IPNV VP5, a novel anti-apoptosis gene of the Bcl-2 family, regulates Mcl-1 and viral protein expression.
VP5, a 5'-terminal, small open reading frame in segment A of the aquatic birnavirus (infectious pancreatic necrosis virus, IPNV) genome, encodes a 17-kDa nonstructural protein. We previously reported apoptosis induced by IPNV in a fish cell line. In the present study, we cloned and identified VP5 and tested its function. Comparisons of the amino acid sequence of VP5 with well-known Bcl-2 family member proteins showed that the VP5 protein contains Bcl-2 homology (BH) domains BH1, BH2, BH3, and BH4 but without the transmembrane region. VP5-stable clones enhanced viability, prevented membrane blebbing, delayed DNA internucleosomal cleavage, and decreased virus titer during IPNV infection but, when deleted, BH domains 1 and 2 could lose the preventable ability. In addition, VP5 was demonstrated to be able to enhance or assist in maintaining the functional half-life of survival factor Mcl-1 and regulate specific viral protein expression during the early replication cycle. Finally, we found that VP5 was capable of enhancing cell viability when cells were exposed to UV irradiation. In summary, these results suggest that the aquatic birnavirus may utilize a notable strategy via VP5 to regulate the host apoptosis-off system for enhancing progeny production.
Hong
Jiann-Ruey
JR
Laboratory of Marine Molecular Biology and Biotechnology, Institute of Zoology, Academia Sinica, Nankang, Taipei 115, Taiwan, ROC.
Gong
Hong-Yi
HY
Wu
Jen-Leih
JL
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D002213:Capsid / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D036022:Capsid Proteins; D002460:Cell Line; D003001:Cloning, Molecular; D005786:Gene Expression Regulation; D018061:Infectious pancreatic necrosis virus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D008969:Molecular Sequence Data; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012474:Salmon; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
D036022:Capsid Proteins; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014764:Viral Proteins