Chikungunya pathophysiology: Difference between revisions
Gerald Chi (talk | contribs) mNo edit summary |
m (Changes made per Mahshid's request) |
||
| (6 intermediate revisions by one other user not shown) | |||
| Line 2: | Line 2: | ||
{{Chikungunya}} | {{Chikungunya}} | ||
{{CMG}}; {{AE}} {{AL}} | {{CMG}}; {{AE}} {{AL}}, {{Alonso}}, {{VR}} | ||
==Overview== | ==Overview== | ||
[[CHIKV|Chikungunya virus (CHIKV)]] belongs to the [[alphavirus]] genus of the [[Togaviridae]] family and is transmitted by [[mosquito]] bites. Both [[innate immune response|innate]] and [[adaptive immune response|adaptive immunity]] are involved in the pathogenesis of CHIKV infection. | |||
==Pathophysiology== | |||
===Viral Transmission=== | |||
{| style="float: right;" | {| style="float: right;" | ||
| [[File:Ae aegypti ae albopictus.jpg|thumb|350px|Aedes mosquitoes transmit chikungunya virus to people.]] | | [[File:Ae aegypti ae albopictus.jpg|thumb|none|350px|Aedes mosquitoes transmit chikungunya virus to people.]] | ||
|- | |- | ||
| [[File:Chikungunya virus pathogenesis.png|thumb|350px|Chikungunya virus pathogenesis. <BR><SMALL>'' | | [[File:Chikungunya virus pathogenesis.png|thumb|none|350px|Chikungunya virus pathogenesis. <BR><SMALL>Adapted from ''Nat Rev Microbiol. 2010;8(7):491-500.<ref name="pmid20551973">{{cite journal| author=Schwartz O, Albert ML| title=Biology and pathogenesis of chikungunya virus. | journal=Nat Rev Microbiol | year= 2010 | volume= 8 | issue= 7 | pages= 491-500 | pmid=20551973 | doi=10.1038/nrmicro2368 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20551973 }} </ref>''</SMALL>]] | ||
|} | |} | ||
Chikungunya [[virus]] is primarily transmitted to humans through the bites of infected [[mosquitoes]], predominantly [[Aedes aegypti]] and [[Aedes albopictus]]. Humans are the primary host of | Chikungunya [[virus]] is primarily transmitted to humans through the bites of infected [[mosquitoes]], predominantly [[Aedes aegypti]] and [[Aedes albopictus]]. Humans are the primary host of Chikungunya [[virus]] during epidemic periods. Blood-borne transmission is possible; cases have been documented among laboratory personnel handling infected [[blood]] and a health care worker drawing blood from an infected patient. Rare ''[[in utero]]'' transmission has been documented mostly during the [[second trimester]]. Intrapartum transmission has also been documented when the mother was viremic around the time of delivery. Studies have not found Chikungunya [[virus]] in [[breast milk]]. The risk of a person transmitting the [[virus]] to a biting [[mosquito]] or through blood is highest when the patient is [[viremia|viremic]] during the first week of illness. | ||
===Cellular Tropism=== | |||
Following transmission through bites by infected mosquito (''[[Aedes aegypti]]'' or ''[[Aedes albopictus]]''), Chikungunya [[virus]] (CHIKV) replicates in the [[skin]] and [[fibroblasts]], enters the [[bloodstream]], and disseminates to the [[liver]], [[muscle]], [[joints]], [[lymphoid tissue]]s, and [[brain]]. After an incubation period of two to four days, affected individuals typically experience an abrupt onset of symptoms including high [[fever]], [[rigors]], [[headache]], [[photophobia]], incapacitating [[arthralgia]], and [[rash]] characterized by [[petechiae]] and/or [[maculopapular]] lesions. Unlike other members of arthritogenic [[alphavirus]], Chikungunya [[virus]] may also cause symptoms of [[meningoencephalitis]] and [[hemorrhage|hemorrhagic]] disease. Cellular tropism in infected humans correlates with the results from tissue culture experiments which showed replication of CHIKV in various cell lines including [[epithelial cell]]s, [[endothelial cell]]s, [[fibroblast]]s, muscle [[satellite cells]], and [[monocyte]]-derived [[macrophage]]s.