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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

HA (1–565) is structurally separated into head HA1 (18–342) and stalk HA2 (344–565) parts, the latter being attached to the membrane. The head hydroprofiles of the two historic HA strains, Fort Dix 1976 (Genbank ACU80014) and Puerto Rico 1934 (P03452), are compared with a modern (vaccination moderated) strain, New York ACQ84467. The origin of the severity of the 1976 Fort Dix strain is explained by its strongly hydrophobic head amino acid content, especially near site 110. The advent of swine flu (2001–2007) and the response (2009–2011) to its vaccination program flattened (smoothed) current strains (like New York 2009) and reduced their virulence.
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fig1: HA (1–565) is structurally separated into head HA1 (18–342) and stalk HA2 (344–565) parts, the latter being attached to the membrane. The head hydroprofiles of the two historic HA strains, Fort Dix 1976 (Genbank ACU80014) and Puerto Rico 1934 (P03452), are compared with a modern (vaccination moderated) strain, New York ACQ84467. The origin of the severity of the 1976 Fort Dix strain is explained by its strongly hydrophobic head amino acid content, especially near site 110. The advent of swine flu (2001–2007) and the response (2009–2011) to its vaccination program flattened (smoothed) current strains (like New York 2009) and reduced their virulence.

Mentions: As noted in [1], most of the evolutionary changes in HA occur in the head chain HA1 (18–342) denoted by HA1. As discussed in more detail below, these changes are best displayed with hydropathic chain profiles using the MZ scale [4] averaged over a long sliding window length W = 111. On an historic scale, going back to the 1918 pandemic, these HA1 changes are large and dramatic, as shown in Figure 1.


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

Phillips JC - Biomed Res Int (2015)

HA (1–565) is structurally separated into head HA1 (18–342) and stalk HA2 (344–565) parts, the latter being attached to the membrane. The head hydroprofiles of the two historic HA strains, Fort Dix 1976 (Genbank ACU80014) and Puerto Rico 1934 (P03452), are compared with a modern (vaccination moderated) strain, New York ACQ84467. The origin of the severity of the 1976 Fort Dix strain is explained by its strongly hydrophobic head amino acid content, especially near site 110. The advent of swine flu (2001–2007) and the response (2009–2011) to its vaccination program flattened (smoothed) current strains (like New York 2009) and reduced their virulence.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: HA (1–565) is structurally separated into head HA1 (18–342) and stalk HA2 (344–565) parts, the latter being attached to the membrane. The head hydroprofiles of the two historic HA strains, Fort Dix 1976 (Genbank ACU80014) and Puerto Rico 1934 (P03452), are compared with a modern (vaccination moderated) strain, New York ACQ84467. The origin of the severity of the 1976 Fort Dix strain is explained by its strongly hydrophobic head amino acid content, especially near site 110. The advent of swine flu (2001–2007) and the response (2009–2011) to its vaccination program flattened (smoothed) current strains (like New York 2009) and reduced their virulence.
Mentions: As noted in [1], most of the evolutionary changes in HA occur in the head chain HA1 (18–342) denoted by HA1. As discussed in more detail below, these changes are best displayed with hydropathic chain profiles using the MZ scale [4] averaged over a long sliding window length W = 111. On an historic scale, going back to the 1918 pandemic, these HA1 changes are large and dramatic, as shown in Figure 1.

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