Influenza virus genome C4 promoter/origin attenuates its transcription and replication activity by the low polymerase recognition activity.
A natural variation is observed at position 4 of the 3'-end of influenza A virus genomes, where U (U4) or C (C4) is present. The replicon activity of C4 was 28% of U4. We compared the transcription and replication activity of U4 [v84(U4)], C4 [v84(C4)] and the complimentary RNA (c84) using the purified influenza virus RNA polymerase in vitro. ApG-primed replication activities of v84(C4) and c84 were 23.8% and 7.8% of v84(U4). Globin mRNA-primed transcription activities of v84(C4) and c84 were 36.9% and 6.81% of v84(U4). De novo replication activities of v84(C4) and c84 were 21.3 and 10.2% of v84(U4). This difference came from their polymerase binding activity. When all the eight genome segments of WSN strain were changed to U4, the virus titer was 760 times higher than the wild type. However, its pathogenicity in mice was lower than the wild type.
Unit of Viral Genome Regulation, Institut Pasteur of Shanghai, Key Laboratory of Molecular Virology & Immunology, Chinese Academy of Sciences, 411 Hefei Road,Shanghai 200025, PR China
Hongbing
H
Jiang
Shijian
S
Zhang
Qiang
Q
Wang
Jinlan
J
Wang
Liqing
L
Geng
Tetsuya
T
Toyoda
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D004285:Dogs; D005260:Female; D015870:Gene Expression; D014644:Genetic Variation; D016679:Genome, Viral; D006801:Humans; D009980:Influenza A virus / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology*; D016899:Interferon-beta / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D012093:Replicon; D014158:Transcription, Genetic; D017361:Viral Nonstructural Proteins / Q000235:genetics; D014774:Virulence / Q000235:genetics / Q000502:physiology; D014779:Virus Replication / Q000235:genetics* / Q000502:physiology*
C085820:INS1 protein, influenza virus; D012333:RNA, Messenger; D012367:RNA, Viral; D017361:Viral Nonstructural Proteins; D016899:Interferon-beta; D012321:DNA-Directed RNA Polymerases