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Quantitative biochemical rationale for differences in transmissibility of 1918 pandemic influenza A viruses.

ABSTRACT: The human adaptation of influenza A viruses is critically governed by the binding specificity of the viral surface hemagglutinin (HA) to long (chain length) alpha2-6 sialylated glycan (alpha2-6) 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 alpha2-6 binding preference transmitted efficiently, a single amino acid mutation on HA resulted in a mixed alpha2-3 sialylated glycan (alpha2-3)/alpha2-6 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 alpha2-6 glycan binding affinities. Furthermore, these differences are also reflected in the markedly distinct binding pattern of SC18 and NY18 HA to the physiological glycans present in human upper respiratory tissues. Thus, the dramatic lower binding affinity of NY18 to long alpha2-6 glycans, as against a mixed alpha2-3/6 binding, correlates with its inefficient transmission. In summary, this study establishes a quantitative biochemical correlate for influenza A virus transmission.

SUBMITTER: Srinivasan A

PROVIDER: S-EPMC2268540 | biostudies-literature | 2008 Feb

REPOSITORIES: biostudies-literature

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Quantitative biochemical rationale for differences in transmissibility of 1918 pandemic influenza A viruses.

Srinivasan Aravind A Viswanathan Karthik K Raman Rahul R Chandrasekaran Aarthi A Raguram S S Tumpey Terrence M TM Sasisekharan V V Sasisekharan Ram R

Proceedings of the National Academy of Sciences of the United States of America 20080219 8

The human adaptation of influenza A viruses is critically governed by the binding specificity of the viral surface hemagglutinin (HA) to long (chain length) alpha2-6 sialylated glycan (alpha2-6) 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 alpha2-6 binding preference transmitted efficiently, a single amino acid mutation on HA resulted in a mixed alpha2-3 sialylated glycan (alpha2-3)/a ...[more]

PMID: 18287068

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Project description:BACKGROUND:Increasing our knowledge of past influenza pandemic patterns in different regions of the world is crucial to guide preparedness plans against future influenza pandemics. Here, we undertook extensive archival collection efforts from three representative cities of Peru-Lima in the central coast, Iquitos in the northeastern Amazon region, Ica in the southern coast-to characterize the temporal, age and geographic patterns of the 1918-1920 influenza pandemic in this country. MATERIALS AND METHODS:We analyzed historical documents describing the 1918-1920 influenza pandemic in Peru and retrieved individual mortality records from local provincial archives for quantitative analysis. We applied seasonal excess mortality models to daily and monthly respiratory mortality rates for 1917-1920 and quantified transmissibility estimates based on the daily growth rate in respiratory deaths. RESULTS:A total of 52,739 individual mortality records were inspected from local provincial archives. We found evidence for an initial mild pandemic wave during July-September 1918 in Lima, identified a synchronized severe pandemic wave of respiratory mortality in all three locations during November 1918-February 1919, and a severe pandemic wave during January 1920-March 1920 in Lima and July-October 1920 in Ica. There was no recrudescent pandemic wave in 1920 in Iquitos. Remarkably, Lima experienced the brunt of the 1918-1920 excess mortality impact during the 1920 recrudescent wave, with all age groups experiencing an increase in all cause excess mortality from 1918-1919 to 1920. Middle age groups experienced the highest excess mortality impact, relative to baseline levels, in the 1918-1919 and 1920 pandemic waves. Cumulative excess mortality rates for the 1918-1920 pandemic period were higher in Iquitos (2.9%) than Lima (1.6%). The mean reproduction number for Lima was estimated in the range 1.3-1.5. CONCLUSIONS:We identified synchronized pandemic waves of intense excess respiratory mortality during November 1918-February 1919 in Lima, Iquitos, Ica, followed by asynchronous recrudescent waves in 1920. Cumulative data from quantitative studies of the 1918 influenza pandemic in Latin American settings have confirmed the high mortality impact associated with this pandemic. Further historical studies in lesser studied regions of Latin America, Africa, and Asia are warranted for a full understanding of the global impact of the 1918 pandemic virus.

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Quantitative biochemical rationale for differences in transmissibility of 1918 pandemic influenza A viruses.

Publications

Quantitative biochemical rationale for differences in transmissibility of 1918 pandemic influenza A viruses.

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