PB2 Protein of a Highly Pathogenic Avian Influenza Virus Strain A/chicken/Yamaguchi/7/2004 (H5N1) Determines Its Replication Potential in Pigs

Manzoor, Rashid; Sakoda, Yoshihiro; Nomura, Naoki; Tsuda, Yuichi; Ozaki, Hiroichi; Okamatsu, Masatoshi; Kida, Hiroshi

doi:10.1128/jvi.01879-08

Cited by 70 publications

(54 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Still, virus containing the SR polymorphism yielded approximately10-fold more infectious progeny than WT virus. This intermediate level of restriction in porcine cells is consistent with only a moderate level of restriction observed in pigs infected with single-gene reassortant viruses containing either avian or swine PB2 (17). By contrast, similar yields were observed for all viruses from parallel infections performed in chicken DF1 cells (Fig.…”

Section: Sr Polymorphism Enhances Virus Replicationsupporting

confidence: 63%

“…PB2 K627 correlates with enhanced polymerase activity, virus replication, transmission, and in certain cases, pathogenicity and mortality in mammals (5,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). PB2 K627 also correlates with moderately enhanced influenza virus replication in pigs, consistent with pigs serving as an intermediary viral reservoir between birds and humans (17). Conversely, the presence of a glutamic acid at this position severely attenuates replication efficiency and pathogenicity in mammalian systems (7,9).…”

mentioning

confidence: 67%

See 1 more Smart Citation

Adaptive strategies of the influenza virus polymerase for replication in humans

Mehle¹,

Doudna

2009

Proc. Natl. Acad. Sci. U.S.A.

342

373

View full text Add to dashboard Cite

Transmission of influenza viruses into the human population requires surmounting barriers to cross-species infection. Changes in the influenza polymerase overcome one such barrier. Viruses isolated from birds generally contain polymerases with the aviansignature glutamic acid at amino acid 627 in the PB2 subunit. These polymerases display restricted activity in human cells. An adaptive change in this residue from glutamic acid to the human-signature lysine confers high levels of polymerase activity in human cells. This mutation permits escape from a species-specific restriction factor that targets polymerases from avian viruses. A 2009 swineorigin H1N1 influenza A virus recently established a pandemic infection in humans, even though the virus encodes a PB2 with the restrictive glutamic acid at amino acid 627. We show here that the 2009 H1N1 virus has acquired second-site suppressor mutations in its PB2 polymerase subunit that convey enhanced polymerase activity in human cells. Introduction of this polymorphism into the PB2 subunit of a primary avian isolate also increased polymerase activity and viral replication in human and porcine cells. An alternate adaptive strategy has also been identified, whereby introduction of a human PA subunit into an avian polymerase overcomes restriction in human cells. These data reveal a strategy used by the 2009 H1N1 influenza A virus and identify other pathways by which avian and swine-origin viruses may evolve to enhance replication, and potentially pathogenesis, in humans.2009 A(H1N1) ͉ PB2 ͉ species barriers

show abstract

Section: Sr Polymorphism Enhances Virus Replicationsupporting

confidence: 63%

mentioning

confidence: 67%

Adaptive strategies of the influenza virus polymerase for replication in humans

Mehle¹,

Doudna

2009

Proc. Natl. Acad. Sci. U.S.A.

342

373

View full text Add to dashboard Cite

show abstract

“…There is increasing evidence that the viral polymerases play a major role in host adaptation (10). More recently, Manzoor et al have demonstrated that a swine-derived PB2 gene conferred enhanced replicative potential to the reassortant virus that possessed seven genes of avian origin (33). It also should be noted that several researchers have proposed the NP gene as a determinant of host range that can either restrict or attenuate virus replication (44,48,54), thereby controlling the successful transmission of virus to a new host (2).…”

Section: Discussionmentioning

confidence: 99%

Isolation and Genetic Characterization of H5N2 Influenza Viruses from Pigs in Korea

Lee

Pascua

Song

et al. 2009

J Virol

View full text Add to dashboard Cite

“…Introduction of residue 627K enhanced the activity of the Bav and 50-92 polymerases to a level similar to that shown by the Eng195 polymerase, an influenza virus polymerase capable of replication in pigs. Moreover, the E627K mutation occurred spontaneously when a restricted reassortant virus was used to infect pigs (125). It is not clear why most porcine influenza viruses derived directly from an avian source do not contain the 627K motif in PB2.…”

Section: Discussionmentioning

confidence: 99%

Investigation of Influenza Virus Polymerase Activity in Pig Cells

Moncorgé

Long

Cauldwell

et al. 2013

J Virol

View full text Add to dashboard Cite

bReassortant influenza viruses with combinations of avian, human, and/or swine genomic segments have been detected frequently in pigs. As a consequence, pigs have been accused of being a "mixing vessel" for influenza viruses. This implies that pig cells support transcription and replication of avian influenza viruses, in contrast to human cells, in which most avian influenza virus polymerases display limited activity. Although influenza virus polymerase activity has been studied in human and avian cells for many years by use of a minigenome assay, similar investigations in pig cells have not been reported. We developed the first minigenome assay for pig cells and compared the activities of polymerases of avian or human influenza virus origin in pig, human, and avian cells. We also investigated in pig cells the consequences of some known mammalian host range determinants that enhance influenza virus polymerase activity in human cells, such as PB2 mutations E627K, D701N, G590S/Q591R, and T271A. The two typical avian influenza virus polymerases used in this study were poorly active in pig cells, similar to what is seen in human cells, and mutations that adapt the avian influenza virus polymerase for human cells also increased activity in pig cells. In contrast, a different pattern was observed in avian cells. Finally, highly pathogenic avian influenza virus H5N1 polymerase activity was tested because this subtype has been reported to replicate only poorly in pigs. H5N1 polymerase was active in swine cells, suggesting that other barriers restrict these viruses from becoming endemic in pigs.

show abstract

PB2 Protein of a Highly Pathogenic Avian Influenza Virus Strain A/chicken/Yamaguchi/7/2004 (H5N1) Determines Its Replication Potential in Pigs

Cited by 70 publications

References 60 publications

Adaptive strategies of the influenza virus polymerase for replication in humans

Adaptive strategies of the influenza virus polymerase for replication in humans

Isolation and Genetic Characterization of H5N2 Influenza Viruses from Pigs in Korea

Investigation of Influenza Virus Polymerase Activity in Pig Cells

Contact Info

Product

Resources

About