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The evolutionary genetics and emergence of avian influenza viruses in wild birds.

Dugan VG, Chen R, Spiro DJ, Sengamalay N, Zaborsky J, Ghedin E, Nolting J, Swayne DE, Runstadler JA, Happ GM, Senne DA, Wang R, Slemons RD, Holmes EC, Taubenberger JK - PLoS Pathog. (2008)

Bottom Line: These isolates represented 29 type A influenza virus hemagglutinin (HA) and neuraminidase (NA) subtype combinations, with up to 26% of isolates showing evidence of mixed subtype infection.Through a phylogenetic analysis of the largest data set of AIV genomes compiled to date, we were able to document a remarkably high rate of genome reassortment, with no clear pattern of gene segment association and occasional inter-hemisphere gene segment migration and reassortment.From this, we propose that AIV in wild birds forms transient "genome constellations," continually reshuffled by reassortment, in contrast to the spread of a limited number of stable genome constellations that characterizes the evolution of mammalian-adapted influenza A viruses.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.

ABSTRACT
We surveyed the genetic diversity among avian influenza virus (AIV) in wild birds, comprising 167 complete viral genomes from 14 bird species sampled in four locations across the United States. These isolates represented 29 type A influenza virus hemagglutinin (HA) and neuraminidase (NA) subtype combinations, with up to 26% of isolates showing evidence of mixed subtype infection. Through a phylogenetic analysis of the largest data set of AIV genomes compiled to date, we were able to document a remarkably high rate of genome reassortment, with no clear pattern of gene segment association and occasional inter-hemisphere gene segment migration and reassortment. From this, we propose that AIV in wild birds forms transient "genome constellations," continually reshuffled by reassortment, in contrast to the spread of a limited number of stable genome constellations that characterizes the evolution of mammalian-adapted influenza A viruses.

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The fitness landscapes of avian influenza virus.(a) The fitness landscapes observed in HA, NA and NS, and represented here by NA. Each colored cone represents an individual subtype. These subtypes are connected by a bifurcating tree. The lack of ‘intermediate’ subtypes – those falling below the pink disc – reflects major valleys in fitness, such that any virus falling in this area will experience a major reduction in fitness, most likely due to an elevated cross-protective immune response. Occasionally, individual subtypes jump species barriers and spread in new hosts (such as humans), where they experience a continued selection pressure and hence accumulate amino acid substitutions in a progressive manner, as shown. (b) The fitness landscapes observed in the remaining internal protein segments of avian influenza virus – PB2, PB1, PA, NP and M (represented by different colors). In this case, there is little functional difference among the genetic variants of each segment, so that the fitness landscape is flat. This equivalence in fitness among genome constellations also means that reassortment is frequent among them (as reassortants suffer no fitness cost), represented by the horizontal lines connected each internal gene segment.
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ppat-1000076-g004: The fitness landscapes of avian influenza virus.(a) The fitness landscapes observed in HA, NA and NS, and represented here by NA. Each colored cone represents an individual subtype. These subtypes are connected by a bifurcating tree. The lack of ‘intermediate’ subtypes – those falling below the pink disc – reflects major valleys in fitness, such that any virus falling in this area will experience a major reduction in fitness, most likely due to an elevated cross-protective immune response. Occasionally, individual subtypes jump species barriers and spread in new hosts (such as humans), where they experience a continued selection pressure and hence accumulate amino acid substitutions in a progressive manner, as shown. (b) The fitness landscapes observed in the remaining internal protein segments of avian influenza virus – PB2, PB1, PA, NP and M (represented by different colors). In this case, there is little functional difference among the genetic variants of each segment, so that the fitness landscape is flat. This equivalence in fitness among genome constellations also means that reassortment is frequent among them (as reassortants suffer no fitness cost), represented by the horizontal lines connected each internal gene segment.

Mentions: The AIV genomic data available here suggest a complex interplay of evolutionary processes. That discrete HA and NA subtypes, as well as the 2 divergent NS alleles, are maintained in the face of frequent reassortment strongly suggests that each represents a peak on a fitness landscape shaped by cross-immunity (Figure 4a). Under this hypothesis, ‘intermediate’ HA/NA/NS alleles would be selected against because they generate more widespread herd immunity, corresponding to fitness valleys. Indeed, it is the likely lack of immunological cross-protection at the subtype level that allows the frequent mixed infections described here (although mixed infections may also occur in young, immunologically naïve birds). Further, in most cases these divergent HA, NA and NS alleles circulate in the same bird species in the same geographical regions, compatible with their divergence under sympatry. In addition, 3 of the most closely related pairs of HA subtypes contain an HA that is rarely isolated or limited geographically or by host species restriction, implying that their dispersion is inhibited by existing immunity; H14 has only been isolated rarely in Southern Russia, H15 only in Australia, and H16 has only been described in gulls. The possible exception is H2–H5, where both subtypes have been isolated from a variety of bird species in a global distribution. Although these may represent more recent occurrences of allopatric speciation, antigenic cross-reactivity between the H2–H5, H7–H15, H4–H14 pairs was recently demonstrated [51], again compatible with the sympatric model. Further support for possible cross-immunity between these subtypes would require experimental challenge studies.


