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...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
MDPI AG
2022-05-01
|
Series: | Viruses |
Subjects: | |
Online Access: | https://www.mdpi.com/1999-4915/14/5/1091 |
_version_ | 1797494510755774464 |
---|---|
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. |
first_indexed | 2024-03-10T01:35:21Z |
format | Article |
id | doaj.art-3d4a967b262d4774b1bd615d46474040 |
institution | Directory Open Access Journal |
issn | 1999-4915 |
language | English |
last_indexed | 2024-03-10T01:35:21Z |
publishDate | 2022-05-01 |
publisher | MDPI AG |
record_format | Article |
series | Viruses |
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 |
work_keys_str_mv | AT watarusekine adaptationoftheh7n2felineinfluenzavirustohumanrespiratorycellculture AT akikotakenakauema adaptationoftheh7n2felineinfluenzavirustohumanrespiratorycellculture AT haruhikokamiki adaptationoftheh7n2felineinfluenzavirustohumanrespiratorycellculture AT hirohoishida adaptationoftheh7n2felineinfluenzavirustohumanrespiratorycellculture AT hiromichimatsugo adaptationoftheh7n2felineinfluenzavirustohumanrespiratorycellculture AT shinmurakami adaptationoftheh7n2felineinfluenzavirustohumanrespiratorycellculture AT taisukehorimoto adaptationoftheh7n2felineinfluenzavirustohumanrespiratorycellculture |