title: Replication and transmission of H9N2 influenza viruses in ferrets: evaluation of pandemic potential.
abstract: H9N2 avian influenza A viruses are endemic in poultry of many Eurasian countries and have caused repeated human infections in Asia since 1998. To evaluate the potential threat of H9N2 viruses to humans, we investigated the replication and transmission efficiency of H9N2 viruses in the ferret model. Five wild-type (WT) H9N2 viruses, isolated from different avian species from 1988 through 2003, were tested in vivo and found to replicate in ferrets. However these viruses achieved mild peak viral titers in nasal washes when compared to those observed with a human H3N2 virus. Two of these H9N2 viruses transmitted to direct contact ferrets, however no aerosol transmission was detected in the virus displaying the most efficient direct contact transmission. A leucine (Leu) residue at amino acid position 226 in the hemagglutinin (HA) receptor-binding site (RBS), responsible for human virus-like receptor specificity, was found to be important for the transmission of the H9N2 viruses in ferrets. In addition, an H9N2 avian-human reassortant virus, which contains the surface glycoprotein genes from an H9N2 virus and the six internal genes of a human H3N2 virus, showed enhanced replication and efficient transmission to direct contacts. Although no aerosol transmission was observed, the virus replicated in multiple respiratory tissues and induced clinical signs similar to those observed with the parental human H3N2 virus. Our results suggest that the establishment and prevalence of H9N2 viruses in poultry pose a significant threat for humans.
authors.affiliation: Department of Veterinary Medicine, University of Maryland, College Park, Maryland, United States of America.
authors.forename: Hongquan
authors.initials: H
authors.lastname: Wan
authors.forename: Erin M
authors.initials: EM
authors.lastname: Sorrell
authors.forename: Haichen
authors.initials: H
authors.lastname: Song
authors.forename: Md Jaber
authors.initials: MJ
authors.lastname: Hossain
authors.forename: Gloria
authors.initials: G
authors.lastname: Ramirez-Nieto
authors.forename: Isabella
authors.initials: I
authors.lastname: Monne
authors.forename: James
authors.initials: J
authors.lastname: Stevens
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cattoli
authors.forename: Ilaria
authors.initials: I
authors.lastname: Capua
authors.forename: Li-Mei
authors.initials: LM
authors.lastname: Chen
authors.forename: Ruben O
authors.initials: RO
authors.lastname: Donis
authors.forename: Julia
authors.initials: J
authors.lastname: Busch
authors.forename: James C
authors.initials: JC
authors.lastname: Paulson
authors.forename: Christy
authors.initials: C
authors.lastname: Brockwell
authors.forename: Richard
authors.initials: R
authors.lastname: Webby
authors.forename: Jorge
authors.initials: J
authors.lastname: Blanco
authors.forename: Mohammad Q
authors.initials: MQ
authors.lastname: Al-Natour
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Perez
mesh_terms: D000818:Animals; D001717:Birds; D003937:Diagnosis, Differential; D004195:Disease Models, Animal; D004196:Disease Outbreaks; D005289:Ferrets / Q000821:virology*; D006801:Humans; D053127:Influenza A Virus, H9N2 Subtype / Q000302:isolation & purification / Q000502:physiology*; D005585:Influenza in Birds / Q000453:epidemiology; D007251:Influenza, Human / Q000175:diagnosis / Q000453:epidemiology*; D008954:Models, Biological; D014779:Virus Replication; D015431:Weight Loss