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National Institute of General Medical Sciences (NIGMS) and National Cancer Institute (NCI) of the National Institutes of Health (NIH)
 

"Swine flu" virus similar to 1918 "Spanish flu" virus

Ian Wilson group (The Scripps Research Institute) and collaborators

 

Ian Wilson's group determined structures of antigenically important hemagglutinins (HA) related to the 2009 H1N1 influenza virus responsible for the "swine flu" pandemic. Pandemics generally occur when a virus from birds or pigs becomes infectious to humans and introduces a new HA sub-type to a vulnerable human population. This differs from the seasonal flu, where flu viruses circulating in the human population gradually acquire mutations. The 2009 "swine flu" is the first characterized pandemic in which a HA sub-type is related, albeit distantly, to a currently circulating HA sub-type. The structural work helps explain why the 2009 "swine flu" disproportionately affects children and young adults. Like other HAs, the 2009 H1N1 HA (determined with data from SSRL) has a long, extended stem region and a membrane-distal globular cap. Remarkably, the epitope-rich cap region of the 2009 HA is similar to the cap region of the HA from the virus responsible for the catastrophic 1918 "Spanish flu". An antibody, 2D1, from an elderly survivor of the 1918 pandemic was cross-neutralizing to HA from both the 1918 virus and to the 2009 virus. Solved with data from GM/CA beamline 23ID-B, the structure of a 1918 H1N1 HA in complex with the 2D1 Fab helped explain in detail why this antibody has a strong affinity for both the 1918 and 2009 pandemic viruses but less affinity for recent seasonal flu viruses and why individuals old enough to have antibodies to the 1918 virus and its descendents are less vulnerable to "swine flu" than are younger people.

Figure: Structure of cross-neutralizing antibody 2D1 in complex with the 1918 Influenza virus hemagglutinin [ PDB ID 3LZF ]

 

Citation:
Xu, R, Ekiert, DC, Krause, JC, Hai, R, Crowe, JE, Jr., Wilson, IA. Structural Basis of Preexisting Immunity to the 2009 H1N1 Pandemic Influenza Virus, Science 328, 357-360 (2010). DOI: 10.1126/science.1186430 (2011).


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