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| __NOTOC__
| | #REDIRECT [[Chikungunya virus]] |
| {{Chikungunya}}
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| {{CMG}}; {{AE}} {{AL}}
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| ==Overview==
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| Chikungunya [[virus]] is an [[alphavirus]] with a positive sense single-stranded [[RNA]] genome of approximately 11.6kb. It is a member of the [[Semliki Forest Virus]] complex and is closely related to Ross River Virus, O’Nyong Nyong virus and [[Semliki Forest Virus]].<ref>{{cite journal|last=Powers|first=AM|coauthors=Brault, AC; Shirako, Y; Strauss, EG; Kang, W; Strauss, JH; Weaver, SC|title=Evolutionary relationships and systematics of the alphaviruses.|journal=Journal of Virology|date=Nov 2001|volume=75|issue=21|pages=10118–31|pmid=11581380|doi=10.1128/JVI.75.21.10118-10131.2001|pmc=114586}}</ref> In the United States it is classified as a Category C priority pathogen<ref>{{cite web|title=NIAID Category A, B, and C Priority Pathogens|url=http://www.niaid.nih.gov/topics/biodefenserelated/biodefense/pages/cata.aspx|accessdate=1 January 2014}}</ref> and work requires Biosafety Level 3 precautions.<ref>{{cite web|title=Biosafety in Microbiological and Biomedical Laboratories (BMBL) 5th Edition|url=http://www.cdc.gov/biosafety/publications/bmbl5/BMBL5_sect_VIII_f.pdf|accessdate=1 January 2014}}</ref>
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| Human [[epithelial]], [[endothelial]], primary [[fibroblasts]] and monocyte-derived [[macrophages]] are permissive for chikungunya [[virus]] ''[[in vitro]]'' and [[viral replication]] is highly cytopathic but susceptible to type I and II [[interferon]].<ref>{{cite journal|last=Sourisseau|first=M|coauthors=Schilte, C; Casartelli, N; Trouillet, C; Guivel-Benhassine, F; Rudnicka, D; Sol-Foulon, N; Le Roux, K; Prevost, MC; Fsihi, H; Frenkiel, MP; Blanchet, F; Afonso, PV; Ceccaldi, PE; Ozden, S; Gessain, A; Schuffenecker, I; Verhasselt, B; Zamborlini, A; Saïb, A; Rey, FA; Arenzana-Seisdedos, F; Desprès, P; Michault, A; Albert, ML; Schwartz, O|title=Characterization of reemerging chikungunya virus.|journal=PLoS Pathogens|date=Jun 2007|volume=3|issue=6|pages=e89|pmid=17604450|doi=10.1371/journal.ppat.0030089|pmc=1904475}}</ref> ''In vivo'', chikungunya [[virus]] appears to replicate in [[fibroblasts]], [[skeletal muscle]] progenitor cells and [[myofibers]].<ref name="Ozden e527">{{cite journal|last=Schilte|first=C|coauthors=Couderc, T; Chretien, F; Sourisseau, M; Gangneux, N; Guivel-Benhassine, F; Kraxner, A; Tschopp, J; Higgs, S; Michault, A; Arenzana-Seisdedos, F; Colonna, M; Peduto, L; Schwartz, O; Lecuit, M; Albert, ML|title=Type I IFN controls chikungunya virus via its action on nonhematopoietic cells.|journal=The Journal of experimental medicine|date=Feb 15, 2010|volume=207|issue=2|pages=429–42|pmid=20123960|doi=10.1084/jem.20090851|pmc=2822618}}</ref><ref>{{cite journal|last=Rohatgi|first=A|coauthors=Corbo, JC; Monte, K; Higgs, S; Vanlandingham, DL; Kardon, G; Lenschow, DJ|title=Infection of myofibers contributes to the increased pathogenicity during infection with an epidemic strain of Chikungunya Virus.|journal=Journal of Virology|date=Dec 11, 2013|pmid=24335291|doi=10.1128/JVI.02716-13|volume=88|issue=5|pages=2414–25}}</ref>
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| ==Virology==
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| {{Taxobox
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| | color=violet
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| | name = ''Chikungunya virus''
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| | virus_group = iv
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| | image = Emd-5577.jpg
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| | image_caption = [[Cryoelectron microscopy]] reconstruction of chikungunya virus.
