Adaptation of the H7N2 Feline Influenza Virus to Human Respiratory Cell Culture

During 2016–2017, the H7N2 feline influenza virus infected more than 500 cats in animal shelters in New York, USA. A veterinarian who had treated the cats became infected with this feline virus and showed mild respiratory symptoms. This suggests that the H7N2 feline influenza virus may evolve into a...

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Main Authors: Wataru Sekine, Akiko Takenaka-Uema, Haruhiko Kamiki, Hiroho Ishida, Hiromichi Matsugo, Shin Murakami, Taisuke Horimoto
Format: Article
Language:English
Published: MDPI AG 2022-05-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/14/5/1091
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author Wataru Sekine
Akiko Takenaka-Uema
Haruhiko Kamiki
Hiroho Ishida
Hiromichi Matsugo
Shin Murakami
Taisuke Horimoto
author_facet Wataru Sekine
Akiko Takenaka-Uema
Haruhiko Kamiki
Hiroho Ishida
Hiromichi Matsugo
Shin Murakami
Taisuke Horimoto
author_sort Wataru Sekine
collection DOAJ
description During 2016–2017, the H7N2 feline influenza virus infected more than 500 cats in animal shelters in New York, USA. A veterinarian who had treated the cats became infected with this feline virus and showed mild respiratory symptoms. This suggests that the H7N2 feline influenza virus may evolve into a novel pandemic virus with a high pathogenicity and transmissibility as a result of mutations in humans. In this study, to gain insight into the molecular basis of the transmission of the feline virus to humans, we selected mutant viruses with enhanced growth in human respiratory A549 cells via successive passages of the virus and found almost all mutations to be in the envelope glycoproteins, such as hemagglutinin (HA) and neuraminidase (NA). The reverse genetics approach revealed that the HA mutations, HA1-H16Q, HA2-I47T, or HA2-Y119H, in the stalk region can lead to a high growth of mutant viruses in A549 cells, possibly by changing the pH threshold for membrane fusion. Furthermore, NA mutation, I28S/L, or three-amino-acid deletion in the transmembrane region can enhance viral growth in A549 cells, possibly by changing the HA–NA functional balance. These findings suggest that the H7N2 feline influenza virus has the potential to become a human pathogen by adapting to human respiratory cells, owing to the synergistic biological effect of the mutations in its envelope glycoproteins.
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spelling doaj.art-3d4a967b262d4774b1bd615d464740402023-11-23T13:33:10ZengMDPI AGViruses1999-49152022-05-01145109110.3390/v14051091Adaptation of the H7N2 Feline Influenza Virus to Human Respiratory Cell CultureWataru Sekine0Akiko Takenaka-Uema1Haruhiko Kamiki2Hiroho Ishida3Hiromichi Matsugo4Shin Murakami5Taisuke Horimoto6Laboratory of Veterinary Microbiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, JapanLaboratory of Veterinary Microbiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, JapanLaboratory of Veterinary Microbiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, JapanLaboratory of Veterinary Microbiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, JapanLaboratory of Veterinary Microbiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, JapanLaboratory of Veterinary Microbiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, JapanLaboratory of Veterinary Microbiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, JapanDuring 2016–2017, the H7N2 feline influenza virus infected more than 500 cats in animal shelters in New York, USA. A veterinarian who had treated the cats became infected with this feline virus and showed mild respiratory symptoms. This suggests that the H7N2 feline influenza virus may evolve into a novel pandemic virus with a high pathogenicity and transmissibility as a result of mutations in humans. In this study, to gain insight into the molecular basis of the transmission of the feline virus to humans, we selected mutant viruses with enhanced growth in human respiratory A549 cells via successive passages of the virus and found almost all mutations to be in the envelope glycoproteins, such as hemagglutinin (HA) and neuraminidase (NA). The reverse genetics approach revealed that the HA mutations, HA1-H16Q, HA2-I47T, or HA2-Y119H, in the stalk region can lead to a high growth of mutant viruses in A549 cells, possibly by changing the pH threshold for membrane fusion. Furthermore, NA mutation, I28S/L, or three-amino-acid deletion in the transmembrane region can enhance viral growth in A549 cells, possibly by changing the HA–NA functional balance. These findings suggest that the H7N2 feline influenza virus has the potential to become a human pathogen by adapting to human respiratory cells, owing to the synergistic biological effect of the mutations in its envelope glycoproteins.https://www.mdpi.com/1999-4915/14/5/1091feline influenzaH7N2hemagglutininneuraminidasemutationadaptation
spellingShingle Wataru Sekine
Akiko Takenaka-Uema
Haruhiko Kamiki
Hiroho Ishida
Hiromichi Matsugo
Shin Murakami
Taisuke Horimoto
Adaptation of the H7N2 Feline Influenza Virus to Human Respiratory Cell Culture
Viruses
feline influenza
H7N2
hemagglutinin
neuraminidase
mutation
adaptation
title Adaptation of the H7N2 Feline Influenza Virus to Human Respiratory Cell Culture
title_full Adaptation of the H7N2 Feline Influenza Virus to Human Respiratory Cell Culture
title_fullStr Adaptation of the H7N2 Feline Influenza Virus to Human Respiratory Cell Culture
title_full_unstemmed Adaptation of the H7N2 Feline Influenza Virus to Human Respiratory Cell Culture
title_short Adaptation of the H7N2 Feline Influenza Virus to Human Respiratory Cell Culture
title_sort adaptation of the h7n2 feline influenza virus to human respiratory cell culture
topic feline influenza
H7N2
hemagglutinin
neuraminidase
mutation
adaptation
url https://www.mdpi.com/1999-4915/14/5/1091
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