The evolutionary genetics and emergence of avian influenza viruses in wild birds.

Dugan VG, Chen R, Spiro DJ, Sengamalay N, Zaborsky J, Ghedin E, Nolting J, Swayne DE, Runstadler JA, Happ GM, Senne DA, Wang R, Slemons RD, Holmes EC, Taubenberger JK - PLoS Pathog. (2008)

The fitness landscapes of avian influenza virus.(a) The fitness landscapes observed in HA, NA and NS, and represented here by NA. Each colored cone represents an individual subtype. These subtypes are connected by a bifurcating tree. The lack of ‘intermediate’ subtypes – those falling below the pink disc – reflects major valleys in fitness, such that any virus falling in this area will experience a major reduction in fitness, most likely due to an elevated cross-protective immune response. Occasionally, individual subtypes jump species barriers and spread in new hosts (such as humans), where they experience a continued selection pressure and hence accumulate amino acid substitutions in a progressive manner, as shown. (b) The fitness landscapes observed in the remaining internal protein segments of avian influenza virus – PB2, PB1, PA, NP and M (represented by different colors). In this case, there is little functional difference among the genetic variants of each segment, so that the fitness landscape is flat. This equivalence in fitness among genome constellations also means that reassortment is frequent among them (as reassortants suffer no fitness cost), represented by the horizontal lines connected each internal gene segment.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2387073&req=5

ppat-1000076-g004: The fitness landscapes of avian influenza virus.(a) The fitness landscapes observed in HA, NA and NS, and represented here by NA. Each colored cone represents an individual subtype. These subtypes are connected by a bifurcating tree. The lack of ‘intermediate’ subtypes – those falling below the pink disc – reflects major valleys in fitness, such that any virus falling in this area will experience a major reduction in fitness, most likely due to an elevated cross-protective immune response. Occasionally, individual subtypes jump species barriers and spread in new hosts (such as humans), where they experience a continued selection pressure and hence accumulate amino acid substitutions in a progressive manner, as shown. (b) The fitness landscapes observed in the remaining internal protein segments of avian influenza virus – PB2, PB1, PA, NP and M (represented by different colors). In this case, there is little functional difference among the genetic variants of each segment, so that the fitness landscape is flat. This equivalence in fitness among genome constellations also means that reassortment is frequent among them (as reassortants suffer no fitness cost), represented by the horizontal lines connected each internal gene segment.
Mentions: The AIV genomic data available here suggest a complex interplay of evolutionary processes. That discrete HA and NA subtypes, as well as the 2 divergent NS alleles, are maintained in the face of frequent reassortment strongly suggests that each represents a peak on a fitness landscape shaped by cross-immunity (Figure 4a). Under this hypothesis, ‘intermediate’ HA/NA/NS alleles would be selected against because they generate more widespread herd immunity, corresponding to fitness valleys. Indeed, it is the likely lack of immunological cross-protection at the subtype level that allows the frequent mixed infections described here (although mixed infections may also occur in young, immunologically naïve birds). Further, in most cases these divergent HA, NA and NS alleles circulate in the same bird species in the same geographical regions, compatible with their divergence under sympatry. In addition, 3 of the most closely related pairs of HA subtypes contain an HA that is rarely isolated or limited geographically or by host species restriction, implying that their dispersion is inhibited by existing immunity; H14 has only been isolated rarely in Southern Russia, H15 only in Australia, and H16 has only been described in gulls. The possible exception is H2–H5, where both subtypes have been isolated from a variety of bird species in a global distribution. Although these may represent more recent occurrences of allopatric speciation, antigenic cross-reactivity between the H2–H5, H7–H15, H4–H14 pairs was recently demonstrated [51], again compatible with the sympatric model. Further support for possible cross-immunity between these subtypes would require experimental challenge studies.

Bottom Line: These isolates represented 29 type A influenza virus hemagglutinin (HA) and neuraminidase (NA) subtype combinations, with up to 26% of isolates showing evidence of mixed subtype infection.Through a phylogenetic analysis of the largest data set of AIV genomes compiled to date, we were able to document a remarkably high rate of genome reassortment, with no clear pattern of gene segment association and occasional inter-hemisphere gene segment migration and reassortment.From this, we propose that AIV in wild birds forms transient "genome constellations," continually reshuffled by reassortment, in contrast to the spread of a limited number of stable genome constellations that characterizes the evolution of mammalian-adapted influenza A viruses.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.

ABSTRACT
We surveyed the genetic diversity among avian influenza virus (AIV) in wild birds, comprising 167 complete viral genomes from 14 bird species sampled in four locations across the United States. These isolates represented 29 type A influenza virus hemagglutinin (HA) and neuraminidase (NA) subtype combinations, with up to 26% of isolates showing evidence of mixed subtype infection. Through a phylogenetic analysis of the largest data set of AIV genomes compiled to date, we were able to document a remarkably high rate of genome reassortment, with no clear pattern of gene segment association and occasional inter-hemisphere gene segment migration and reassortment. From this, we propose that AIV in wild birds forms transient "genome constellations," continually reshuffled by reassortment, in contrast to the spread of a limited number of stable genome constellations that characterizes the evolution of mammalian-adapted influenza A viruses.

Show MeSH
Related in: MedlinePlus