Complete-proteome mapping of human influenza A adaptive mutations

Implications for human transmissibility of zoonotic strains

Olivo Miotto, A. T. Heiny, Randy Albrecht, Adolfo García-Sastre, Tin Wee Tan, J. Thomas August, Vladimir Brusic

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Background: There is widespread concern that H5N1 avian influenza A viruses will emerge as a pandemic threat, if they become capable of human-to-human (H2H) transmission. Avian strains lack this capability, which suggests that it requires important adaptive mutations. We performed a large-scale comparative analysis of proteins from avian and human strains, to produce a catalogue of mutations associated with H2H transmissibility, and to detect their presence in avian isolates. Methodology/Principal Findings:We constructed a dataset of influenza A protein sequences from 92,343 public database records. Human and avian sequence subsets were compared, using a method based on mutual information, to identify characteristic sites where human isolates present conserved mutations. The resulting catalogue comprises 68 characteristic sites in eight internal proteins. Subtype variability prevented the identification of adaptive mutations in the hemagglutinin and neuraminidase proteins. The high number of sites in the ribonucleoprotein complex suggests interdependence between mutations in multiple proteins. Characteristic sites are often clustered within known functional regions, suggesting their functional roles in cellular processes. By isolating and concatenating characteristic site residues, we defined adaptation signatures, which summarize the adaptive potential of specific isolates. Most adaptive mutations emerged within three decades after the 1918 pandemic, and have remained remarkably stable thereafter. Two lineages with stable internal protein constellations have circulated among humans without reassorting. On the contrary, H5N1 avian and swine viruses reassort frequently, causing both gains and losses of adaptive mutations. Conclusions: Human host adaptation appears to be complex and systemic, involving nearly all influenza proteins. Adaptation signatures suggest that the ability of H5N1 strains to infect humans is related to the presence of an unusually high number of adaptive mutations. However, these mutations appear unstable, suggesting low pandemic potential of H5N1 in its current form. In addition, adaptation signatures indicate that pandemic H1N1/09 strain possesses multiple human-transmissibility mutations, though not an unusually high number with respect to swine strains that infected humans in the past. Adaptation signatures provide a novel tool for identifying zoonotic strains with the potential to infect humans.

Original languageEnglish
Article numbere9025
JournalPLoS One
Volume5
Issue number2
DOIs
Publication statusPublished - Feb 3 2010
Externally publishedYes

Fingerprint

human influenza
Zoonoses
Proteome
proteome
Human Influenza
mutation
Mutation
Proteins
Pandemics
pandemic
Viruses
Avian Proteins
proteins
Ribonucleoproteins
Hemagglutinins
Neuraminidase
influenza
Swine
ribonucleoproteins
swine

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Miotto, O., Heiny, A. T., Albrecht, R., García-Sastre, A., Tan, T. W., August, J. T., & Brusic, V. (2010). Complete-proteome mapping of human influenza A adaptive mutations: Implications for human transmissibility of zoonotic strains. PLoS One, 5(2), [e9025]. https://doi.org/10.1371/journal.pone.0009025

Complete-proteome mapping of human influenza A adaptive mutations : Implications for human transmissibility of zoonotic strains. / Miotto, Olivo; Heiny, A. T.; Albrecht, Randy; García-Sastre, Adolfo; Tan, Tin Wee; August, J. Thomas; Brusic, Vladimir.

In: PLoS One, Vol. 5, No. 2, e9025, 03.02.2010.

Research output: Contribution to journalArticle

Miotto, O, Heiny, AT, Albrecht, R, García-Sastre, A, Tan, TW, August, JT & Brusic, V 2010, 'Complete-proteome mapping of human influenza A adaptive mutations: Implications for human transmissibility of zoonotic strains', PLoS One, vol. 5, no. 2, e9025. https://doi.org/10.1371/journal.pone.0009025
Miotto, Olivo ; Heiny, A. T. ; Albrecht, Randy ; García-Sastre, Adolfo ; Tan, Tin Wee ; August, J. Thomas ; Brusic, Vladimir. / Complete-proteome mapping of human influenza A adaptive mutations : Implications for human transmissibility of zoonotic strains. In: PLoS One. 2010 ; Vol. 5, No. 2.
@article{238bc3b364ac4776b5003a1204bf5c12,
title = "Complete-proteome mapping of human influenza A adaptive mutations: Implications for human transmissibility of zoonotic strains",
abstract = "Background: There is widespread concern that H5N1 avian influenza A viruses will emerge as a pandemic threat, if they become capable of human-to-human (H2H) transmission. Avian strains lack this capability, which suggests that it requires important adaptive mutations. We performed a large-scale comparative analysis of proteins from avian and human strains, to produce a catalogue of mutations associated with H2H transmissibility, and to detect their presence in avian isolates. Methodology/Principal Findings:We constructed a dataset of influenza A protein sequences from 92,343 public database records. Human and avian sequence subsets were compared, using a method based on mutual information, to identify characteristic sites where human isolates present conserved mutations. The resulting catalogue comprises 68 characteristic sites in eight internal proteins. Subtype variability prevented the identification of adaptive mutations in the hemagglutinin and neuraminidase proteins. The high number of sites in the ribonucleoprotein complex suggests interdependence between mutations in multiple proteins. Characteristic sites are often clustered within known functional regions, suggesting their functional roles in cellular processes. By isolating and concatenating characteristic site residues, we defined adaptation signatures, which summarize the adaptive potential of specific isolates. Most adaptive mutations emerged within three decades after the 1918 pandemic, and have remained remarkably stable thereafter. Two lineages with stable internal protein constellations have circulated among humans without reassorting. On the contrary, H5N1 avian and swine viruses reassort frequently, causing both gains and losses of adaptive mutations. Conclusions: Human host adaptation appears to be complex and systemic, involving nearly all influenza proteins. Adaptation signatures suggest that the ability of H5N1 strains to infect humans is related to the presence of an unusually high number of adaptive mutations. However, these mutations appear unstable, suggesting low pandemic potential of H5N1 in its current form. In addition, adaptation signatures indicate that pandemic H1N1/09 strain possesses multiple human-transmissibility mutations, though not an unusually high number with respect to swine strains that infected humans in the past. Adaptation signatures provide a novel tool for identifying zoonotic strains with the potential to infect humans.",
author = "Olivo Miotto and Heiny, {A. T.} and Randy Albrecht and Adolfo Garc{\'i}a-Sastre and Tan, {Tin Wee} and August, {J. Thomas} and Vladimir Brusic",
year = "2010",
month = "2",
day = "3",
doi = "10.1371/journal.pone.0009025",
language = "English",
volume = "5",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "2",

