Conformational intermediates and fusion activity of influenza virus hemagglutinin.
Three strains of influenza virus (H1, H2, and H3) exhibited similar characteristics in the ability of their hemagglutinin (HA) to induce membrane fusion, but the HAs differed in their susceptibility to inactivation. The extent of inactivation depended on the pH of preincubation and was lowest for A/Japan (H2 subtype), in agreement with previous studies (A. Puri, F. Booy, R. W. Doms, J. M. White, and R. Blumenthal, J. Virol. 64:3824-3832, 1990). While significant inactivation of X31 (H3 subtype) was observed at 37 degrees C at pH values corresponding to the maximum of fusion (about pH 5.0), no inactivation was seen at preincubation pH values 0.2 to 0.4 pH units higher. Surprisingly, low-pH preincubation under those conditions enhanced the fusion rates and extents of A/Japan as well as those of X31. For A/PR 8/34 (H1 subtype), neither a shift of the pH (to >5.0) nor a decrease of the temperature to 20 degrees C was sufficient to prevent inactivation. We provide evidence that the activated HA is a conformational intermediate distinct from the native structure and from the final structure associated with the conformational change of HA, which is implicated by the high-resolution structure of the soluble trimeric fragment TBHA2 (P. A. Bullough, F. M. Hughson, J. J. Skehel, and D. C. Wiley, Nature 371:37-43, 1994).
Korte
T
T
Laboratory of Experimental and Computational Biology, National Cancer Institute-Frederick Cancer Research & Development Center, National Institutes of Health, Frederick, Maryland 21702, USA.
Ludwig
K
K
Booy
F P
FP
Blumenthal
R
R
Herrmann
A
A
D000817:Anilino Naphthalenesulfonates / Q000378:metabolism; D005453:Fluorescence; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D009980:Influenza A virus / Q000502:physiology; D008561:Membrane Fusion; D011487:Protein Conformation; D013696:Temperature
D000817:Anilino Naphthalenesulfonates; D019267:Hemagglutinin Glycoproteins, Influenza Virus; C035763:5,5'-bis(8-(phenylamino)-1-naphthalenesulfonate)