Impact of Mutations in the Hemagglutinin of H10N7 Viruses Isolated from Seals on Virus Replication in Avian and Human Cells
| Autor: | Jutta Veits, Anne Dittrich, Ahmed H. Salaheldin, Thomas C Mettenleiter, Marcel Gischke, Elsayed M. Abdelwhab, David Scheibner |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Models Molecular Protein Conformation viruses receptor binding lcsh:QR1-502 Hemagglutinin Glycoproteins Influenza Virus adaptation Chick Embryo medicine.disease_cause Virus Replication lcsh:Microbiology law.invention law Prevalence Receptor Influenza A Virus H10N7 Subtype harbor seals Recombination Genetic poultry Infectious Diseases Recombinant DNA influenza Protein subunit 030106 microbiology interspecies transmission Genome Viral Phoca Biology Virus Article Cell Line 03 medical and health sciences Orthomyxoviridae Infections Virology Influenza Human medicine Animals Humans H10N7 Influenza A virus subtype H5N1 In vitro Reverse genetics 030104 developmental biology Viral replication Influenza in Birds Mutation Chickens |
| Zdroj: | Viruses Viruses; Volume 10; Issue 2; Pages: 83 Viruses, Vol 10, Iss 2, p 83 (2018) |
| ISSN: | 1999-4915 |
| Popis: | Wild birds are the reservoir for low-pathogenic avian influenza viruses, which are frequently transmitted to domestic birds and occasionally to mammals. In 2014, an H10N7 virus caused severe mortality in harbor seals in northeastern Europe. Although the hemagglutinin (HA) of this virus was closely related to H10 of avian H10N4 virus, it possessed unique nonsynonymous mutations, particularly in the HA1 subunit in or adjacent to the receptor binding domain and proteolytic cleavage site. Here, the impact of these mutations on virus replication was studied in vitro. Using reverse genetics, an avian H10N4 virus was cloned, and nine recombinant viruses carrying one of eight unique mutations or the complete HA from the seal virus were rescued. Receptor binding affinity, replication in avian and mammalian cell cultures, cell-to-cell spread, and HA cleavability of these recombinant viruses were studied. Results show that wild-type recombinant H10N4 virus has high affinity to avian-type sialic acid receptors and no affinity to mammalian-type receptors. The H10N7 virus exhibits dual receptor binding affinity. Interestingly, Q220L (H10 numbering) in the rim of the receptor binding pocket increased the affinity of the H10N4 virus to mammal-type receptors and completely abolished the affinity to avian-type receptors. No remarkable differences in cell-to-cell spread or HA cleavability were observed. All viruses, including the wild-type H10N7 virus, replicated at higher levels in chicken cells than in human cells. These results indicate that H10N7 acquired adaptive mutations (e.g., Q220L) to enhance replication in mammals and retained replication efficiency in the original avian host. |
| Databáze: | OpenAIRE |
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