title: Infectious Chikungunya Virus in the Saliva of Mice, Monkeys and Humans.
abstract: Chikungunya virus (CHIKV) is a reemerging, ordinarily mosquito-transmitted, alphavirus that occasionally produces hemorrhagic manifestations, such as nose bleed and bleeding gums, in human patients. Interferon response factor 3 and 7 deficient (IRF3/7-/-) mice, which are deficient for interferon α/β responses, reliably develop hemorrhagic manifestations after CHIKV infection. Here we show that infectious virus was present in the oral cavity of CHIKV infected IRF3/7-/- mice, likely due to hemorrhagic lesions in the olfactory epithelium that allow egress of infected blood into the nasal, and subsequently, oral cavities. In addition, IRF3/7-/- mice were more susceptible to infection with CHIKV via intranasal and oral routes, with IRF3/7-/- mice also able to transmit virus mouse-to-mouse without an arthropod vector. Cynomolgus macaques often show bleeding gums after CHIKV infection, and analysis of saliva from several infected monkeys also revealed the presence of viral RNA and infectious virus. Furthermore, saliva samples collected from several acute CHIKV patients with hemorrhagic manifestations were found to contain viral RNA and infectious virus. Oral fluids can therefore be infectious during acute CHIKV infections, likely due to hemorrhagic manifestations in the oral/nasal cavities.
authors.affiliation: Inflammation Biology Laboratory, QIMR Berghofer Medical Research Institute, and the Australian Infectious Diseases Research Centre, Brisbane, Queensland, Australia.
authors.forename: Joy
authors.initials: J
authors.lastname: Gardner
authors.affiliation: School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Penny A
authors.initials: PA
authors.lastname: Rudd
authors.affiliation: Inflammation Biology Laboratory, QIMR Berghofer Medical Research Institute, and the Australian Infectious Diseases Research Centre, Brisbane, Queensland, Australia.
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Prow
authors.affiliation: CEA, iMETI, Division of Immuno-Virology, Université Paris Sud and Center for immunology of viral infections and autoimmune diseases Inserm, UMR 1184, Fontenay-aux-Roses, France.
authors.forename: Essia
authors.initials: E
authors.lastname: Belarbi
authors.affiliation: CEA, iMETI, Division of Immuno-Virology, Université Paris Sud and Center for immunology of viral infections and autoimmune diseases Inserm, UMR 1184, Fontenay-aux-Roses, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Roques
authors.affiliation: Institut National de Recherche Agronomique, Nantes, France.
authors.forename: Thibaut
authors.initials: T
authors.lastname: Larcher
authors.affiliation: Sustainable Sciences Institute, Managua, Nicaragua.
authors.forename: Lionel
authors.initials: L
authors.lastname: Gresh
authors.affiliation: Laboratorio Nacional de Virología, Centro Nacional de Diagnóstico y Referencia, Ministry of Health, Managua, Nicaragua.
authors.forename: Angel
authors.initials: A
authors.lastname: Balmaseda
authors.affiliation: Division of Infectious Diseases and Vaccinology, School of Public Health, University of California Berkeley, Berkeley, CA, United States of America.
authors.forename: Eva
authors.initials: E
authors.lastname: Harris
authors.affiliation: Inflammation Biology Laboratory, QIMR Berghofer Medical Research Institute, and the Australian Infectious Diseases Research Centre, Brisbane, Queensland, Australia.
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Schroder
authors.affiliation: Inflammation Biology Laboratory, QIMR Berghofer Medical Research Institute, and the Australian Infectious Diseases Research Centre, Brisbane, Queensland, Australia.
authors.forename: Andreas
authors.initials: A
authors.lastname: Suhrbier
mesh_terms: D000293:Adolescent; D000818:Animals; D065632:Chikungunya Fever / Q000473:pathology* / Q000635:transmission / Q000821:virology; D002646:Chikungunya virus / Q000235:genetics* / Q000302:isolation & purification; D002648:Child; D004195:Disease Models, Animal; D005260:Female; D000882:Haplorhini; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000172:deficiency / Q000235:genetics; D050839:Interferon Regulatory Factor-7 / Q000172:deficiency / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009831:Olfactory Mucosa / Q000473:pathology / Q000821:virology; D012367:RNA, Viral / Q000378:metabolism; D012463:Saliva / Q000821:virology*; D019562:Viral Load
chemical_list: D050838:Interferon Regulatory Factor-3; D050839:Interferon Regulatory Factor-7; C494233:Irf3 protein, mouse; C494235:Irf7 protein, mouse; D012367:RNA, Viral