title: PB2 segment promotes high-pathogenicity of H5N1 avian influenza viruses in mice.
abstract: H5N1 influenza viruses with high lethality are a continuing threat to humans and poultry. Recently, H5N1 high-pathogenicity avian influenza virus (HPAIV) has been shown to transmit through aerosols between ferrets in lab experiments by acquiring some mutation. This is another deeply aggravated threat of H5N1 HPAIV to humans. To further explore the molecular determinant of H5N1 HPAIV virulence in a mammalian model, we compared the virulence of A/Duck/Guangdong/212/2004 (DK212) and A/Quail/Guangdong/90/2004 (QL90). Though they were genetically similar, they had different pathogenicity in mice, as well as their 16 reassortants. The results indicated that a swap of the PB2 gene could dramatically decrease the virulence of rgDK212 in mice (1896-fold) but increase the virulence of rgQL90 in mice (60-fold). Furthermore, the polymerase activity assays showed that swapping PB2 genes between these two viruses significantly changed the activity of polymerase complexes in 293T cells. The mutation Ser715Asn in PB2 sharply attenuated the virulence of rgDK212 in mice (2710-fold). PB2 segment promotes high-pathogenicity of H5N1 avian influenza viruses in mice and 715 Ser in PB2 plays an important role in determining high virulence of DK212 in mice.
authors.affiliation: College of Veterinary Medicine, South China Agricultural University Guangzhou, China.
authors.forename: Hailiang
authors.initials: H
authors.lastname: Sun
authors.affiliation: College of Veterinary Medicine, South China Agricultural University Guangzhou, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Cui
authors.affiliation: College of Veterinary Medicine, South China Agricultural University Guangzhou, China.
authors.forename: Yafen
authors.initials: Y
authors.lastname: Song
authors.affiliation: College of Veterinary Medicine, South China Agricultural University Guangzhou, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Qi
authors.affiliation: College of Veterinary Medicine, South China Agricultural University Guangzhou, China.
authors.forename: Xiaokang
authors.initials: X
authors.lastname: Li
authors.affiliation: College of Veterinary Medicine, South China Agricultural University Guangzhou, China.
authors.forename: Wenbao
authors.initials: W
authors.lastname: Qi
authors.affiliation: College of Veterinary Medicine, South China Agricultural University Guangzhou, China.
authors.forename: Chenggang
authors.initials: C
authors.lastname: Xu
authors.affiliation: College of Veterinary Medicine, South China Agricultural University Guangzhou, China.
authors.forename: Peirong
authors.initials: P
authors.lastname: Jiao
authors.affiliation: College of Veterinary Medicine, South China Agricultural University Guangzhou, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Liao
keywords: H5N1; influenza virus; mice; mutants; reassortant; virulence