Limits...
Proteinquakes in the evolution of influenza virus hemagglutinin (A/H1N1) under opposing migration and vaccination pressures.

Phillips JC - Biomed Res Int (2015)

Bottom Line: Here we show that, while HA evolution is much more complex than NA evolution, it still shows abrupt punctuation changes linked to punctuation changes of NA.HA exhibits proteinquakes, which resemble earthquakes and are related to hydropathic shifting of sialic acid binding regions.Our comprehensive results present a historical (1945-2011) panorama of HA evolution over thousands of strains and are consistent with many studies of HA and NA interactions based on a few mutations of a few strains.

View Article: PubMed Central - PubMed

Affiliation: Department of Physics and Astronomy, Rutgers University, Piscataway, NJ 08854, USA.

ABSTRACT
Influenza virus contains two highly variable envelope glycoproteins, hemagglutinin (HA) and neuraminidase (NA). Here we show that, while HA evolution is much more complex than NA evolution, it still shows abrupt punctuation changes linked to punctuation changes of NA. HA exhibits proteinquakes, which resemble earthquakes and are related to hydropathic shifting of sialic acid binding regions. HA proteinquakes based on shifting sialic acid interactions are required for optimal balance between the receptor-binding and receptor-destroying activities of HA and NA for efficient virus replication. Our comprehensive results present a historical (1945-2011) panorama of HA evolution over thousands of strains and are consistent with many studies of HA and NA interactions based on a few mutations of a few strains.

Show MeSH

Related in: MedlinePlus

Sketch of chain A1 〈ψ(aa, 1)〉 evolution, with Fort Dix outbreak and swine flu peak (before vaccination program) indicated. The HA 〈ψ(aa, 1)〉 trends seen here parallel those for NA tabulated in [5].
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4309245&req=5

fig5: Sketch of chain A1 〈ψ(aa, 1)〉 evolution, with Fort Dix outbreak and swine flu peak (before vaccination program) indicated. The HA 〈ψ(aa, 1)〉 trends seen here parallel those for NA tabulated in [5].

Mentions: Perhaps the simplest difference between HA and NA profiles is the fact that NA profiles have overall ψMZ averages = 〈ψMZ〉 nearer 155 (hydroneutral, which is normal) than HA. This is shown in Table 1, averaged over selected strains. For NA we estimated geographical scatter σ from Hawaii 2011. Here for HA we find systematic parallel motion of 〈ψMZ〉 and 〈ψKD〉 with peaks at Fort Dix (New Jersey 1976) and swine flu (2009), as shown in Figure 5. These correlate with the punctuations found in NA and have a natural interpretation as the HA analogs of the NA flu pandemics, which were explained in the NA paper. Thus we can estimate the HA intrinsic scatter by evaluating 〈ψMZ〉 and 〈ψKD〉 in a year where there was little activity (we used 1996) and using strains widely dispersed geographically.


Proteinquakes in the evolution of influenza virus hemagglutinin (A/H1N1) under opposing migration and vaccination pressures.

Phillips JC - Biomed Res Int (2015)

Sketch of chain A1 〈ψ(aa, 1)〉 evolution, with Fort Dix outbreak and swine flu peak (before vaccination program) indicated. The HA 〈ψ(aa, 1)〉 trends seen here parallel those for NA tabulated in [5].
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4309245&req=5

fig5: Sketch of chain A1 〈ψ(aa, 1)〉 evolution, with Fort Dix outbreak and swine flu peak (before vaccination program) indicated. The HA 〈ψ(aa, 1)〉 trends seen here parallel those for NA tabulated in [5].
Mentions: Perhaps the simplest difference between HA and NA profiles is the fact that NA profiles have overall ψMZ averages = 〈ψMZ〉 nearer 155 (hydroneutral, which is normal) than HA. This is shown in Table 1, averaged over selected strains. For NA we estimated geographical scatter σ from Hawaii 2011. Here for HA we find systematic parallel motion of 〈ψMZ〉 and 〈ψKD〉 with peaks at Fort Dix (New Jersey 1976) and swine flu (2009), as shown in Figure 5. These correlate with the punctuations found in NA and have a natural interpretation as the HA analogs of the NA flu pandemics, which were explained in the NA paper. Thus we can estimate the HA intrinsic scatter by evaluating 〈ψMZ〉 and 〈ψKD〉 in a year where there was little activity (we used 1996) and using strains widely dispersed geographically.

Bottom Line: Here we show that, while HA evolution is much more complex than NA evolution, it still shows abrupt punctuation changes linked to punctuation changes of NA.HA exhibits proteinquakes, which resemble earthquakes and are related to hydropathic shifting of sialic acid binding regions.Our comprehensive results present a historical (1945-2011) panorama of HA evolution over thousands of strains and are consistent with many studies of HA and NA interactions based on a few mutations of a few strains.

View Article: PubMed Central - PubMed

Affiliation: Department of Physics and Astronomy, Rutgers University, Piscataway, NJ 08854, USA.

ABSTRACT
Influenza virus contains two highly variable envelope glycoproteins, hemagglutinin (HA) and neuraminidase (NA). Here we show that, while HA evolution is much more complex than NA evolution, it still shows abrupt punctuation changes linked to punctuation changes of NA. HA exhibits proteinquakes, which resemble earthquakes and are related to hydropathic shifting of sialic acid binding regions. HA proteinquakes based on shifting sialic acid interactions are required for optimal balance between the receptor-binding and receptor-destroying activities of HA and NA for efficient virus replication. Our comprehensive results present a historical (1945-2011) panorama of HA evolution over thousands of strains and are consistent with many studies of HA and NA interactions based on a few mutations of a few strains.

Show MeSH
Related in: MedlinePlus