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| | ordo = ''Unassigned''
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| | familia = ''[[Togaviridae]]''
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| | genus = ''[[Alphavirus]]''
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| | species = '''''Chikungunya virus'''''
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| }}
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| Chikungunya virus is an [[alphavirus]] with a positive sense single-stranded RNA genome of approximately 11.6kb. It is a member of the Semliki Forest Virus complex and is closely related to Ross River Virus, O’Nyong Nyong virus and [[Semliki Forest Virus]].<ref>{{cite journal|last=Powers|first=AM|coauthors=Brault, AC; Shirako, Y; Strauss, EG; Kang, W; Strauss, JH; Weaver, SC|title=Evolutionary relationships and systematics of the alphaviruses.|journal=Journal of Virology|date=Nov 2001|volume=75|issue=21|pages=10118–31|pmid=11581380|doi=10.1128/JVI.75.21.10118-10131.2001|pmc=114586}}</ref> In the United States it is classified as a Category C priority pathogen<ref>{{cite web|title=NIAID Category A, B, and C Priority Pathogens|url=http://www.niaid.nih.gov/topics/biodefenserelated/biodefense/pages/cata.aspx|accessdate=1 January 2014}}</ref> and work requires [[Biosafety level|Biosafety Level 3]] precautions.<ref>{{cite web|title=Biosafety in Microbiological and Biomedical Laboratories (BMBL) 5th Edition|url=http://www.cdc.gov/biosafety/publications/bmbl5/BMBL5_sect_VIII_f.pdf|accessdate=1 January 2014}}</ref> | |
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| Human epithelial, endothelial, primary fibroblasts and monocyte-derived macrophages are permissive for chikungunya virus ''in vitro'' and viral replication is highly cytopathic but susceptible to type I and II interferon.<ref>{{cite journal|last=Sourisseau|first=M|coauthors=Schilte, C; Casartelli, N; Trouillet, C; Guivel-Benhassine, F; Rudnicka, D; Sol-Foulon, N; Le Roux, K; Prevost, MC; Fsihi, H; Frenkiel, MP; Blanchet, F; Afonso, PV; Ceccaldi, PE; Ozden, S; Gessain, A; Schuffenecker, I; Verhasselt, B; Zamborlini, A; Saïb, A; Rey, FA; Arenzana-Seisdedos, F; Desprès, P; Michault, A; Albert, ML; Schwartz, O|title=Characterization of reemerging chikungunya virus.|journal=PLoS Pathogens|date=Jun 2007|volume=3|issue=6|pages=e89|pmid=17604450|doi=10.1371/journal.ppat.0030089|pmc=1904475}}</ref> ''In vivo'', chikungunya virus appears to replicate in fibroblasts, skeletal muscle progenitor cells and myofibers.<ref name="Ozden e527"/><ref>{{cite journal|last=Schilte|first=C|coauthors=Couderc, T; Chretien, F; Sourisseau, M; Gangneux, N; Guivel-Benhassine, F; Kraxner, A; Tschopp, J; Higgs, S; Michault, A; Arenzana-Seisdedos, F; Colonna, M; Peduto, L; Schwartz, O; Lecuit, M; Albert, ML|title=Type I IFN controls chikungunya virus via its action on nonhematopoietic cells.|journal=The Journal of experimental medicine|date=Feb 15, 2010|volume=207|issue=2|pages=429–42|pmid=20123960|doi=10.1084/jem.20090851|pmc=2822618}}</ref><ref>{{cite journal|last=Rohatgi|first=A|coauthors=Corbo, JC; Monte, K; Higgs, S; Vanlandingham, DL; Kardon, G; Lenschow, DJ|title=Infection of myofibers contributes to the increased pathogenicity during infection with an epidemic strain of Chikungunya Virus.|journal=Journal of Virology|date=Dec 11, 2013|pmid=24335291|doi=10.1128/JVI.02716-13|volume=88|issue=5|pages=2414–25}}</ref>
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| ===Type 1 interferon===
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| Upon infection with chikungunya, the host's [[fibroblasts]] will produce type 1 (alpha and beta) [[interferon]].<ref name="renamed_from_56_on_20130505003212">{{cite journal|author=Schilte C, Couderc T, Chretien F, et al. |title=Type I IFN controls chikungunya virus via its action on nonhematopoietic cells |journal=J. Exp. Med.|volume=207 |issue=2 |pages=429–42 |date=February 2010 |pmid=20123960 |pmc=2822618|doi=10.1084/jem.20090851}}</ref> Mice that lack the [[interferon alpha]] receptor die in 2–3 days upon being exposed to 10<sup>2</sup> chikungunya PFU, while wild type mice survive even when exposed to as much as 10<sup>6</sup> PFU of the virus.<ref name="renamed_from_56_on_20130505003212"/>