<ref name="SourisseauSchilte2007">{{cite journal|last1=Sourisseau|first1=Marion|last2=Schilte|first2=Clémentine|last3=Casartelli|first3=Nicoletta|last4=Trouillet|first4=Céline|last5=Guivel-Benhassine|first5=Florence|last6=Rudnicka|first6=Dominika|last7=Sol-Foulon|first7=Nathalie|last8=Roux|first8=Karin Le|last9=Prevost|first9=Marie-Christine|last10=Fsihi|first10=Hafida|last11=Frenkiel|first11=Marie-Pascale|last12=Blanchet|first12=Fabien|last13=Afonso|first13=Philippe V.|last14=Ceccaldi|first14=Pierre-Emmanuel|last15=Ozden|first15=Simona|last16=Gessain|first16=Antoine|last17=Schuffenecker|first17=Isabelle|last18=Verhasselt|first18=Bruno|last19=Zamborlini|first19=Alessia|last20=Saïb|first20=Ali|last21=Rey|first21=Felix A.|last22=Arenzana-Seisdedos|first22=Fernando|last23=Desprès|first23=Philippe|last24=Michault|first24=Alain|last25=Albert|first25=Matthew L.|last26=Schwartz|first26=Olivier|title=Characterization of Reemerging Chikungunya Virus|journal=PLoS Pathogens|volume=3|issue=6|year=2007|pages=e89|issn=1553-7366|doi=10.1371/journal.ppat.0030089}}</ref><ref name="ZhangOzden2007">{{cite journal|last1=Zhang|first1=Linqi|last2=Ozden|first2=Simona|last3=Huerre|first3=Michel|last4=Riviere|first4=Jean-Pierre|last5=Coffey|first5=Lark L.|last6=Afonso|first6=Philippe V.|last7=Mouly|first7=Vincent|last8=de Monredon|first8=Jean|last9=Roger|first9=Jean-Christophe|last10=El Amrani|first10=Mohamed|last11=Yvin|first11=Jean-Luc|last12=Jaffar|first12=Marie-Christine|last13=Frenkiel|first13=Marie-Pascale|last14=Sourisseau|first14=Marion|last15=Schwartz|first15=Olivier|last16=Butler-Browne|first16=Gillian|last17=Desprès|first17=Philippe|last18=Gessain|first18=Antoine|last19=Ceccaldi|first19=Pierre-Emmanuel|title=Human Muscle Satellite Cells as Targets of Chikungunya Virus Infection|journal=PLoS ONE|volume=2|issue=6|year=2007|pages=e527|issn=1932-6203|doi=10.1371/journal.pone.0000527}}</ref> | |||
===Innate Immunity=== | |||
In parallel with the development of acute symptoms, the upsurge of [[viral load]] triggers the activation of the [[innate immune response]], hallmarked by the robust release of type I [[interferon]]s and other proinflammatory [[cytokines]] and [[chemokines]], which may be crucial to the control of CHIKV replication. Production of type I [[Interferon|interferons (IFNs)]] is initiated by the detection of [[PAMP|pathogen-associated molecular patterns]] such as surface [[glycoprotein]]s, single-stranded or double-stranded [[RNA]], and unmethylated [[CpG]]-containing [[DNA]]. [[TLR 3|Toll-like receptor 3 (TLR3)]], [[TLR 7|TLR7]], [[TLR 8|TLR8]], [[retinoic acid]]-inducible gene I-like receptors (RLRs), melanoma differentiation-associated protein 5 (MDA5), and other [[pattern recognition receptor|pattern recognition receptors (PRRs)]] have been suggested to engage the signalling cascade that leads to the activation of type I [[IFN]]s, which in turn triggers the [[transcription]] of [[interferon]]-stimulated genes that confer resistance to cells against CHIKV replication.<ref name="GillietCao2008">{{cite journal|last1=Gilliet|first1=Michel|last2=Cao|first2=Wei|last3=Liu|first3=Yong-Jun|title=Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases|journal=Nature Reviews Immunology|volume=8|issue=8|year=2008|pages=594–606|issn=1474-1733|doi=10.1038/nri2358}}</ref><ref name="SchwartzAlbert2010">{{cite journal|last1=Schwartz|first1=Olivier|last2=Albert|first2=Matthew L.