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| __NOTOC__
| | #REDIRECT [[Chikungunya virus]] |
| {{Chikungunya}}
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| {{About0|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> 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]] 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 after exposure 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 interferon]] 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 (IFN-β promoter stimulator 1)—also known as Cardiff, MAVS (mitochondrial antiviral signaling protein), and VISA (virus-induced signaling adapter)—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|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 1 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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| ==Gallery==
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| <gallery>
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| Image: Alphavirus01.jpeg| Transmission electron micrograph (TEM) depicts numerous Chikungunya virus particles. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
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| Image: Alphavirus02.jpeg| At a magnification of 1000X, twice that of PHIL 10557, this scanning electron micrograph (SEM) revealed some of the minute exoskeletal details found at the proboscis tip of an unidentified mosquito found deceased in the suburbs of Decatur, Georgia <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
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| Image: Alphavirus03.jpeg| At a magnification of 1000X, twice that of PHIL 10557, this scanning electron micrograph (SEM) revealed some of the minute exoskeletal details found at the proboscis tip of an unidentified mosquito found deceased in the suburbs of Decatur, Georgia. The proboscis is the organ used by this, as well as other like insects, to feed upon the blood of a warm-blooded host, including human beings. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
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| Image: Alphavirus04.jpeg| Magnified 1500X, this scanning electron micrograph (SEM) revealed some of the minute exoskeletal details found at the proboscis tip of an unidentified mosquito found deceased in the suburbs of Decatur, Georgia. The proboscis is the organ used by this, as well as other like insects, to feed upon the blood of a warm-blooded host, including human beings. <SMALL><SMALL>''[http://phil.cdc.gov/phil/home.asp From Public Health Image Library (PHIL).] ''<ref name=PHIL> {{Cite web | title = Public Health Image Library (PHIL) | url = http://phil.cdc.gov/phil/home.asp}}</ref></SMALL></SMALL>
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| </gallery>
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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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