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0rganization of Influenza A virus envelope at neutral and low pH

¹ Institut National de la Santé et de la Recherche Médicale, Unité 554;
² Sanofi PASTEUR;
³ Centre National de la Recherche Scientifique, UMR 5048

⁴ E-mail: clg{at}cbs.cnrs.fr

Fusion of the Influenza A H1N1 virus envelope with endosomal membrane at low pH allows the intracellular delivery of the viral genome playing an essential role in the infection process. Low pH induces an irreversible modification of the virus envelope which has so far resisted to 3D structural analysis, partly due to virus pleiomorphy. Here we show that atomic force microscopy (AFM) in physiological buffer can image structural details of the virus envelope both at neutral pH and after a low pH treatment. At low and intermediate magnification, AFM of control virions confirms both the pleiomorphy and the existence of zones devoid of glycoprotein spikes at the virus surface established by electron microscopy. At higher magnification, the unique vertical resolution of the AFM in 3D topography demonstrates the lateral heterogeneity in spikes distribution and strongly suggests that, at least locally, they can be organized in an irregular honeycomb pattern. The surface honeycomb pattern was more easily detected due to an increase in spikes height following low pH treatment at low temperature which likely prevented disruption of the organization. This enhanced contrast associated with low pH treatment emphasizes differences in the glycoprotein distribution between virions. It is concluded that, in association with EM approaches, AFM can help to establish correlation between surface structure and Influenza virus infectivity/pathogenicity.

Received 17 July 2009; accepted 13 October 2009.