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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.

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Related in: MedlinePlus

The full 〈ψ(j)111〉 chain profiles of three HA sequences, Netherlands 1954, Fort Dix outbreak (1976), and postvaccination California 1978. The cleavage site separates HA1 from HA2. Mutations occur primarily in the HA1 region below 300. Note that the “highly conserved H1 subtype-specific epitope” [6] 58–72 became strongly hydrophobic in the Fort Dix outbreak. The epitope covering 108–122 [6] includes the spectacular Fort Dix peak near site 117. Studies with the epitope covering 108–122 of mice infected with the three strains shown here would be well worth further effort.
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fig2: The full 〈ψ(j)111〉 chain profiles of three HA sequences, Netherlands 1954, Fort Dix outbreak (1976), and postvaccination California 1978. The cleavage site separates HA1 from HA2. Mutations occur primarily in the HA1 region below 300. Note that the “highly conserved H1 subtype-specific epitope” [6] 58–72 became strongly hydrophobic in the Fort Dix outbreak. The epitope covering 108–122 [6] includes the spectacular Fort Dix peak near site 117. Studies with the epitope covering 108–122 of mice infected with the three strains shown here would be well worth further effort.

Mentions: The 565 amino acids of compacted HA exhibit a rich Euclidean structure composed of two chains, HA1 and HA2 [9]. The two ends of the globularly combined chains are stabilized by hydrophobic peaks, and there is a third peak near 310 stabilizing the center of HA. See Figure 2, which exhibits changes in the hydropathic chain profile using the MZ scale [4] averaged over a long sliding window length W = 111; this choice of W will be discussed below. The various evolutionary punctuations of companion NA sequences [1] will be examined here for HA (Figure 2 shows one of them, the 1976 Fort Dix outbreak, accompanied by a hasty vaccination program.) The central third 310 hydrophobic peak occurs on the HA1 side of the 343 cleavage site. It stabilizes HA1 after the fusion segment 345–367 of HA2 merged with the target membrane. As in Figure 3 almost all the evolutionary changes occur in HA1 1–300, and this is the region discussed here in detail (see Figure 3). It is dominated by the globular head domain, which includes the sialic acid binding site 130–230 and a number of glycosylation sites, which have increased since 1918 [9].


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

Phillips JC - Biomed Res Int (2015)

The full 〈ψ(j)111〉 chain profiles of three HA sequences, Netherlands 1954, Fort Dix outbreak (1976), and postvaccination California 1978. The cleavage site separates HA1 from HA2. Mutations occur primarily in the HA1 region below 300. Note that the “highly conserved H1 subtype-specific epitope” [6] 58–72 became strongly hydrophobic in the Fort Dix outbreak. The epitope covering 108–122 [6] includes the spectacular Fort Dix peak near site 117. Studies with the epitope covering 108–122 of mice infected with the three strains shown here would be well worth further effort.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: The full 〈ψ(j)111〉 chain profiles of three HA sequences, Netherlands 1954, Fort Dix outbreak (1976), and postvaccination California 1978. The cleavage site separates HA1 from HA2. Mutations occur primarily in the HA1 region below 300. Note that the “highly conserved H1 subtype-specific epitope” [6] 58–72 became strongly hydrophobic in the Fort Dix outbreak. The epitope covering 108–122 [6] includes the spectacular Fort Dix peak near site 117. Studies with the epitope covering 108–122 of mice infected with the three strains shown here would be well worth further effort.
Mentions: The 565 amino acids of compacted HA exhibit a rich Euclidean structure composed of two chains, HA1 and HA2 [9]. The two ends of the globularly combined chains are stabilized by hydrophobic peaks, and there is a third peak near 310 stabilizing the center of HA. See Figure 2, which exhibits changes in the hydropathic chain profile using the MZ scale [4] averaged over a long sliding window length W = 111; this choice of W will be discussed below. The various evolutionary punctuations of companion NA sequences [1] will be examined here for HA (Figure 2 shows one of them, the 1976 Fort Dix outbreak, accompanied by a hasty vaccination program.) The central third 310 hydrophobic peak occurs on the HA1 side of the 343 cleavage site. It stabilizes HA1 after the fusion segment 345–367 of HA2 merged with the target membrane. As in Figure 3 almost all the evolutionary changes occur in HA1 1–300, and this is the region discussed here in detail (see Figure 3). It is dominated by the globular head domain, which includes the sialic acid binding site 130–230 and a number of glycosylation sites, which have increased since 1918 [9].

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