Editing Viral onset hypothesis

{{Cleanup | reason=citations needed (see discussion page)  | date = 2015}}
The '''Viral onset hypothesis''' is a prominent theory and more than half of [[Myalgic encephalomyelitis|Myalgic Encephalomyelitis]]/[[Chronic fatigue syndrome|Chronic Fatigue Syndrome]] ([[ME/CFS]]) patients report falling ill after an acute viral infection.<ref name="canadianconsensus">{{Citation | last1   = Carruthers | first1 = Bruce M.      | authorlink1 = Bruce Carruthers  | last2   = Jain | first2 = Anil Kumar    | authorlink2 = Anil Kumar Jain | last3   = De Meirleir | first3 = Kenny L.      | authorlink3 = Kenny De Meirleir | last4   = Peterson  | first4 = Daniel L.     | authorlink4 = Daniel Peterson | last5   = Klimas | first5 = Nancy G.      | authorlink5 = Nancy Klimas | last6 = Lerner | first6 = A. Martin   | authorlink6 = Martin Lerner | last7   = Bested | first7 = Alison C.   | authorlink7 = Alison Bested | last8 = Flor-Henry  | first8 = Pierre      | authorlink8 = Pierre Flor-Henry  | last9 = Joshi  | first9 = Pradip        | authorlink9 = Pradip Joshi | last10  = Powles | first10 = A C Peter    | authorlink10 = A C Peter Powles | last11  = Sherkey  | first11 = Jeffrey A.   | authorlink11 = Jeffrey Sherkey | last12  = van de Sande  | first12 = Marjorie I.  | authorlink12 = Marjorie van de Sande | title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Clinical Working Case Definition, Diagnostic and Treatment Protocols | journal = Journal of Chronic Fatigue Syndrome | volume = 11 | issue = 2 | page = 7-115 | date = 2003
| pmid    = 
 | doi = 10.1300/J092v11n01_02
| url = http://www.investinme.org/Documents/PDFdocuments/CanadianDefinitionME-CFS.pdf }}</ref> Many different [[Virus|viruses]] have been researched as possible etiological agents.<ref name="canadianconsensus" />

==Theory==

==Disease onset==
Some think there is a single, novel viral agent as yet undiscovered. 

Others think many different viruses can initiate and sustain the disease. Viruses linked to disease onset include [[herpesviruses]] such as [[Epstein-Barr virus]] or [[Human herpesvirus 6]], [[enteroviruses]] such as [[coxsackie]] or even [[influenza]] (the [[flu]]) or a [[flu-like illness]].<ref name="canadianconsensus" /> Many viruses and pathogens have been investigated, with findings being mixed and no particular [[Portal:pathogens|pathogen]] found.<ref name="canadianconsensus" />

There are several hypotheses for how the viral trigger initiates and perpetuates the disease.

== Evidence ==
[[File:MEViralOnsetHypothesis.png|alt=Viral Onset Hypothesis in ME. Viral involvement is supported by an infectious initiating trigger in at least half of the patients (21), and by confirmed findings of biochemical dysregulation of the 2-5A synthetase/ribonuclease L (RNase L) antiviral defense pathway in monocytes (22,23,24,25,26), a pathway which is activated in viral disorders (27). - Canadian Consensus Criteria|thumb|Some evidence has exists supporting the viral onset hypothesis, but no pathogen has been identified yet.]] 

{{Clear}}

===Chronic infection===
Some think that there may be a low grade, chronic infection whereby the initial virus continues to provoke an immune response, especially in key areas such as the [[gastrointestinal tract]], [[muscle]], and the [[brain]], [[brain stem]], and [[spinal cord]]; an example is [[enterovirus infection hypothesis|enterovirus infection]].{{citation needed|date=2022}}

===Autoimmune disease===
Some think that symptoms are caused by an [[inflammatory]] process that is triggered by an initial infection and continues even after the initial [[virus]] is no longer replicating. It is possible that [[ME/CFS]] is an [[autoimmune disease|autoimmune]] response that can be triggered by many different infections.{{citation needed|date=2022}}

===Viral reactivation===
Some people think that an immune deficiency allows otherwise common or benign viruses to reactive after lying dormant, for instance [[Human herpesvirus 6]] and other common herpesviruses have been investigated.{{citation needed|date=2022}}

