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) |