}

TY - JOUR

T1 - Complete-proteome mapping of human influenza A adaptive mutations

T2 - Implications for human transmissibility of zoonotic strains

AU - Miotto, Olivo

AU - Heiny, A. T.

AU - Albrecht, Randy

AU - García-Sastre, Adolfo

AU - Tan, Tin Wee

AU - August, J. Thomas

AU - Brusic, Vladimir

PY - 2010/2/3

Y1 - 2010/2/3

N2 - Background: There is widespread concern that H5N1 avian influenza A viruses will emerge as a pandemic threat, if they become capable of human-to-human (H2H) transmission. Avian strains lack this capability, which suggests that it requires important adaptive mutations. We performed a large-scale comparative analysis of proteins from avian and human strains, to produce a catalogue of mutations associated with H2H transmissibility, and to detect their presence in avian isolates. Methodology/Principal Findings:We constructed a dataset of influenza A protein sequences from 92,343 public database records. Human and avian sequence subsets were compared, using a method based on mutual information, to identify characteristic sites where human isolates present conserved mutations. The resulting catalogue comprises 68 characteristic sites in eight internal proteins. Subtype variability prevented the identification of adaptive mutations in the hemagglutinin and neuraminidase proteins. The high number of sites in the ribonucleoprotein complex suggests interdependence between mutations in multiple proteins. Characteristic sites are often clustered within known functional regions, suggesting their functional roles in cellular processes. By isolating and concatenating characteristic site residues, we defined adaptation signatures, which summarize the adaptive potential of specific isolates. Most adaptive mutations emerged within three decades after the 1918 pandemic, and have remained remarkably stable thereafter. Two lineages with stable internal protein constellations have circulated among humans without reassorting. On the contrary, H5N1 avian and swine viruses reassort frequently, causing both gains and losses of adaptive mutations. Conclusions: Human host adaptation appears to be complex and systemic, involving nearly all influenza proteins. Adaptation signatures suggest that the ability of H5N1 strains to infect humans is related to the presence of an unusually high number of adaptive mutations. However, these mutations appear unstable, suggesting low pandemic potential of H5N1 in its current form. In addition, adaptation signatures indicate that pandemic H1N1/09 strain possesses multiple human-transmissibility mutations, though not an unusually high number with respect to swine strains that infected humans in the past. Adaptation signatures provide a novel tool for identifying zoonotic strains with the potential to infect humans.

AB - Background: There is widespread concern that H5N1 avian influenza A viruses will emerge as a pandemic threat, if they become capable of human-to-human (H2H) transmission. Avian strains lack this capability, which suggests that it requires important adaptive mutations. We performed a large-scale comparative analysis of proteins from avian and human strains, to produce a catalogue of mutations associated with H2H transmissibility, and to detect their presence in avian isolates. Methodology/Principal Findings:We constructed a dataset of influenza A protein sequences from 92,343 public database records. Human and avian sequence subsets were compared, using a method based on mutual information, to identify characteristic sites where human isolates present conserved mutations. The resulting catalogue comprises 68 characteristic sites in eight internal proteins. Subtype variability prevented the identification of adaptive mutations in the hemagglutinin and neuraminidase proteins. The high number of sites in the ribonucleoprotein complex suggests interdependence between mutations in multiple proteins. Characteristic sites are often clustered within known functional regions, suggesting their functional roles in cellular processes. By isolating and concatenating characteristic site residues, we defined adaptation signatures, which summarize the adaptive potential of specific isolates. Most adaptive mutations emerged within three decades after the 1918 pandemic, and have remained remarkably stable thereafter. Two lineages with stable internal protein constellations have circulated among humans without reassorting. On the contrary, H5N1 avian and swine viruses reassort frequently, causing both gains and losses of adaptive mutations. Conclusions: Human host adaptation appears to be complex and systemic, involving nearly all influenza proteins. Adaptation signatures suggest that the ability of H5N1 strains to infect humans is related to the presence of an unusually high number of adaptive mutations. However, these mutations appear unstable, suggesting low pandemic potential of H5N1 in its current form. In addition, adaptation signatures indicate that pandemic H1N1/09 strain possesses multiple human-transmissibility mutations, though not an unusually high number with respect to swine strains that infected humans in the past. Adaptation signatures provide a novel tool for identifying zoonotic strains with the potential to infect humans.

UR - http://www.scopus.com/inward/record.url?scp=77949348063&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77949348063&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0009025

DO - 10.1371/journal.pone.0009025

M3 - Article

VL - 5

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 2

M1 - e9025

ER -