|title=Biology and pathogenesis of chikungunya virus|journal=Nature Reviews Microbiology|volume=8|issue=7|year=2010|pages=491–500|issn=1740-1526|doi=10.1038/nrmicro2368}}</ref> Transient [[lymphopenia]] during acute infection may also be explained by the effects of type I [[interferon]]s rather than direct [[cytotoxicity]] of CHIKV, since [[B lymphocyte]]s and [[T lymphocyte]]s are not susceptible to CHIKV infection.<ref name="SolignatGay2009">{{cite journal|last1=Solignat|first1=Maxime|last2=Gay|first2=Bernard|last3=Higgs|first3=Stephen|last4=Briant|first4=Laurence|last5=Devaux|first5=Christian|title=Replication cycle of chikungunya: A re-emerging arbovirus|journal=Virology|volume=393|issue=2|year=2009|pages=183–197|issn=00426822|doi=10.1016/j.virol.2009.07.024}}</ref><ref name="KamphuisJunt2006">{{cite journal|last1=Kamphuis|first1=E.|last2=Junt|first2=T.|last3=Waibler|first3=Z.|last4=Forster|first4=R.|last5=Kalinke|first5=U.|title=Type I interferons directly regulate lymphocyte recirculation and cause transient blood lymphopenia|journal=Blood|volume=108|issue=10|year=2006|pages=3253–3261|issn=0006-4971|doi=10.1182/blood-2006-06-027599}}</ref> | |||
== | ===Adaptive Immunity=== | ||
In addition to the [[innate immune response|innate arm]] of the [[immune response]], [[T cells]] and [[antibody]]-mediated responses may also be involved in the rapid viral clearance that occurs approximately a week after infection. Relapsing [[rheumatic]] symptoms including [[polyarthritis]] and [[tenosynovitis]] have been reported in infected patients and may be related to the induction of [[autoimmunity]] caused by [[molecular mimicry]] between viral and host antigens. | |||
==References== | ==References== | ||
| Line 23: | Line 39: | ||
[[Category:Disease]] | [[Category:Disease]] | ||
[[Category:Viral diseases]] | [[Category:Viral diseases]] | ||
[[Category:Togaviruses]] | [[Category:Togaviruses]] | ||
[[Category:Tropical disease]] | [[Category:Tropical disease]] | ||
Latest revision as of 17:23, 18 September 2017
|
Chikungunya Microchapters |
|
Diagnosis |
|---|
|
Treatment |
|
Case Studies |
|
Chikungunya pathophysiology On the Web |
|
American Roentgen Ray Society Images of Chikungunya pathophysiology |
|
Risk calculators and risk factors for Chikungunya pathophysiology |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2], Alonso Alvarado, M.D. [3], Vendhan Ramanujam M.B.B.S [4]
Overview
Chikungunya virus (CHIKV) belongs to the alphavirus genus of the Togaviridae family and is transmitted by mosquito bites. Both innate and adaptive immunity are involved in the pathogenesis of CHIKV infection.
Pathophysiology
Viral Transmission
 |
 Adapted from Nat Rev Microbiol. 2010;8(7):491-500.[1] |
Chikungunya virus is primarily transmitted to humans through the bites of infected mosquitoes, predominantly Aedes aegypti and Aedes albopictus. Humans are the primary host of Chikungunya virus during epidemic periods. Blood-borne transmission is possible; cases have been documented among laboratory personnel handling infected blood and a health care worker drawing blood from an infected patient. Rare in utero transmission has been documented mostly during the second trimester. Intrapartum transmission has also been documented when the mother was viremic around the time of delivery. Studies have not found Chikungunya virus in breast milk. The risk of a person transmitting the virus to a biting mosquito or through blood is highest when the patient is viremic during the first week of illness.
