Inhibition of influenza A virus reproduction by a ribozyme targeted against PB1 mRNA.
A ribozyme gene directed at a specific cleavage of mRNA coding for PB1 protein, a component of RNA-dependent RNA-polymerase of influenza A virus, was constructed. The avian adenovirus CELO virus-associated RNA (VA RNA CELO) promoter and human cytomegalovirus (CMV) promoter were used for the permanent expression of the ribozyme in cell lines. The cells were infected with influenza A virus strains A/Singapore/1/57 and A/WSN/33, and the suppression of the virus reproduction and virus-specific protein synthesis was measured. The maximal level of the inhibition of virus reproduction as compared to the reproduction in non-transformed cells was 93.5%. Defective recombinant adenoviruses were constructed carrying the genes of functional and non-functional ribozymes under the control of human cytomegalovirus (CMV) promoter. The reproduction of A/WSN/33 virus in CV-1 cells preinfected with recombinant adenoviruses was shown to be suppressed.
Lazarev
V N
VN
Institute of Agricultural Biotechnology, Russian Academy of Agricultural Science, Moscow.
Shmarov
M M
MM
Zakhartchouk
A N
AN
Yurov
G K
GK
Misurina
O U
OU
Akopian
T A
TA
Grinenko
N F
NF
Grodnitskaya
N G
NG
Kaverin
N V
NV
Naroditsky
B S
BS
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003587:Cytomegalovirus / Q000235:genetics; D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D010957:Plasmids; D011401:Promoter Regions, Genetic; D016337:RNA, Catalytic / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics*; D014779:Virus Replication / Q000502:physiology
D016337:RNA, Catalytic; D012333:RNA, Messenger; D012367:RNA, Viral; D014764:Viral Proteins; C077346:influenza virus polymerase basic protein 1; D012324:RNA-Dependent RNA Polymerase