The replication of Bangladeshi H9N2 avian influenza viruses carrying genes from H7N3 in mammals.
H9N2 avian influenza viruses are continuously monitored by the World Health Organization because they are endemic; they continually reassort with H5N1, H7N9 and H10N8 viruses; and they periodically cause human infections. We characterized H9N2 influenza viruses carrying internal genes from highly pathogenic H7N3 viruses, which were isolated from chickens or quail from live-bird markets in Bangladesh between 2010 and 2013. All of the H9N2 viruses used in this study carried mammalian host-specific mutations. We studied their replication kinetics in normal human bronchoepithelial cells and swine tracheal and lung explants, which exhibit many features of the mammalian airway epithelium and serve as a mammalian host model. All H9N2 viruses replicated to moderate-to-high titers in the normal human bronchoepithelial cells and swine lung explants, but replication was limited in the swine tracheal explants. In Balb/c mice, the H9N2 viruses were nonlethal, replicated to moderately high titers and the infection was confined to the lungs. In the ferret model of human influenza infection and transmission, H9N2 viruses possessing the Q226L substitution in hemagglutinin replicated well without clinical signs and spread via direct contact but not by aerosol. None of the H9N2 viruses tested were resistant to the neuraminidase inhibitors. Our study shows that the Bangladeshi H9N2 viruses have the potential to infect humans and highlights the importance of monitoring and characterizing this influenza subtype to better understand the potential risk these viruses pose to humans.
Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Karthik K
KK
Shanmuganatham
Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Jeremy C
JC
Jones
Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Bindumadhav M
BM
Marathe
Department of Zoology, Jahangirnagar University, Dhaka 1342, Bangladesh.
Mohammed M
MM
Feeroz
National Primate Research Center University of Washington, Seattle, WA 98195-5502, USA.
Lisa
http://orcid.org/0000-0001-6912-494X
L
Jones-Engel
Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
David
D
Walker
Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Jasmine
J
Turner
Department of Zoology, Jahangirnagar University, Dhaka 1342, Bangladesh.
S M
SM
Rabiul Alam
Department of Zoology, Jahangirnagar University, Dhaka 1342, Bangladesh.
M
M
Kamrul Hasan
Department of Zoology, Jahangirnagar University, Dhaka 1342, Bangladesh.
Sharmin
S
Akhtar
Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Patrick
P
Seiler
Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Pamela
P
McKenzie
Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Scott
S
Krauss
Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Richard J
RJ
Webby
Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Robert G
RG
Webster
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D001459:Bangladesh / Q000453:epidemiology; D002460:Cell Line; D002645:Chickens / Q000821:virology; D005289:Ferrets / Q000821:virology; D005814:Genes, Viral; D006801:Humans; D066298:In Vitro Techniques; D057920:Influenza A Virus, H7N3 Subtype / Q000235:genetics* / Q000502:physiology; D053127:Influenza A Virus, H9N2 Subtype / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D005585:Influenza in Birds / Q000453:epidemiology / Q000821:virology; D007251:Influenza, Human / Q000453:epidemiology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D011201:Poultry Diseases / Q000821:virology; D011784:Quail / Q000821:virology; D016865:Reassortant Viruses / Q000235:genetics / Q000502:physiology*; D018570:Risk Assessment; D013552:Swine / Q000821:virology; D014779:Virus Replication
D000998:Antiviral Agents