title: Neuropathogenesis of Chikungunya infection: astrogliosis and innate immune activation.
abstract: Chikungunya, "that which bends up" in the Makonde dialect, is an emerging global health threat, with increasing incidence of neurological complications. Until 2013, Chikungunya infection had been largely restricted to East Africa and the Indian Ocean, with cases within the USA reported to be from foreign travel. However, in 2014, over 1 million suspected cases were reported in the Americas, and a recently infected human could serve as an unwitting reservoir for the virus resulting in an epidemic in the continental USA. Chikungunya infection is increasingly being associated with neurological sequelae. In this study, we sought to understand the role of astrocytes in the neuropathogenesis of Chikungunya infection. Even after virus has been cleared form the circulation, astrocytes were activated with regard to TLR2 expression. In addition, white matter astrocytes were hypertrophic, with increased arbor volume in gray matter astrocytes. Combined, these would alter the number and distribution of synapses that each astrocyte would be capable of forming. These results provide the first evidence that Chikungunya infection induces morphometric and innate immune activation of astrocytes in vivo. Perturbed glia-neuron signaling could be a major driving factor in the development of Chikungunya-associated neuropathology.
authors.affiliation: Tulane National Primate Research Center, Tulane Medical School, Covington, LA, 70433, USA.
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Inglis
authors.affiliation: Tulane National Primate Research Center, Tulane Medical School, Covington, LA, 70433, USA.
authors.forename: Kim M
authors.initials: KM
authors.lastname: Lee
authors.affiliation: Tulane National Primate Research Center, Tulane Medical School, Covington, LA, 70433, USA.
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Chiu
authors.affiliation: Tulane National Primate Research Center, Tulane Medical School, Covington, LA, 70433, USA.
authors.forename: Olivia M
authors.initials: OM
authors.lastname: Purcell
authors.affiliation: Tulane National Primate Research Center, Tulane Medical School, Covington, LA, 70433, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Didier
authors.affiliation: Tulane National Primate Research Center, Tulane Medical School, Covington, LA, 70433, USA.
authors.forename: Kasi
authors.initials: K
authors.lastname: Russell-Lodrigue
authors.affiliation: Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX, 77555-0610, USA.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Weaver
authors.affiliation: Tulane National Primate Research Center, Tulane Medical School, Covington, LA, 70433, USA.|Department of Microbiology & Immunology, Tulane Medical School, New Orleans, LA, 70112, USA.
authors.forename: Chad J
authors.initials: CJ
authors.lastname: Roy
authors.affiliation: Tulane National Primate Research Center, Tulane Medical School, Covington, LA, 70433, USA. amaclean@tulane.edu.|Department of Microbiology & Immunology, Tulane Medical School, New Orleans, LA, 70112, USA. amaclean@tulane.edu.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: MacLean
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000276:immunology / Q000473:pathology* / Q000821:virology; D065632:Chikungunya Fever / Q000235:genetics / Q000276:immunology / Q000473:pathology* / Q000821:virology; D002646:Chikungunya virus / Q000276:immunology / Q000472:pathogenicity; D004195:Disease Models, Animal; D015870:Gene Expression; D005911:Gliosis / Q000235:genetics / Q000276:immunology / Q000473:pathology* / Q000821:virology; D066128:Gray Matter / Q000276:immunology / Q000473:pathology / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D008252:Macaca fascicularis; D009474:Neurons / Q000276:immunology / Q000473:pathology* / Q000821:virology; D015398:Signal Transduction; D013686:Telemetry; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology; D066127:White Matter / Q000276:immunology / Q000473:pathology / Q000821:virology
chemical_list: D051195:Toll-Like Receptor 2
keywords: Alphavirus; Chikungunya; Gliosis; Morphometry; Togavirus; Toll-like receptor