===Dysbiosis===
[[Viral infection]] may trigger intestinal [[dysbiosis]] leading to alterations in the [[immune system]] and [[gut-brain axis]] and causing the symptoms of the disease.{{citation needed|date=2022}}

===Outbreaks===
{{main article|page_name=List of outbreaks}}

There have been dozens of reported clusters and [[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks|outbreaks]] of ME, which all suggest a role of either a communicable [[pathogen]] or in some cases, a toxic agent, however some of these have been non-viral infections e.g. bacterial.<ref name="ICC2011primer"/>

==Evidence against ==
===Bacterial and non-viral infections as causes ===
There are many reports of non-viral infections e.g. bacterial infections or parasites leading to ME/CFS. Some of these have led to reported clusters and [[List of myalgic encephalomyelitis and chronic fatigue syndrome outbreaks|outbreaks]] of ME, for example a water poisoning with the parasite [[Giardia|Giardia lamblia]] caused the [[2004 Bergen, Norway outbreak]] and clusters of [[Q fever]] infections.{{citation needed|date=2022}}

===Non-infectious causes ===
The seminal Dubbo township study in [[Australia]] and a number of other very large [[ME/CFS]] studies have reported significant numbers of cases that were preceded by non-infectious events, for example serious accidents or injuries, routine vaccinations, or ongoing stress.<ref name="ICC2011primer">{{citation | last1 = Carruthers | first1 = BM | authorlink1 = Bruce Carruthers | last2 = van de Sande | first2 = MI | authorlink2 = Marjorie van de Sande | last3 = De Meirleir | first3 = KL | authorlink3 = Kenny de Meirleir | last4 = Klimas | first4 = NG | authorlink4 = Nancy Klimas| last5 = Broderick | first5 = G | authorlink5 = Gordon Broderick| last6 = Mitchell | first6 = T | authorlink6 = Terry Mitchell| last7 = Staines | first7 = D | authorlink7 = Donald Staines| last8 = Powles | first8 = ACP | authorlink8 = A C Peter Powles | last9 = Speight | first9 = N | authorlink9 = Nigel Speight | last10 = Vallings | first10 = R | authorlink10= Rosamund Vallings | last11 = Bateman | first11 =  L | authorlink11 = Lucinda Bateman | last12 = Bell | first12 = DS | authorlink12 = David Bell | last13 = Carlo-Stella | first13 =  N | authorlink13= Nicoletta Carlo-Stella | last14 = Chia | first14 =  J | authorlink14= John Chia | last15 = Darragh | first15 =  A | authorlink15= Austin Darragh | last16 = Gerken | first16 =  A | authorlink16= Anne Gerken | last17 = Jo | first17 =  D | authorlink17= Daehyun Jo | last18 = Lewis | first18 =  DP | authorlink18= Donald Lewis | last19 = Light | first19 =  AR | authorlink19= Alan Light | last20 = Light | first20 =  KC | authorlink20= Kathleen Light | last21 = Marshall-Gradisnik  | first21 =  S | authorlink21= Sonya Marshall-Gradisnik | last22 = McLaren-Howard | first22 =  J | authorlink22= John McLaren-Howard | last23 = Mena | first23 =  I | authorlink23= Ismael Mena | last24 = Miwa  | first24 =  K | authorlink24= Kunihisa Miwa | last25 = Murovska | first25 =  M | authorlink25= Modra Murovska | last26 = Stevens  | first26 =  SR | authorlink26= Staci Stevens | title = Myalgic encephalomyelitis: Adult & Paediatric: International Consensus Primer for Medical Practitioners | date = 2012| isbn = 978-0-9739335-3-6 | url = http://www.investinme.org/Documents/Guidelines/Myalgic%20Encephalomyelitis%20International%20Consensus%20Primer%20-2012-11-26.pdf}}</ref>

==Treatment==
[[Antiviral]]s are suggested as a potential treatment, but is known not to be universally effective in ME/CFS.{{citation needed|date=2022}}

==See also==
*[[Bacterial disease onset]]
*[[Enterovirus]]
*[[Herpesvirus]]
*[[Vagus nerve infection hypothesis]]

==Learn more==

==References ==
{{Reflist}}

[[Category:Medical hypotheses]]
[[Category:Triggers and risk factors]]
[[Category:Virology]]