title: Pandemic Swine-Origin H1N1 Influenza Virus Replicates to Higher Levels and Induces More Fever and Acute Inflammatory Cytokines in Cynomolgus versus Rhesus Monkeys and Can Replicate in Common Marmosets.
abstract: The close immunological and physiological resemblance with humans makes non-human primates a valuable model for studying influenza virus pathogenesis and immunity and vaccine efficacy against infection. Although both cynomolgus and rhesus macaques are frequently used in influenza virus research, a direct comparison of susceptibility to infection and disease has not yet been performed. In the current study a head-to-head comparison was made between these species, by using a recently described swine-origin pandemic H1N1 strain, A/Mexico/InDRE4487/2009. In comparison to rhesus macaques, cynomolgus macaques developed significantly higher levels of virus replication in the upper airways and in the lungs, involving both peak level and duration of virus production, as well as higher increases in body temperature. In contrast, clinical symptoms, including respiratory distress, were more easily observed in rhesus macaques. Expression of sialyl-α-2,6-Gal saccharides, the main receptor for human influenza A viruses, was 50 to 73 times more abundant in trachea and bronchus of cynomolgus macaques relative to rhesus macaques. The study also shows that common marmosets, a New World non-human primate species, are susceptible to infection with pandemic H1N1. The study results favor the cynomolgus macaque as model for pandemic H1N1 influenza virus research because of the more uniform and high levels of virus replication, as well as temperature increases, which may be due to a more abundant expression of the main human influenza virus receptor in the trachea and bronchi.
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Petra
authors.initials: P
authors.lastname: Mooij
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Gerrit
authors.initials: G
authors.lastname: Koopman
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Daniëlla
authors.initials: D
authors.lastname: Mortier
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Melanie
authors.initials: M
authors.lastname: van Heteren
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Herman
authors.initials: H
authors.lastname: Oostermeijer
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Fagrouch
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Rudy
authors.initials: R
authors.lastname: de Laat
authors.affiliation: National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
authors.forename: Gary
authors.initials: G
authors.lastname: Kobinger
authors.affiliation: National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Parasitology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Edmond J
authors.initials: EJ
authors.lastname: Remarque
authors.affiliation: Animal Science Department, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Ivanela
authors.initials: I
authors.lastname: Kondova
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Verschoor
authors.affiliation: Department of Virology, Biomedical Primate Research Centre, Rijswijk, The Netherlands.
authors.forename: Willy M J M
authors.initials: WM
authors.lastname: Bogers
mesh_terms: D000818:Animals; D002144:Callithrix / Q000821:virology*; D018925:Chemokines / Q000097:blood; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005334:Fever / Q000209:etiology; D058507:Host Specificity; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology*; D007251:Influenza, Human / Q000453:epidemiology / Q000276:immunology / Q000821:virology; D008168:Lung / Q000473:pathology; D008252:Macaca fascicularis / Q000276:immunology* / Q000821:virology*; D008253:Macaca mulatta / Q000276:immunology* / Q000821:virology*; D008297:Male; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000473:pathology / Q000821:virology; D058873:Pandemics; D011991:Receptors, Virus / Q000378:metabolism; D013552:Swine / Q000821:virology; D019562:Viral Load; D014774:Virulence / Q000276:immunology; D014779:Virus Replication
chemical_list: D018925:Chemokines; D016207:Cytokines; D018836:Inflammation Mediators; D011991:Receptors, Virus