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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 〈ψ(j)111〉 chain profiles of four HA1 sequences, Netherlands 1954 (ADT78876), Fort Dix outbreak 1976 (ACU80014), postvaccination California 1978 (ABY81349, identical to Memphis 1983), and Texas 1986 (ABO44123), cut off at 266 (A1 chain only) to show more clearly mutational trends below 220. The Fort Dix outbreak increased hydrophobicity, especially below 150. After the 1976-77 vaccination program, in 1978–86 hydrophobicity dropped below the 1954 level in the region 120–230, spanning the two sialic acid binding sites determined crystallographically [7].
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fig3: The 〈ψ(j)111〉 chain profiles of four HA1 sequences, Netherlands 1954 (ADT78876), Fort Dix outbreak 1976 (ACU80014), postvaccination California 1978 (ABY81349, identical to Memphis 1983), and Texas 1986 (ABO44123), cut off at 266 (A1 chain only) to show more clearly mutational trends below 220. The Fort Dix outbreak increased hydrophobicity, especially below 150. After the 1976-77 vaccination program, in 1978–86 hydrophobicity dropped below the 1954 level in the region 120–230, spanning the two sialic acid binding sites determined crystallographically [7].

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 〈ψ(j)111〉 chain profiles of four HA1 sequences, Netherlands 1954 (ADT78876), Fort Dix outbreak 1976 (ACU80014), postvaccination California 1978 (ABY81349, identical to Memphis 1983), and Texas 1986 (ABO44123), cut off at 266 (A1 chain only) to show more clearly mutational trends below 220. The Fort Dix outbreak increased hydrophobicity, especially below 150. After the 1976-77 vaccination program, in 1978–86 hydrophobicity dropped below the 1954 level in the region 120–230, spanning the two sialic acid binding sites determined crystallographically [7].
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig3: The 〈ψ(j)111〉 chain profiles of four HA1 sequences, Netherlands 1954 (ADT78876), Fort Dix outbreak 1976 (ACU80014), postvaccination California 1978 (ABY81349, identical to Memphis 1983), and Texas 1986 (ABO44123), cut off at 266 (A1 chain only) to show more clearly mutational trends below 220. The Fort Dix outbreak increased hydrophobicity, especially below 150. After the 1976-77 vaccination program, in 1978–86 hydrophobicity dropped below the 1954 level in the region 120–230, spanning the two sialic acid binding sites determined crystallographically [7].
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