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| At the same time, mice that are partially type 1 deficient ([[IFN]] α/β +/−) are mildly affected and experience symptoms such as muscle weakness and lethargy.<ref>{{cite journal|author=Couderc T, Chrétien F, Schilte C, et al. |title=A mouse model for Chikungunya: young age and inefficient type-I interferon signaling are risk factors for severe disease|journal=PLoS Pathog. |volume=4 |issue=2 |pages=e29 |date=February 2008|pmid=18282093 |pmc=2242832 |doi=10.1371/journal.ppat.0040029}}</ref> Partidos et al. 2011 saw similar results with the live attenuated strain CHIKV181/25. However, rather than dying, the type 1 interferon deficient (IFN α/β −/−) mice were temporarily disabled and the partially [[type 1 interferon]] deficient mice did not have any problems.<ref>{{cite journal |author=Partidos CD, Weger J, Brewoo J, et al. |title=Probing the attenuation and protective efficacy of a candidate chikungunya virus vaccine in mice with compromised interferon (IFN) signaling |journal=Vaccine |volume=29 |issue=16|pages=3067–73 |date=April 2011 |pmid=21300099 |pmc=3081687|doi=10.1016/j.vaccine.2011.01.076}}</ref>
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| Several studies have attempted to find the upstream components of the [[type 1 interferon]] pathway involved in the host's response to chikungunya infection. So far, no one knows the chikungunya specific pathogen associated molecular pattern.<ref name=pmid209 >{{cite journal |author=White LK, Sali T, Alvarado D, et al. |title=Chikungunya virus induces IPS-1-dependent innate immune activation and protein kinase R-independent translational shutoff |journal=J. Virol. |volume=85 |issue=1 |pages=606–20 |date=January 2011|pmid=20962078 |pmc=3014158 |doi=10.1128/JVI.00767-10}}</ref> Nonetheless, IPS-1—also known as Cardif, MAVS, and VISA—has been found to be an important factor. In 2011, White et al. found that interfering with IPS-1 decreased the phosphorylation of interferon regulatory factor 3 ([[IRF3]]) and the production of IFN-β.<ref name=pmid209 /> Other studies have found that [[IRF3]] and [[IRF7]] are important in an age-dependent manner. Adult mice that lack both of these regulatory factors die upon infection with chikungunya.<ref>{{cite journal |author=Rudd PA, Wilson J, Gardner J, et al. |title=Interferon response factors 3 and 7 protect against Chikungunya virus hemorrhagic fever and shock|journal=J. Virol. |volume=86 |issue=18 |pages=9888–98 |date=September 2012|pmid=22761364 |pmc=3446587 |doi=10.1128/JVI.00956-12}}</ref> Neonates, on the other hand, succumb to the virus if they are deficient in one of these factors.<ref>{{cite journal|author=Schilte C, Buckwalter MR, Laird ME, Diamond MS, Schwartz O, Albert ML|title=Cutting edge: independent roles for IRF-3 and IRF-7 in hematopoietic and nonhematopoietic cells during host response to Chikungunya infection |journal=J. Immunol.|volume=188 |issue=7 |pages=2967–71 |date=April 2012 |pmid=22371392|doi=10.4049/jimmunol.1103185}}</ref>
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| Chikungunya counters the [[type I interferon]] response by producing NS2, a non-structural protein that degrades Rpb and turns off the host cell's ability to transcribe [[DNA]].<ref>{{cite journal |author=Akhrymuk I, Kulemzin SV, Frolova EI |title=Evasion of the innate immune response: the Old World alphavirus nsP2 protein induces rapid degradation of Rpb1, a catalytic subunit of RNA polymerase II |journal=J. Virol. |volume=86 |issue=13|pages=7180–91 |date=July 2012 |pmid=22514352 |pmc=3416352 |doi=10.1128/JVI.00541-12}}</ref> NS2 interferes with the [[JAK-STAT signaling pathway]] and prevents STAT from becoming phosphorylated.<ref>{{cite journal |author=Fros JJ, Liu WJ, Prow NA, et al.|title=Chikungunya virus nonstructural protein 2 inhibits type I/II interferon-stimulated JAK-STAT signaling |journal=J. Virol. |volume=84 |issue=20 |pages=10877–87 |date=October 2010 |pmid=20686047 |pmc=2950581 |doi=10.1128/JVI.00949-10}}</ref>
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| ==References==
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| {{reflist|2}}
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| [[Category:Disease]]
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| [[Category:Infectious disease]]
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| [[Category:Viral diseases]]
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| [[Category:Togaviruses]]
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| [[Category:Tropical disease]]
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