Correlated mutations in the four influenza proteins   essential for viral RNA synthesis, host adaptation,  and virulence: NP, PA, PB1, and PB2

Hu, Wei

doi:10.4236/ns.2010.210141

Cited by 11 publications

(7 citation statements)

References 25 publications

(27 reference statements)

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“…Site PB2_627 in avian H5N1 was connected to PB2_ 649 and PB2_451 that belonged to a group of mutu nnected sites, thereby revealing several potential sites sites in PB1, PA, and NP of human H5N1 (Figure 7). Importantly, here PB2_524 actually was a hub site that connected many sites in PB2 of human H5N1, including site PB2_590, one of the two sites of SR polymorphism discovered in [40] that could enhance polymerase activity in human cells. The connection between PB2_590 and PB2_524 in human H5N1 suggested that the change at site 590 might be associated with the change at site 524, as well as other sites connected by site 524, which enlarged the number of potential sites that might influence site 590.…”

Section: Correlated Site Pairs In Pb2 Prmentioning

confidence: 93%

“…Despite intense research on H5N1, further understanding of the molecular mechanisms for avian influenza virus to cross species boundaries to infect humans is of major interest. Using the computational methodology developed in [14][15][16][17][18][19][20][21][22][23][24], the current proteomic study aimed to discover molecular characteristics in the proteins of avian and human H5N1 viruses in Asia and to identify viral traits including HA binding features that might promote the transmission of H5N1 from birds to humans.…”

Section: Introductionmentioning

confidence: 99%

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Molecular Features of Highly Pathogenic Avian and Human H5N1 Influenza A Viruses in Asia

2012

CMB

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The highly pathogenic avian H5N1 influenza virus could infect humans with high mortality rate, even though it has not yet become efficiently transmissible among humans. This proteomic study investigated the molecular basis of interspecies transmission and host range of this lethal virus in Asia, due to its potential pandemic threat. Although there are host markers located in previous research between general avian and human influenza viruses, the novelty of our work was to uncover host markers between highly pathogenic avian and human H5N1 viruses in Asia. Many host markers we found were not present in the previous general markers, thus expanding the current repertoire of host markers with these strain-specific host markers. Ranked by their order of importance, the top 10 host markers discovered in this report were PB2_627, HA_325, NS1_205, PB2_524, HA_86, NA_201, NP_373, NS1_7, HA_156, NA_74, confirming our current knowledge that PB2_627 is the most critical site for distinguishing avian and human H5N1. We also identified several naturally-occurred mutations in the HA protein that might shift the receptor binding preference of Asian avian H5N1, since early detection of mutations that might lead to emergence of a new pandemic virus is of prime importance. Finally, we analyzed the distinctive interaction patterns within and between proteins of avian and human H5N1 in Asia at protein level and individual residue level. From multiple viewpoints, our findings reinforced the experimental observation that multiple genes of Asian avian H5N1 are involved in its gradual adaptation to human hosts.

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Section: Correlated Site Pairs In Pb2 Prmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Molecular Features of Highly Pathogenic Avian and Human H5N1 Influenza A Viruses in Asia

2012

CMB

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“…Inspired by the work in [1], which used three 2013 H7N9 strains collected from three patients in China, this study employed the methodology developed in [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] to investigate this novel avian-origin H7N9 virus with five 2013 H7N9 strains in China. Our aim was to discover gene sequence difference between this new virus and the previous avian H7N9 and identify and then analyze mutations in the HA protein that could help this virus making its adaptation from avian to human hosts.…”

Section: Introductionmentioning

confidence: 99%

Receptor binding specificity and sequence comparison of a novel avian-origin H7N9 virus in China

Hu¹

2013

JBiSE

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Avian influenza such as H5N1 could infect humans and cause great health concern due to its high mortality rate. In March 2013, a novel reassortant avianorigin influenza A (H7N9) virus was found in several patients with severe respiratory illness in China. Since then, at least 82 people in China have been infected with this new virus and 17 have died from this virus. The question of how these people were infected with this virus and whether this virus will spread among people remains an urgent topic for research. This study took an early investigation of this virus by comparing the collected viral genome sequences of 2013 H7N9 in China against those of previous avian H7N9 and examined the receptor binding specificity of this new virus. This virus was found to be very different from the previous avian H7N9 viruses and surprisingly many of the internal proteins of 2013 H7N9 from the avian and human hosts in China were either identical or similar. Our analysis of the HA protein of this virus implied that the current strains of 2013 H7N9 in China displayed avian type receptors as their primary binding preference and human type receptors as secondary. For pandemic risk assessment, we also detected 23 mutations, including a few well known for host adaptation, in the HA1 domain of the HA protein from this virus. Each mutation was quantified for its impact on the recaptor binding selection using a bioinformatics approach. Collectively these current mutations tended to decrease the HA binding affinity for avian type recaptors and increase that for human type receptors, which could enhance the ability of this virus to infect humans.

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“…In light of the emergence of this novel H7N9 virus in China, we were very curious to learn, employing the methodology developed in [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25], the individual as well as the collective impact of the mutations identified in [4,6] on the receptor selection of H5N1. At the same time, beyond the groups of HA mutations examined in these two studies we wanted to seek other possible groups of mutations that could render similar effect on HA receptor binding preference to those found in [4,6].…”

Section: Introductionmentioning

confidence: 99%

Mutations in Hemagglutinin of H5N1 Influenza That Switch Receptor Specificity from Avian to Human Types

Hu¹

2013

CMB

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The avian H7N9 influenza outbreak in 2013 resulted from an unprecedented incidence of influenza transmission to humans from infected poultry. The majority of human H7N9 isolates contained a hemagglutinin (HA) mutation (Q226L) that has previously been associated with a switch in receptor specificity from avian-type (NeuAcα2-3Gal) to human-type (NeuAcα2-6Gal), as documented for the avian progenitors of the 1957 (H2N2) and 1968 (H3N2) human influenza pandemic viruses. While this raised concern that the H7N9 virus was adapting to humans, the mutation was not sufficient to switch the receptor specificity of H7N9, and has not resulted in sustained transmission in humans. To determine if the H7 HA was capable of acquiring human-type receptor specificity, we conducted mutation analyses. Remarkably, three amino acid mutations conferred a switch in specificity for human-type receptors that resembled the specificity of the 2009 human H1 pandemic virus, and promoted binding to human trachea epithelial cells. Author summary Influenza A virus of the H7N9 subtype continues to cross the species barrier from poultry to humans. This zoonotic ability is remarkable as the virus retains specificity to avian-type receptors. To effectively transmit between humans, the virus needs to acquire human-type receptor specificity. In this study, we show that recombinant H7 proteins PLOS Pathogens | https://doi.org/10.1371/journal.ppat.

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Correlated mutations in the four influenza proteins essential for viral RNA synthesis, host adaptation, and virulence: NP, PA, PB1, and PB2

Cited by 11 publications

References 25 publications

Molecular Features of Highly Pathogenic Avian and Human H5N1 Influenza A Viruses in Asia

Molecular Features of Highly Pathogenic Avian and Human H5N1 Influenza A Viruses in Asia

Receptor binding specificity and sequence comparison of a novel avian-origin H7N9 virus in China

Mutations in Hemagglutinin of H5N1 Influenza That Switch Receptor Specificity from Avian to Human Types

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