期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 105, 期 8, 页码 2800-2805出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0711963105
关键词
hemagglutinin; multivalency; sialylated glycans
资金
- NIGMS NIH HHS [GM57073, R01 GM057073, U54 GM062116, U54 GM62116, R37 GM057073] Funding Source: Medline
The human adaptation of influenza A viruses is critically governed by the binding specificity of the viral surface hemagglutinin (HA) to long (chain length) alpha 2-6 sialylated glycan (alpha 2-6) receptors on the human upper respiratory tissues. A recent study demonstrated that whereas the 1918 H1N1 pandemic virus, A/South Carolina/1/1918 (SC18), with alpha 2-6 binding preference transmitted efficiently, a single amino acid mutation on HIA resulted in a mixed alpha 2-3 sialylated glycan (alpha 2-3)/alpha 2-6 binding virus (NY18) that transmitted inefficiently. To define the biochemical basis for the observed differences in virus transmission, in this study, we have developed an approach to quantify the multivalent HA-glycan interactions. Analysis of the molecular HA-glycan contacts showed subtle changes resulting from the single amino acid variations between SC18 and NY18. The effect of these changes on glycan binding is amplified by multivalency, resulting in quantitative differences in their long alpha 2-6 glycan binding affinities. Furthermore, these differences are also reflected in the markedly distinct binding pattern of SC1 8 and NY18 HA to the physiological glycans present in human upper respiratory tissues. Thus, the dramatic lower binding affinity of NY18 to long alpha 2-6 glycans, as against a mixed alpha 2-3/6 binding, correlates with its inefficient transmission. In summary, this study establishes a quantitative biochemical correlate for influenza A virus transmission.
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