Novel Highly Pathogenic Avian A(H5N2) and A(H5N8) Influenza Viruses of Clade 2.3.4.4 from North America Have Limited Capacity for Replication and Transmission in Mammals.
Highly pathogenic influenza A(H5N8) viruses from clade 2.3.4.4 were introduced to North America by migratory birds in the fall of 2014. Reassortment of A(H5N8) viruses with avian viruses of North American lineage resulted in the generation of novel A(H5N2) viruses with novel genotypes. Through sequencing of recent avian influenza viruses, we identified PB1 and NP gene segments very similar to those in the viruses isolated from North American waterfowl prior to the introduction of A(H5N8) to North America, highlighting these bird species in the origin of reassortant A(H5N2) viruses. While they were highly virulent and transmissible in poultry, we found A(H5N2) viruses to be low pathogenic in mice and ferrets, and replication was limited in both hosts compared with those of recent highly pathogenic avian influenza (HPAI) H5N1 viruses. Molecular characterization of the hemagglutinin protein from A(H5N2) viruses showed that the receptor binding preference, cleavage, and pH of activation were highly adapted for replication in avian species and similar to those of other 2.3.4.4 viruses. In addition, North American and Eurasian clade 2.3.4.4 H5NX viruses replicated to significantly lower titers in differentiated normal human bronchial epithelial cells than did seasonal human A(H1N1) and highly pathogenic A(H5N1) viruses isolated from a human case. Thus, despite their having a high impact on poultry, our findings suggest that the recently emerging North American A(H5N2) viruses are not expected to pose a substantial threat to humans and other mammals without further reassortment and/or adaptation and that reassortment with North American viruses has not had a major impact on viral phenotype. IMPORTANCE Highly pathogenic H5 influenza viruses have been introduced into North America from Asia, causing extensive morbidity and mortality in domestic poultry. The introduced viruses have reassorted with North American avian influenza viruses, generating viral genotypes not seen on other continents. The experiments and analyses presented here were designed to assess the impact of this genetic diversification on viral phenotypes, particularly as regards mammalian hosts, by comparing the North American viruses with their Eurasian precursor viruses.
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Bryan S
BS
Kaplan
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Marion
M
Russier
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Trushar
T
Jeevan
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Bindumadhav
B
Marathe
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Elena A
EA
Govorkova
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Charles J
CJ
Russell
National Veterinary Services Laboratories, Science, Technology and Analysis Services, Veterinary Services, Animal and Plant Health Inspection Service, U.S. Department of Agriculture, Ames, Iowa, USA.
Mia
M
Kim-Torchetti
College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, South Korea.
Young Ki
YK
Choi
Animal and Plant Health Agency, New Haw, Addlestone, Surrey, United Kingdom.
Ian
I
Brown
Influenza and Prion Disease Research Center, National Institute of Animal Health, National Agriculture and Food Research Organization, Tsukuba, Ibaraki, Japan.
Takehiko
T
Saito
Department of Population Health, College of Veterinary Medicine, The University of Georgia, Athens, Georgia, USA.
David E
DE
Stallknecht
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Scott
S
Krauss
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Richard J
RJ
Webby
H5N2; H5N8; avian influenza virus; mammals; viral replication