title: Active infection of human blood monocytes by Chikungunya virus triggers an innate immune response.
abstract: Chikungunya virus (CHIKV) is an alphavirus that causes chronic and incapacitating arthralgia in humans. To date, interactions between the immune system and the different stages of the virus life cycle remain poorly defined. We demonstrated for the first time that CHIKV Ags could be detected in vivo in the monocytes of acutely infected patients. Using in vitro experimental systems, whole blood and purified monocytes, we confirmed that monocytes could be infected and virus growth could be sustained. CHIKV interactions with monocytes, and with other blood leukocytes, induced a robust and rapid innate immune response with the production of specific chemokines and cytokines. In particular, high levels of IFN-alpha were produced rapidly after CHIKV incubation with monocytes. The identification of monocytes during the early phase of CHIKV infection in vivo is significant as infected monocyte/macrophage cells have been detected in the synovial tissues of chronically CHIKV-infected patients, and these cells may behave as the vehicles for virus dissemination. This may explain the persistence of joint symptoms despite the short duration of viremia. Our results provide a better understanding on the basic mechanisms of infection and early antiviral immune responses and will help in the development of future effective control strategies.
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Biopolis, Singapore.
authors.forename: Zhisheng
authors.initials: Z
authors.lastname: Her
authors.forename: Benoit
authors.initials: B
authors.lastname: Malleret
authors.forename: Monica
authors.initials: M
authors.lastname: Chan
authors.forename: Edward K S
authors.initials: EK
authors.lastname: Ong
authors.forename: Siew-Cheng
authors.initials: SC
authors.lastname: Wong
authors.forename: Dyan J C
authors.initials: DJ
authors.lastname: Kwek
authors.forename: Hugues
authors.initials: H
authors.lastname: Tolou
authors.forename: Raymond T P
authors.initials: RT
authors.lastname: Lin
authors.forename: Paul Anantharajah
authors.initials: PA
authors.lastname: Tambyah
authors.forename: Laurent
authors.initials: L
authors.lastname: Rénia
authors.forename: Lisa F P
authors.initials: LF
authors.lastname: Ng
mesh_terms: D000208:Acute Disease; D018354:Alphavirus Infections / Q000097:blood / Q000276:immunology*; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000821:virology; D002478:Cells, Cultured; D002646:Chikungunya virus / Q000276:immunology*; D002522:Chlorocebus aethiops; D002908:Chronic Disease; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D004195:Disease Models, Animal; D006801:Humans; D007113:Immunity, Innate; D007303:Insect Vectors / Q000276:immunology / Q000821:virology; D008251:Macaca; D008264:Macrophages / Q000276:immunology / Q000821:virology; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D022423:Myeloid Cells / Q000276:immunology / Q000821:virology; D014709:Vero Cells; D014766:Viremia / Q000276:immunology