title: Aptamers that bind to the hemagglutinin of the recent pandemic influenza virus H1N1 and efficiently inhibit agglutination.
abstract: Influenza virus hemagglutinin (HA) mediates both receptor (glycan) binding and membrane fusion for cell entry and has been the basis for typing influenza A viruses. In this study we have selected RNA aptamers (D-12 and D-26) that specifically target the HA protein of the recent pandemic influenza virus pdmH1N1 (A/California/07/2009). Among the selected aptamers the D-26 aptamer showed higher affinity for the HA of pdmH1N1 and was able to distinguish HA derived from other sub-types of influenza A viruses. The affinity of the D-26 aptamer was further improved upon incorporation of 2'-fluoropyrimidines to a level of 67 fM. Furthermore, the high affinity D-12 and D-26 aptamers were tested for their ability to interfere with HA-glycan interactions using a chicken red blood cell (RBC) agglutination assay. At a concentration of 200 nM the D-26 aptamer completely abolished the agglutination of RBCs, whereas D-12 only did so at 400 nM. These studies suggest that the selected aptamer D-26 not only has a higher affinity and specificity for the HA of pdmH1N1 but also has a better ability to efficiently interfere with HA-glycan interactions compared with the D-12 aptamer. The D-26 aptamer warrants further study regarding its application in developing topical virucidal products against the pdmH1N1 virus and also in surveillance of the pdmH1N1 influenza virus.
authors.affiliation: RNA Processing Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Central 6, 1-1-1 Higashi, Tsukuba City 305-8566, Ibaraki, Japan; Nanoelectronics Research Centre, National Institute of Advanced Industrial Science and Technology, 1-1-1 Higashi, Tsukuba City 305-8566, Ibaraki, Japan.
authors.forename: Subash C B
authors.initials: SC
authors.lastname: Gopinath
authors.forename: Penmetcha K R
authors.initials: PK
authors.lastname: Kumar
mesh_terms: D000371:Agglutination; D000372:Agglutination Tests; D000818:Animals; D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D002645:Chickens; D004722:Endoribonucleases / Q000378:metabolism; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000302:isolation & purification / Q000378:metabolism*; D058507:Host Specificity; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000378:metabolism*; D007251:Influenza, Human / Q000453:epidemiology / Q000821:virology; D007700:Kinetics; D008024:Ligands; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009976:Orthomyxoviridae Infections / Q000821:virology; D058873:Pandemics; D011134:Polysaccharides / Q000378:metabolism; D011485:Protein Binding; D020871:RNA Stability
chemical_list: D052157:Aptamers, Nucleotide; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D008024:Ligands; D011134:Polysaccharides; D004722:Endoribonucleases; D019158:N-Acetylneuraminic Acid
keywords: Agglutination; Aptamer; Hemagglutinin; Influenza; Pandemic