title: Contact heterogeneity, rather than transmission efficiency, limits the emergence and spread of canine influenza virus.
abstract: Host-range shifts in influenza virus are a major risk factor for pandemics. A key question in the study of emerging zoonoses is how the evolution of transmission efficiency interacts with heterogeneity in contact patterns in the new host species, as this interplay influences disease dynamics and prospects for control. Here we use a synergistic mixture of models and data to tease apart the evolutionary and demographic processes controlling a host-range shift in equine H3N8-derived canine influenza virus (CIV). CIV has experienced 15 years of continuous transfer among dogs in the United States, but maintains a patchy distribution, characterized by sporadic short-lived outbreaks coupled with endemic hotspots in large animal shelters. We show that CIV has a high reproductive potential in these facilities (mean R(0) = 3.9) and that these hotspots act as refugia from the sparsely connected majority of the dog population. Intriguingly, CIV has evolved a transmission efficiency that closely matches the minimum required to persist in these refugia, leaving it poised on the extinction/invasion threshold of the host contact network. Corresponding phylogenetic analyses show strong geographic clustering in three US regions, and that the effective reproductive number of the virus (R(e)) in the general dog population is close to 1.0. Our results highlight the critical role of host contact structure in CIV dynamics, and show how host contact networks could shape the evolution of pathogen transmission efficiency. Importantly, efficient control measures could eradicate the virus, in turn minimizing the risk of future sustained transmission among companion dogs that could represent a potential new axis to the human-animal interface for influenza.
authors.affiliation: Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey, United States of America.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Dalziel
authors.affiliation: Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
authors.forename: Kai
authors.initials: K
authors.lastname: Huang
authors.affiliation: Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Biological Sciences and Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Jemma L
authors.initials: JL
authors.lastname: Geoghegan
authors.affiliation: Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey, United States of America; Department of Infectious Disease Epidemiology, School of Public Health, Imperial College London, South Kensington Campus, London, United Kingdom.
authors.forename: Nimalan
authors.initials: N
authors.lastname: Arinaminpathy
authors.affiliation: Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Dubovi
authors.affiliation: Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey, United States of America; Fogarty International Center, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Bryan T
authors.initials: BT
authors.lastname: Grenfell
authors.affiliation: Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey, United States of America.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Ellner
authors.affiliation: Marie Bashir Institute for Infectious Diseases and Biosecurity, Charles Perkins Centre, School of Biological Sciences and Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Edward C
authors.initials: EC
authors.lastname: Holmes
authors.affiliation: Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
authors.forename: Colin R
authors.initials: CR
authors.lastname: Parrish
mesh_terms: D000818:Animals; D005075:Biological Evolution; D004195:Disease Models, Animal; D004285:Dogs; D006736:Horses; D058507:Host Specificity / Q000235:genetics*; D006801:Humans; D053123:Influenza A Virus, H3N8 Subtype; D007251:Influenza, Human / Q000821:virology*; D008969:Molecular Sequence Data; D009976:Orthomyxoviridae Infections; D012307:Risk Factors