RRC ID 81295
Author Sekine W, Kamiki H, Ishida H, Matsugo H, Ohira K, Li K, Katayama M, Takenaka-Uema A, Murakami S, Horimoto T.
Title Adaptation potential of H3N8 canine influenza virus in human respiratory cells.
Journal Sci Rep
Abstract In 2004, the equine-origin H3N8 canine influenza virus (CIV) first caused an outbreak with lethal cases in racing greyhounds in Florida, USA, and then spread to domestic dogs nationwide. Although transmission of this canine virus to humans has not been reported, it is important to evaluate its zoonotic potential because of the high contact opportunities between companion dogs and humans. To gain insight into the interspecies transmissibility of H3N8 CIV, we tested its adaptability to human respiratory A549 cells through successive passages. We found that CIV acquired high growth properties in these cells mainly through mutations in surface glycoproteins, such as hemagglutinin (HA) and neuraminidase (NA). Our reverse genetics approach revealed that HA2-K82E, HA2-R163K, and NA-S18L mutations were responsible for the increased growth of CIV in human cells. Molecular analyses revealed that both HA2 mutations altered the optimum pH for HA membrane fusion activity and that the NA mutation changed the HA-NA functional balance. These findings suggest that H3N8 CIV could evolve into a human pathogen with pandemic potential through a small number of mutations, thereby posing a threat to public health in the future.
Volume 14(1)
Pages 18750
Published 2024-8-13
DOI 10.1038/s41598-024-69509-x
PII 10.1038/s41598-024-69509-x
PMID 39138310
PMC PMC11322661
MeSH A549 Cells Adaptation, Physiological / genetics Animals Dogs Hemagglutinin Glycoproteins, Influenza Virus / genetics Hemagglutinin Glycoproteins, Influenza Virus / metabolism Humans Influenza A Virus, H3N8 Subtype* / genetics Influenza A Virus, H3N8 Subtype* / physiology Influenza, Human / transmission Influenza, Human / virology Mutation* Neuraminidase* / genetics Neuraminidase* / metabolism Orthomyxoviridae Infections / transmission Orthomyxoviridae Infections / virology
Resource
Human and Animal Cells 293T(RCB2202)