title: Chikungunya fever: CNS infection and pathologies of a re-emerging arbovirus.
abstract: Chikungunya virus (CHIKV) is transmitted by Aedes mosquitoes and causes an acute symptomatic illness with fever, skin rash, and incapacitating arthralgia, which can evolve into chronic rheumatoid arthritis in elderly patients. This is a tropical disease originally described in central/east Africa in the 1960s, but its 2004 re-emergence in Africa and rapid spread in lands in and around the Indian Ocean (Reunion island, India, Malaysia) as well as Europe (Italy) led to almost 6 million cases worldwide. The risk of importation and spreading diseases with long-term sequelae is even greater today given the global distribution of the vectors (including in the Americas), increased tourism and the apparent capacity of CHIKV to produce high levels of viremia (10(9)-10(12) virus/ml of blood) and new mutants. CHIKV-associated neuropathology was described early in the 1960s, but it is the unprecedented incidence rate in Indian Ocean areas with efficient clinical facilities that allowed a better description of cases with severe encephalitis, meningoencephalitis, peripheral neuropathies and deaths among newborns (mother-to-child infection), infants and elderly patients. Death rates following CHIKV infection were estimated at 1:1000 cases in la Reunion's outbreak. These clinical observations have been corroborated by experimental infection in several mouse models, leading to CNS pathologies. We further describe in this review the capacity of CHIKV to infect neurons and glial cells, delineate the fundamental innate (intrinsic) immune defence mechanisms to protect from infection and argue about the possible mechanisms involved in the encephalopathy.
authors.affiliation: Immunopathology Infection Research Grouping, University and CHR Gelix Guyon of La Reunion, Saint Denis, 97400, Reunion.
authors.forename: Trina
authors.initials: T
authors.lastname: Das
authors.forename: Marie Christine
authors.initials: MC
authors.lastname: Jaffar-Bandjee
authors.forename: Jean Jacques
authors.initials: JJ
authors.lastname: Hoarau
authors.forename: Pascale
authors.initials: P
authors.lastname: Krejbich Trotot
authors.forename: Melanie
authors.initials: M
authors.lastname: Denizot
authors.forename: Ghislaine
authors.initials: G
authors.lastname: Lee-Pat-Yuen
authors.forename: Renubala
authors.initials: R
authors.lastname: Sahoo
authors.forename: Pascale
authors.initials: P
authors.lastname: Guiraud
authors.forename: Duksha
authors.initials: D
authors.lastname: Ramful
authors.forename: Stephanie
authors.initials: S
authors.lastname: Robin
authors.forename: Jean Luc
authors.initials: JL
authors.lastname: Alessandri
authors.forename: Bernard Alex
authors.initials: BA
authors.lastname: Gauzere
authors.forename: Philippe
authors.initials: P
authors.lastname: Gasque
mesh_terms: D018354:Alphavirus Infections / Q000175:diagnosis / Q000503:physiopathology / Q000821:virology; D000818:Animals; D020805:Central Nervous System Viral Diseases / Q000175:diagnosis / Q000503:physiopathology / Q000821:virology; D002646:Chikungunya virus / Q000472:pathogenicity*; D021821:Communicable Diseases, Emerging / Q000175:diagnosis / Q000503:physiopathology / Q000821:virology; D006801:Humans