Modulation of hepatitis B virus replication by expression of polymerase-surface fusion protein through splicing: implications for viral persistence.
In hepatitis B virus (HBV)-infected livers and -transfected hepatoma cells, spliced transcripts are not essential for HBV replication. However, their ability to modulate HBV replication has not been clearly elucidated. In the current study, we found that the polymerase-surface (PS) fusion protein, generated from a spliced HBV transcript, colocalized with the nuclear pore complex, vimentin, microtubules, and the endoplasmic reticulum (ER) in the perinuclear region of transfected cells. We found that PLC/PRF/5-hepatoma cells expressed PS transcript and PS protein. Hepatitis B surface antigen (HBs) secretion, core particle formation, and HBV DNA synthesis were inhibited by the expression of PS transcript and PS protein, and by expression of PS transcript alone, suggesting that HBV replication is modulated by splicing. Our results suggest that splicing may be one of the outcomes of the host-virus interaction.
Department of Microbiology, Ajou University School of Medicine, Woncheon-dong 5, Suwon 443-721, South Korea.
Gil-Soon
GS
Park
Hee-Young
HY
Kim
Hyun-Soo
HS
Shin
Sun
S
Park
Ho-Joon
HJ
Shin
Kyongmin
K
Kim
D002460:Cell Line; D003593:Cytoplasm / Q000737:chemistry; D004721:Endoplasmic Reticulum / Q000737:chemistry; D015684:Gene Products, pol / Q000096:biosynthesis*; D006514:Hepatitis B Surface Antigens / Q000096:biosynthesis*; D006515:Hepatitis B virus / Q000502:physiology*; D022781:Hepatocytes / Q000737:chemistry / Q000821:virology; D006801:Humans; D008870:Microtubules / Q000737:chemistry; D012326:RNA Splicing; D014746:Vimentin / Q000378:metabolism; D014760:Viral Fusion Proteins / Q000096:biosynthesis*; D019065:Virus Assembly; D014779:Virus Replication
D015684:Gene Products, pol; D006514:Hepatitis B Surface Antigens; C066027:P protein, Hepatitis B virus; D014746:Vimentin; D014760:Viral Fusion Proteins