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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

Broad trends in W = 111 roughnesses for (a) HA1 and (b) NA. Data primarily from Memphis.
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Related In: Results  -  Collection


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fig11: Broad trends in W = 111 roughnesses for (a) HA1 and (b) NA. Data primarily from Memphis.

Mentions: Could HA W = 111 block hydropathic roughnesses have a secondary effect on NA at W = 111? This question is addressed in Figure 11, with data restricted to Memphis. We see in (a) a broad downward trend in HA1 with two peaks in 1983 and 2000, but these either follow the 1976 W = 17 NA peak or precede the 2007 swine flu peak. In other words, HA evolution may be coupled to NA evolution but not in a simple way. This point is brought out in (b), which shows only one peak, placed between the two HA peaks. There appears to be some measure of complementarity of HA and NA evolution on the sialidase W = 111 scale. Overall we recognize that H1N1 HA and NA evolution is dominated by at most two length scales associated with N-glycans and sialic acid. Because our analysis is hierarchical (it distinguishes between increasing and decreasing roughness) and includes detailed quantitative aspects of sequence evolution on large length scales not accessible to similarity analysis, it could be useful in refining binding data [5, 21]. Our method is effective over long length scales not accessed by methods used to study short synthetic peptides [22].


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

Phillips JC - Biomed Res Int (2015)

Broad trends in W = 111 roughnesses for (a) HA1 and (b) NA. Data primarily from Memphis.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig11: Broad trends in W = 111 roughnesses for (a) HA1 and (b) NA. Data primarily from Memphis.
Mentions: Could HA W = 111 block hydropathic roughnesses have a secondary effect on NA at W = 111? This question is addressed in Figure 11, with data restricted to Memphis. We see in (a) a broad downward trend in HA1 with two peaks in 1983 and 2000, but these either follow the 1976 W = 17 NA peak or precede the 2007 swine flu peak. In other words, HA evolution may be coupled to NA evolution but not in a simple way. This point is brought out in (b), which shows only one peak, placed between the two HA peaks. There appears to be some measure of complementarity of HA and NA evolution on the sialidase W = 111 scale. Overall we recognize that H1N1 HA and NA evolution is dominated by at most two length scales associated with N-glycans and sialic acid. Because our analysis is hierarchical (it distinguishes between increasing and decreasing roughness) and includes detailed quantitative aspects of sequence evolution on large length scales not accessible to similarity analysis, it could be useful in refining binding data [5, 21]. Our method is effective over long length scales not accessed by methods used to study short synthetic peptides [22].

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