Abstract
Influenza viruses continuously undergo antigenic changes with gradual accumulation of mutations in hemagglutinin (HA) that is a major determinant in subtype specificity. The identification of conserved epitopes within specific HA subtypes gives an important clue for developing new vaccines and diagnostics. We produced and characterized nine monoclonal antibodies that showed significant neutralizing activities against H1 subtype influenza viruses, and determined the complex structure of HA derived from a 2009 pandemic virus A/Korea/01/2009 (KR01) and the Fab fragment from H1-specific monoclonal antibody GC0587. The overall structure of the complex was essentially identical to the previously determined KR01 HA-Fab0757 complex structure. Both Fab0587 and Fab0757 recognize readily accessible head regions of HA, revealing broadly shared and conserved antigenic determinants among H1 subtypes. The β-strands constituted by Ser110-Glu115 and Lys169-Lys170 form H1 epitopes with distinct conformations from those of H1 and H3 HA sites. In particular, Glu112, Glu115, Lys169, and Lys171 that are highly conserved among H1 subtype HAs have close contacts with HCDR3 and LCDR3. The differences between Fab0587 and Fab0757 complexes reside mainly in HCDR3 and LCDR3, providing distinct antigenic determinants specific for 1918 pdm influenza strain. Our results demonstrate a potential key neutralizing epitope important for H1 subtype specificity in influenza virus.
Highlights
Influenza is a viral infectious disease of the respiratory tract that affects millions of people annually [1]
Our results demonstrate a potential key neutralizing epitope important for H1 subtype specificity in influenza virus
GC0587, GC0757 and GC1517 exhibited significant neutralizing activity against 2009 pdm H1N1 strains and a seasonal H1N1 strain, whereas GC0757, GC1517 and GC1761 showed the activity against A/Brevig Mission/1/1918
Summary
Influenza is a viral infectious disease of the respiratory tract that affects millions of people annually [1]. Combined with subsequent infection from bacterial pneumonia, influenza remains one of the leading causes of death in many countries [2]. The 1918 influenza pandemic (pdm) killed 40–50 million people worldwide [3] and the pdm influenza that was identified in 214 countries caused more than 18,000 deaths worldwide, despite global influenza preparedness [4]. Influenza viruses which belong to the family of Orthomyxoviridae have three antigenically distinct types of virus, A, B, and C [5,6]. After the recent discovery of a new subtype virus genome identified from bat, there are currently 17
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