Escaping neutralization and gaining adaptation of highly pathogenic avian influenza (HPAI) H5N1 virus in interspecies evolution. (92.5)

Abstract

Abstract Limited amount of mutations in hemagglutinin (HA) of highly pathogenic avian influenza (HPAI) virus H5N1 would greatly facilitate cross-species transmission of avian influenza virus from birds to human. Neutralizing antibodies (nAbs) and receptor adaptation could drive interspecies transmission. In order to investigate the contemporaneous strain-specific and cross-strain nAb response against H5N1 pseudotype viruses and HA proteins, 10 human sera and 4 bird sera were collected to analyze their neutralization and binding activities using 4 H5N1 Has. Neutralization and binding activities of mAbs against QH and XJ H5N1 Has were observed. We found that some mutations appear in the outside of the receptor binding domain (RBD) of H5N1 hemagglutinin (HA), for example at aa 90 on QH H5N1 HA, which might induce a conformational change of the RBD to escape from nAb and change receptor preference simultaneously. These mutations were deemed as “key events” particularly during interspecies transmission to ensure the original invasion successful. They were the result of positive selection caused by antibodies. Some mutations in the RBD that only induce the change of receptor preference were deemed as “maintaining adaptation” to ensure influenza variants circulating in a new species. They were the result of adaptation caused by receptor. Our results suggest that continuing appearance of these two types of mutation made the variants persist in new species.