Hepatitis A virus (HAV) proteinase 3C inhibits HAV IRES-dependent translation and cleaves the polypyrimidine tract-binding protein.
Hepatitis A virus (HAV) infection is still an important issue worldwide. A distinct set of viruses encode proteins that enhance viral cap-independent translation initiation driven by an internal ribosome entry site (IRES) and suppress cap-dependent host translation. Unlike cytolytic picornaviruses, replication of HAV does not cause host cell shut off, and it has been questioned whether HAV proteins interfere with its own and/or host translation. HAV proteins were coexpressed in Huh-7 cells with reporter genes whose translation was initiated by either cap-dependent or cap-independent mechanisms. Among the proteins tested, HAV proteinase 3C suppressed viral IRES-dependent translation. Furthermore, 3C cleaved the polypyrimidine tract-binding protein (PTB) whose interaction with the HAV IRES had been demonstrated previously. The combined results suggest that 3C-mediated cleavage of PTB might be involved in down-regulation of viral translation to give way to subsequent viral genome replication.
Kanda
T
T
Department of Medicine and Clinical Oncology, Graduate School of Medicine, Chiba University, Inohana, Chuo-ku, Chiba, Japan. kandat-cib@umin.ac.jp
Gauss-Müller
V
V
Cordes
S
S
Tamura
R
R
Okitsu
K
K
Shuang
W
W
Nakamoto
S
S
Fujiwara
K
K
Imazeki
F
F
Yokosuka
O
O
D000086042:3C Viral Proteases; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D017930:Genes, Reporter; D030041:Hepatitis A virus / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D038941:Polypyrimidine Tract-Binding Protein / Q000378:metabolism*; D014176:Protein Biosynthesis; D014764:Viral Proteins / Q000378:metabolism*; D014779:Virus Replication
D014764:Viral Proteins; D038941:Polypyrimidine Tract-Binding Protein; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases