HBSP is not sufficient for the inhibitory activity on fibrinogen function. The findings suggested that HBSP may participate in the hemostatic abnormality in patients with HBV-related liver diseases.
Chen
Jin-Yan
JY
Key Laboratory of Tumor Microbiology, Department of Medical Microbiology, Fujian Medical University, Fuzhou 350004, Fujian, PR China.
Chen
Wan-Nan
WN
Liu
Ling-Ling
LL
Lin
Wan-Song
WS
Jiao
Bo-Yan
BY
Wu
Yun-Li
YL
Lin
Jian-Yin
JY
Lin
Xu
X
D000328:Adult; D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D026122:Factor XIIIa / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D015723:Gene Library; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D008099:Liver / Q000378:metabolism; D008969:Molecular Sequence Data; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation / Q000187:drug effects; D012326:RNA Splicing; D020798:Two-Hybrid System Techniques; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology
C478361:HBSP protein, Hepatitis B virus; D014764:Viral Proteins; C027539:fibrinopeptides gamma; D005337:Fibrin; D005340:Fibrinogen; D026122:Factor XIIIa