Human HA and polymerase subunit PB2 proteins confer transmission of an avian influenza virus through the air

Hoeven, Neal Van; Pappas, Claudia; Belser, Jessica A.; Maines, Taronna R.; Zeng, Hui; Garcı́a-Sastre, Adolfo; Sasisekharan, Ram; Katz, Jacqueline M.; Tumpey, Terrence M.

doi:10.1073/pnas.0813172106

Cited by 204 publications

(234 citation statements)

References 37 publications

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“…The ferret model recapitulates the efficient transmission of seasonal influenza viruses and the poor transmission of avian influenza viruses in humans (25,(29)(30)(31). The transmission kinetics and efficient RD transmission of the 2010 and 2011 A(H3N2)v viruses is comparable to that observed with seasonal influenza viruses in ferrets (23,29,32,33).…”

Section: Discussionmentioning

confidence: 72%

“…Human-adapted seasonal influenza H1 and H3 HA demonstrate high specificity for α2-6-sialylated glycans, and it has been postulated that efficient and sustained human-to-human transmission of influenza viruses requires an α2,6 sialic acid receptor-binding preference (21,22,27,30,32,41). Bateman et al demonstrated that TRS H3N2 viruses isolated in the late 1990s bound exclusively to α2-6-sialylated glycans (42).…”

Section: Discussionmentioning

confidence: 99%

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Pathogenesis and transmission of swine origin A(H3N2)v influenza viruses in ferrets

Pearce

Jayaraman

Pappas

et al. 2012

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

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111

112

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Recent isolation of a novel swine-origin influenza A H3N2 variant virus [A(H3N2)v] from humans in the United States has raised concern over the pandemic potential of these viruses. Here, we analyzed the virulence, transmissibility, and receptor-binding preference of four A(H3N2)v influenza viruses isolated from humans in 2009, 2010, and 2011. High titers of infectious virus were detected in nasal turbinates and nasal wash samples of A(H3N2)v-inoculated ferrets. All four A(H3N2)v viruses possessed the capacity to spread efficiently between cohoused ferrets, and the 2010 and 2011 A(H3N2)v isolates transmitted efficiently to naïve ferrets by respiratory droplets. A dose-dependent glycan array analysis of A(H3N2)v showed a predominant binding to α2-6–sialylated glycans, similar to human-adapted influenza A viruses. We further tested the viral replication efficiency of A(H3N2)v viruses in a relevant cell line, Calu-3, derived from human bronchial epithelium. The A(H3N2)v viruses replicated in Calu-3 cells to significantly higher titers compared with five common seasonal H3N2 influenza viruses. These findings suggest that A(H3N2)v viruses have the capacity for efficient replication and transmission in mammals and underscore the need for continued public health surveillance.

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Section: Discussionmentioning

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Pathogenesis and transmission of swine origin A(H3N2)v influenza viruses in ferrets

Pearce

Jayaraman

Pappas

et al. 2012

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

Self Cite

111

112

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“…4F and when comparing the viral titers and length of shedding in respiratory droplet contacts from RCP10 and 2RCP10:6M98. The internal genes have been implicated in transmission not only within avian species (20)(21)(22) but also from avian to mammalian species (23,24). A complete set of viruses tested and their transmission phenotype are listed (Table 4 and supporting information (SI) Fig.…”

Section: Adaptive Mutations On Rcp10 Surface Proteins Support Respiramentioning

confidence: 99%

Minimal molecular constraints for respiratory droplet transmission of an avian–human H9N2 influenza A virus

Sorrell

Wan

Araya

et al. 2009

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

212

204

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Pandemic influenza requires interspecies transmission of an influenza virus with a novel hemagglutinin (HA) subtytpe that can adapt to its new host through either reassortment or point mutations and transmit by aerosolized respiratory droplets. Two previous pandemics of 1957 and 1968 resulted from the reassortment of low pathogenic avian viruses and human subtypes of that period; however, conditions leading to a pandemic virus are still poorly understood. Given the endemic situation of avian H9N2 influenza with human-like receptor specificity in Eurasia and its occasional transmission to humans and pigs, we wanted to determine whether an avian-human H9N2 reassortant could gain respiratory transmission in a mammalian animal model, the ferret. Here we show that following adaptation in the ferret, a reassortant virus carrying the surface proteins of an avian H9N2 in a human H3N2 backbone can transmit efficiently via respiratory droplets, creating a clinical infection similar to human influenza infections. Minimal changes at the protein level were found in this virus capable of respiratory droplet transmission. A reassortant virus expressing only the HA and neuraminidase (NA) of the ferret-adapted virus was able to account for the transmissibility, suggesting that currently circulating avian H9N2 viruses require little adaptation in mammals following acquisition of all human virus internal genes through reassortment. Hemagglutinin inhibition (HI) analysis showed changes in the antigenic profile of the virus, which carries profound implications for vaccine seed stock preparation against avian H9N2 influenza. This report illustrates that aerosolized respiratory transmission is not exclusive to current human H1, H2, and H3 influenza subtypes.aerosol ͉ ferrets ͉ contact ͉ pandemic ͉ preparedness

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“…The PB2 subunit interacts with PA in the cytoplasm initially and is subsequently transported as a dimer into the nucleus [10]. The viral RNA polymerase complex is important for the efficient propagation of the virus in the host and for its adaptation to new hosts [11], and considered as a major determinant of the pathogenicity of the 1918 pandemic virus [12]. The mutations in PB2 protein can affect the virulence of influenza A virus [13], change RNA binding activity [14,15], and contribute to intra-and inter-host transmission in diverse virus backgrounds [15,16].…”

Section: Introductionmentioning

confidence: 99%

Trends in global warming and evolution of polymerase basic protein 2 family from influenza a virus

Yan¹,

Wu²

2009

JBiSE

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Both global warming and influenza trouble humans in varying ways, therefore it is important to study the trends in both global warming and evolution of influenza A virus, in particular, proteins from influenza A virus. Recently, we have conducted two studies along this line to determine the trends between global warming and polymerase acidic protein as well as matrix protein 2. Although these two studies reveal some interesting findings, many studies are still in need because at least there are ten different proteins in influenza A virus. In this study, we analyze the trends in global warming and evolution of polymerase basic protein 2 (PB2) from influenza A virus. The PB2 evolution from 1956 to 2008 was defined using the unpredictable portion of amino-acid pair. Then the trend in this evolution was compared with the trend in the global temperature, the temperature in north and south hemispheres, and the temperature in influenza A virus sampling site and species carrying influenza A virus. The results show the similar trends in global warming and in PB2 evolution, which are in good agreement with our previous studies in polymerase acidic protein and matrix protein 2 from influenza A virus.

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Human HA and polymerase subunit PB2 proteins confer transmission of an avian influenza virus through the air

Cited by 204 publications

References 37 publications

Pathogenesis and transmission of swine origin A(H3N2)v influenza viruses in ferrets

Pathogenesis and transmission of swine origin A(H3N2)v influenza viruses in ferrets

Minimal molecular constraints for respiratory droplet transmission of an avian–human H9N2 influenza A virus

Trends in global warming and evolution of polymerase basic protein 2 family from influenza a virus

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