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Non-cytolytic enterovirus
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== A brief history of non-cytolytic enterovirus == In the lifecycle of an acute lytic enterovirus infection, this virus will enter a host cell, replicate into thousands of new virions, destroying the cell by lysis in the process. However enterovirus, like most RNA viruses, is not capable of assuming a latent state within cells, and enterovirus infections are generally considered to be acute and rapidly cleared by the host immune response.<ref name="Kim2005-6">{{Cite journal | last = Kim | first = K.-S. | last2 = Tracy | first2 = S. | last3 = Tapprich | first3 = W. | last4 = Bailey | first4 = J. | last5 = Lee | first5 = C.-K. | last6 = Kim | first6 = K. | last7 = Barry | first7 = W.H. | last8 = Chapman | first8 = N.M. | date = Jun 2005 | title = 5'-Terminal deletions occur in coxsackievirus B3 during replication in murine hearts and cardiac myocyte cultures and correlate with encapsidation of negative-strand viral RNA|url=https://www.ncbi.nlm.nih.gov/pubmed/15890942/|journal=Journal of Virology|volume=79|issue=11 | pages = 7024β7041|doi=10.1128/JVI.79.11.7024-7041.2005|issn=0022-538X|pmc=1112132|pmid=15890942|quote=Picornavirus infections are generally considered to be acute and cleared rapidly by the host adaptive immune response.|via=}}</ref><ref name="Flynn2017" /> Indeed, John Chia points out that even today, most physicians are taught that enterovirus does not form chronic infections.<ref>{{Cite web|url=https://www.youtube.com/watch?v=IWxqftHYvqU&t=3m10s | title = Enteroviruses and Myalgic Encephalomyelitis / Chronic Fatigue Syndrome: An Update on Pathogenesis. Presentation at the Invest in ME International ME Conference, London 2015 (available on DVD). Timecode: 3:10. | last=Chia | first = John | date = 2015 | website = YouTube | archive-url=|archive-date=|url-status=|access-date= | authorlink = }}</ref> Thus it was puzzling why coxsackievirus B appeared capable of forming persistent infections in the heart muscle tissues in chronic CVB myocarditis and dilated cardiomyopathy, and in the skeletal muscle tissues in ME/CFS. Enteroviral RNA would be detected in these tissues, indicating an ongoing enterovirus infection, but infectious lytic virus can almost never be isolated from the adult heart in chronic myocarditis,<ref>{{Cite web|url=https://www.youtube.com/watch?v=3Ro7UlhSD-w&t=3m27s | title = How Does a Lytic Enterovirus Persist and Cause Chronic Disease? Enterovirus Session, International Symposium on Viruses in CFS & Post-viral Fatigue, Maryland, US, June 2008. Timecode: 3:27. | last=Chapman | first = Nora | date = 2008 | website = YouTube | archive-url=|archive-date=|url-status=|access-date=}}</ref> nor from the skeletal muscles in ME/CFS.Β (Lytic virus is detected by its cytopathic effect: when infected tissue samples are added to a cell culture in vitro, if lytic enterovirus is present it will lyse the cells in culture and this cytopathic effect can be observed; but a cytopathic effect is very rarely seen with chronic myocarditis, dilated cardiomyopathy and ME/CFS tissue samples). This was the conundrum for decades: how can enteroviral RNA be persistently present in these tissues, but without any lytic virus present? This paradox was eventually resolved by the discovery and understanding of the non-cytolytic form of enterovirus, which can create chronic intracellular infections of self-replicating enteroviral RNA, but with very little lytic virus generated.
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