Polymerase complex with lysine at position 627 of the PB2 of influenza virus A/Hong Kong/483/97 (H5N1) efficiently transcribes and replicates virus genes in mouse cells.
Influenza virus A/Hong Kong/483/97 (H5N1) (HK483-K) has the PB2 with lysine at position 627 (PB2-627K) and is highly pathogenic in chickens and mice. On the other hand, the pathogenicity of mutant virus (HK483-E), which was generated by substituting lysine with glutamic acid at the position of the PB2, is lower than that of HK483-K in mice, but is highly pathogenic in chickens. The PB2 is one of the components of heterotrimeric polymerase complex, which plays roles in the transcription and replication of virus genes. Cell-free polymerase assay revealed that intrinsic transcription activity of the polymerase complex with PB2-627K is higher than that of glutamic acid (PB2-627E). In chicken cells, transcription efficiency of the polymerase complex with PB2-627E was not lower than those with PB2-627K, indicating that transcription of virus genes is modulated by some host factors in chicken cells, resulting in high growth. Polymerase complex with PB2-627K efficiently transcribes and replicates virus polymerase genes in mouse cells, leading to high growth of HK483-K compared with that of HK483-E. The results of our experiments clearly suggest that efficient transcription and replication of virus genes by polymerase complex result in the higher pathogenicity in mice.
Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Kita 18, Nishi 9, Kita-ku, Sapporo 060-0818, Japan.
Naoki
N
Yamamoto
Yoshihiro
Y
Sakoda
Masatoshi
M
Okamatsu
Hiroshi
H
Kida
D019943:Amino Acid Substitution; D000818:Animals; D002460:Cell Line; D002645:Chickens; D005260:Female; D053124:Influenza A Virus, H5N1 Subtype / Q000201:enzymology* / Q000235:genetics / Q000502:physiology*; D008239:Lysine / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
C502893:PB2 protein, influenza virus; D014764:Viral Proteins; D008239:Lysine
H5N1; Influenza A virus; PB2; Polymerase