title: Lack of transmission of a human influenza virus with avian receptor specificity between ferrets is not due to decreased virus shedding but rather a lower infectivity in vivo.
abstract: Influenza virus attaches to host cells by sialic acid (SA). Human influenza viruses show preferential affinity for α2,6-linked SA, whereas avian influenza viruses bind α2,3-linked SA. In this study, mutation of the haemagglutinin receptor-binding site of a human H3N2 influenza A virus to switch binding to α2,3-linked SA did not eliminate infection of ferrets but prevented transmission, even in a co-housed model. The mutant virus was shed from the noses of ferrets directly inoculated with virus in the same amounts and for the same length of time as wild-type virus. Mutant virus infection was localized to the same anatomical regions of the upper respiratory tract of directly inoculated animals. Interestingly, wild-type virus was more readily neutralized than the mutant virus in vitro by ferret nasal washes containing mucus. Moreover after inoculation of equal doses, the mutant virus grew poorly in ex vivo ferret nasal turbinate tissue compared with wild-type virus. The dose of mutant virus required to establish infection in the directly inoculated ferrets was 40-fold higher than for wild-type virus. It was concluded that minimum infectious dose is a predictor of virus transmissibility and it is suggested that, as virus passes from one host to another through stringent environmental conditions, viruses with a preference for α2,3-linked SA are unlikely to inoculate a new mammalian host in sufficient quantities to initiate a productive infection.
authors.affiliation: Department of Virology, Division of Infectious Disease, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK.
authors.forename: Kim L
authors.initials: KL
authors.lastname: Roberts
authors.affiliation: Department of Virology, Division of Infectious Disease, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK.
authors.forename: Holly
authors.initials: H
authors.lastname: Shelton
authors.affiliation: Center for the Study of Hepatitis C, The Rockefeller Univertity, New York, NY 10065, USA.|Cystic Fibrosis Center, University of North Carolina at Chapel Hill, NC 27599, USA.|Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, NC 27599, USA.|Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Margaret
authors.initials: M
authors.lastname: Scull
authors.affiliation: Cystic Fibrosis Center, University of North Carolina at Chapel Hill, NC 27599, USA.|Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, NC 27599, USA.
authors.forename: Raymond
authors.initials: R
authors.lastname: Pickles
authors.affiliation: Department of Virology, Division of Infectious Disease, Imperial College London, St Mary's Campus, Norfolk Place, London W2 1PG, UK.
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Barclay
mesh_terms: D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D005260:Female; D005289:Ferrets / Q000821:virology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics / Q000502:physiology*; D007251:Influenza, Human / Q000378:metabolism / Q000635:transmission* / Q000821:virology*; D011485:Protein Binding; D011991:Receptors, Virus / Q000378:metabolism*; D012137:Respiratory System / Q000378:metabolism / Q000821:virology; D013045:Species Specificity; D014420:Turbinates / Q000378:metabolism / Q000821:virology; D014779:Virus Replication; D017201:Virus Shedding
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011991:Receptors, Virus; C109963:hemagglutinin, avian influenza A virus