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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〉 HA1 chain profiles (55 < j < 311) of Genbank Brisbane ACB11812 (B) and Solomon Islands ACA33672 (A) [Hawaii 2007]. The key B-A mutations are K64I, MT (205, 206) KA, and N238D. The left-right difference crossover near 180 can be described as a hydropathic twist.
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fig4: The 〈ψ(j)111〉 HA1 chain profiles (55 < j < 311) of Genbank Brisbane ACB11812 (B) and Solomon Islands ACA33672 (A) [Hawaii 2007]. The key B-A mutations are K64I, MT (205, 206) KA, and N238D. The left-right difference crossover near 180 can be described as a hydropathic twist.

Mentions: The historical (1945-) directed evolution of roughnesses towards smaller values found for NA with W = 17 does not occur for HA. Instead, at each punctuation of NA, the HA chain hydroprofile 〈ψ(j)W〉 exhibits hydrophobic stabilization over selected blocks whose edges tend to coincide with one or both of the edges of the sialic acid binding site 130–230. Because this site is so wide, we have chosen to display hydroprofiles 〈ψ(j)W〉 with W = 111. To test this choice, we selected several HA sequences from Hawaii 2007. As was shown in [1], Hawaii 2007 consists mainly of two hydropathically recognizable subsets, one labeled “Brisbane,” and the other, “Solomon Islands.” The differences in their NA RMZ(17) are large (30% of the historical shift from strain A to strain D*) [1], while their HA RMZ(1) differences are only 1.5% of RMZ(1), which is only 2∑, where ∑ is the sum of the σ's of each subset [1]. From HA Hawaii 2007 we selected two sequences (ACB11812, Brisbane and ACA33672, Solomon Islands) with the largest BLAST nonpositive differences and the largest RMZ(1) differences. Their 〈ψ(j)111〉 chain profiles exhibit a striking sign difference reversal near 180, presumed to be associated with a change in sialic acid binding (Figure 4). A smaller window value of W = 75 shifts the crossover to below 180 and introduces secondary sign reversals, apparently associated with inadequate sliding window resolution (essentially Fresnel fringes associated with hydropathic waves at the sharp sialic acid edges). This shows that W = 111 is an excellent choice for HA1 sliding window width, as expected from its similarity to the length of the sialic acid binding site. An interesting point is that there is excellent correlation (87%) of R(111) for HA1 for the MZ and KD scales for the period 1918–2001, but this correlation breaks down with the advent of swine flu.


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〉 HA1 chain profiles (55 < j < 311) of Genbank Brisbane ACB11812 (B) and Solomon Islands ACA33672 (A) [Hawaii 2007]. The key B-A mutations are K64I, MT (205, 206) KA, and N238D. The left-right difference crossover near 180 can be described as a hydropathic twist.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: The 〈ψ(j)111〉 HA1 chain profiles (55 < j < 311) of Genbank Brisbane ACB11812 (B) and Solomon Islands ACA33672 (A) [Hawaii 2007]. The key B-A mutations are K64I, MT (205, 206) KA, and N238D. The left-right difference crossover near 180 can be described as a hydropathic twist.
Mentions: The historical (1945-) directed evolution of roughnesses towards smaller values found for NA with W = 17 does not occur for HA. Instead, at each punctuation of NA, the HA chain hydroprofile 〈ψ(j)W〉 exhibits hydrophobic stabilization over selected blocks whose edges tend to coincide with one or both of the edges of the sialic acid binding site 130–230. Because this site is so wide, we have chosen to display hydroprofiles 〈ψ(j)W〉 with W = 111. To test this choice, we selected several HA sequences from Hawaii 2007. As was shown in [1], Hawaii 2007 consists mainly of two hydropathically recognizable subsets, one labeled “Brisbane,” and the other, “Solomon Islands.” The differences in their NA RMZ(17) are large (30% of the historical shift from strain A to strain D*) [1], while their HA RMZ(1) differences are only 1.5% of RMZ(1), which is only 2∑, where ∑ is the sum of the σ's of each subset [1]. From HA Hawaii 2007 we selected two sequences (ACB11812, Brisbane and ACA33672, Solomon Islands) with the largest BLAST nonpositive differences and the largest RMZ(1) differences. Their 〈ψ(j)111〉 chain profiles exhibit a striking sign difference reversal near 180, presumed to be associated with a change in sialic acid binding (Figure 4). A smaller window value of W = 75 shifts the crossover to below 180 and introduces secondary sign reversals, apparently associated with inadequate sliding window resolution (essentially Fresnel fringes associated with hydropathic waves at the sharp sialic acid edges). This shows that W = 111 is an excellent choice for HA1 sliding window width, as expected from its similarity to the length of the sialic acid binding site. An interesting point is that there is excellent correlation (87%) of R(111) for HA1 for the MZ and KD scales for the period 1918–2001, but this correlation breaks down with the advent of swine flu.

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