Cellular Tropism
Following transmission through bites by infected mosquito (Aedes aegypti or Aedes albopictus), Chikungunya virus (CHIKV) replicates in the skin and fibroblasts, enters the bloodstream, and disseminates to the liver, muscle, joints, lymphoid tissues, and brain. After an incubation period of two to four days, affected individuals typically experience an abrupt onset of symptoms including high fever, rigors, headache, photophobia, incapacitating arthralgia, and rash characterized by petechiae and/or maculopapular lesions. Unlike other members of arthritogenic alphavirus, Chikungunya virus may also cause symptoms of meningoencephalitis and hemorrhagic disease. Cellular tropism in infected humans correlates with the results from tissue culture experiments which showed replication of CHIKV in various cell lines including epithelial cells, endothelial cells, fibroblasts, muscle satellite cells, and monocyte-derived macrophages.[2][3]
Innate Immunity
In parallel with the development of acute symptoms, the upsurge of viral load triggers the activation of the innate immune response, hallmarked by the robust release of type I interferons and other proinflammatory cytokines and chemokines, which may be crucial to the control of CHIKV replication. Production of type I interferons (IFNs) is initiated by the detection of pathogen-associated molecular patterns such as surface glycoproteins, single-stranded or double-stranded RNA, and unmethylated CpG-containing DNA. Toll-like receptor 3 (TLR3), TLR7, TLR8, retinoic acid-inducible gene I-like receptors (RLRs), melanoma differentiation-associated protein 5 (MDA5), and other pattern recognition receptors (PRRs) have been suggested to engage the signalling cascade that leads to the activation of type I IFNs, which in turn triggers the transcription of interferon-stimulated genes that confer resistance to cells against CHIKV replication.[4][5] Transient lymphopenia during acute infection may also be explained by the effects of type I interferons rather than direct cytotoxicity of CHIKV, since B lymphocytes and T lymphocytes are not susceptible to CHIKV infection.[6][7]
Adaptive Immunity
In addition to the innate arm of the immune response, T cells and antibody-mediated responses may also be involved in the rapid viral clearance that occurs approximately a week after infection. Relapsing rheumatic symptoms including polyarthritis and tenosynovitis have been reported in infected patients and may be related to the induction of autoimmunity caused by molecular mimicry between viral and host antigens.
References
- ↑ Schwartz O, Albert ML (2010). "Biology and pathogenesis of chikungunya virus". Nat Rev Microbiol. 8 (7): 491–500. doi:10.1038/nrmicro2368. PMID 20551973.
- ↑ Sourisseau, Marion; Schilte, Clémentine; Casartelli, Nicoletta; Trouillet, Céline; Guivel-Benhassine, Florence; Rudnicka, Dominika; Sol-Foulon, Nathalie; Roux, Karin Le; Prevost, Marie-Christine; Fsihi, Hafida; Frenkiel, Marie-Pascale; Blanchet, Fabien; Afonso, Philippe V.; Ceccaldi, Pierre-Emmanuel; Ozden, Simona; Gessain, Antoine; Schuffenecker, Isabelle; Verhasselt, Bruno; Zamborlini, Alessia; Saïb, Ali; Rey, Felix A.; Arenzana-Seisdedos, Fernando; Desprès, Philippe; Michault, Alain; Albert, Matthew L.; Schwartz, Olivier (2007). "Characterization of Reemerging Chikungunya Virus". PLoS Pathogens. 3 (6): e89. doi:10.1371/journal.ppat.0030089. ISSN 1553-7366.
- ↑ Zhang, Linqi; Ozden, Simona; Huerre, Michel; Riviere, Jean-Pierre; Coffey, Lark L.; Afonso, Philippe V.; Mouly, Vincent; de Monredon, Jean; Roger, Jean-Christophe; El Amrani, Mohamed; Yvin, Jean-Luc; Jaffar, Marie-Christine; Frenkiel, Marie-Pascale; Sourisseau, Marion; Schwartz, Olivier; Butler-Browne, Gillian; Desprès, Philippe; Gessain, Antoine; Ceccaldi, Pierre-Emmanuel (2007). "Human Muscle Satellite Cells as Targets of Chikungunya Virus Infection". PLoS ONE. 2 (6): e527. doi:10.1371/journal.pone.0000527. ISSN 1932-6203.
- ↑ Gilliet, Michel; Cao, Wei; Liu, Yong-Jun (2008). "Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases". Nature Reviews Immunology. 8 (8): 594–606. doi:10.1038/nri2358. ISSN 1474-1733.
- ↑ Schwartz, Olivier; Albert, Matthew L. (2010). "Biology and pathogenesis of chikungunya virus". Nature Reviews Microbiology. 8 (7): 491–500. doi:10.1038/nrmicro2368. ISSN 1740-1526.
- ↑ Solignat, Maxime; Gay, Bernard; Higgs, Stephen; Briant, Laurence; Devaux, Christian (2009). "Replication cycle of chikungunya: A re-emerging arbovirus". Virology. 393 (2): 183–197. doi:10.1016/j.virol.2009.07.024. ISSN 0042-6822.
- ↑ Kamphuis, E.; Junt, T.; Waibler, Z.; Forster, R.; Kalinke, U. (2006). "Type I interferons directly regulate lymphocyte recirculation and cause transient blood lymphopenia". Blood. 108 (10): 3253–3261. doi:10.1182/blood-2006-06-027599. ISSN 0006-4971.