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Herpes simplex virus
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'''Herpes simplex virus''' 1 and 2 ('''HSV-1''' and '''HSV-2'''), also known as human [[herpesvirus]] 1 and 2 (HHV-1 and HHV-2), are two members of the eight known members of the '''herpesviridae''' family. Both are lifelong infections and mostly asymptomatic.<ref name="WHO">{{Cite web | url=https://www.who.int/news-room/fact-sheets/detail/herpes-simplex-virus | title = Herpes simplex virus|website=[[World Health Organization]]|language=en|access-date=2019-04-22}}</ref> == Overview == HSV-1 is mainly transmitted by oral contact and causes cold sores, but can also cause genital herpes (persons with oral HSV-1 are unlikely to subsequently contract genital HSV-1.)<ref name="WHO" /> HSV-1 is a highly common virus, found in an estimated 67% of the worldwide population under the age of 50.<ref name="WHO" /> HSV-1 is most contagious while symptomatic, but can also be transmitted while asymptomatic.<ref name="WHO" /> HSV-2 is sexually transmitted and causes most cases of genital herpes.<ref name="WHO" /> HSV-2 infection increases the risk of contracting and transmitting [[HIV]].<ref name="WHO" /> In the age group of 15 to 49, an estimated 11% of the global population has HSV-2.<ref name="WHO" /> == Treatment == Standard treatment for herpes simplex virus include [[Aciclovir|acyclovir]], [[famciclovir]], and [[valacyclovir]].<ref name="WHO" /> These medications can reduce frequency and severity of symptoms (but do not cure the infection).<ref name="WHO" /> == Basic research == An [[In vitro studies|in vitro study]] found HSV-1 (as well as the [[Influenza|influenza virus]]) inhibited the [[mitochondrion|mitochondrial]] respiratory chain. In the case of HSV-1, it reduced [[cellular respiration]] by targeting a site between complexes II and III, mediated by protein US3, and reduced the [[oxygen]] consumption rate by 31%.<ref name="Derakhshan2006">{{Cite journal | last = Derakhshan | first = Mohammad | last2 = Willcocks | first2 = Margaret M. | last3 = Salako | first3 = Michael A. | last4 = Kass | first4 = George E.N. | last5 = Carter | first5 = Michael J. | date = 2006 | title=Human herpesvirus 1 protein US3 induces an inhibition of mitochondrial electron transport | url = https://jgv.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.81949-0|journal=Journal of General Virology|volume=87|issue=8 | pages = 2155–2159|doi=10.1099/vir.0.81949-0|quote=|via=}}</ref> == Implication in other diseases == Dr. [[William Pridgen]] hypothesizes that [[fibromyalgia]] may be caused by HSV-1 infection in the [[dorsal root ganglia]] of the spine (and/or in other nerve ganglia), and treats fibromyalgia with an antiviral combination drug, called [[IMC-1]],<ref name="IMC-2019">{{Cite web | url=http://innovativemedconcepts.com/pipeline.html | title = Pipeline|website=Innovative Med Concepts|access-date=2019-04-22}}</ref> comprised of [[famciclovir]] (Famvir) and the [[COX-2 inhibitors|COX-2 inhibitor]] drug [[celecoxib]].<ref>{{Cite web | url=https://patents.google.com/patent/US20130203710 | title = Patent: Antiviral compound and cox-2 inhibitor combination therapy for functional somatic syndromes, including combination of famciclovir and celecoxib | last = Pridgen | first = William L. | authorlink = | date = | website = Google patents|archive-url=|archive-date=|url-status=|access-date=}}</ref> A randomized, double-blinded, placebo-controlled study clinical trial of 143 fibromyalgia patients by Pridgen et al. (2017) found IMC-1 safe and effective<ref name="Pridgen2017a">{{Cite journal | last = Pridgen | first = William L | last2 = Duffy | first2 = Carol | last3 = Gendreau | first3 = Judy F | last4 = Gendreau | first4 = R Michael | date = 2017-02-22 | title = A famciclovir + celecoxib combination treatment is safe and efficacious in the treatment of fibromyalgia | url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5328426/|journal=Journal of Pain Research|volume=10 | pages = 451–460|doi=10.2147/JPR.S127288|issn=1178-7090|pmc=5328426|pmid=28260944|issue=|quote=|via=}}</ref><ref name="Pridgen2017b">{{Cite journal | title = Pos0017 Imc-1, a Fixed Dose Combination of Famciclovir and Celecoxib, Improves Common Symptoms Associated with Fibromyalgia in Addition to Pain: Post Hoc Analysis of a Phase 2a Trial | date = 2021-06-01 | url = https://ard.bmj.com/content/80/Suppl_1/210.1|journal=Annals of the Rheumatic Diseases|volume=80|issue=Suppl 1 | pages = 210–210 | last = Pridgen | first = W. | last2 = Duffy | first2 = C. | last3 = Gendreau | first3 = J.F. | last4 = Gendreau | first4 = R.M.|language=en|doi=10.1136/annrheumdis-2021-eular.1424|issn=0003-4967}}</ref> and the US Food & Drug Administration (FDA) granted it fast-track designation for development as a fibromyalgia treatment.<ref name="Press2021">{{Cite web | url=https://ir.virios.com/news/press-releases/detail/70/virios-therapeutics-achieves-over-50-enrollment-milestone | title = Virios Therapeutics Achieves Over 50% Enrollment Milestone in its Phase 2b Clinical Trial for Fibromyalgia|website=Virios Therapeutics, Inc.|language=en|access-date=2022-08-04}}</ref> A newer IMC-1 trial known as FORTRESS began recruiting fibromyalgia patients in 2021.<ref name="FORTRESS-trial">{{Cite web | title = A Double-Blinded, Randomized, Placebo-Controlled, Phase 2B Trial of IMC-1 for the Treatment of Fibromyalgia | date = 2022-05-13 | url = https://clinicaltrials.gov/ct2/show/NCT04748705|journal=ClinicalTrials.gov|volume=|issue=|pages = | last = Virios Therapeutics, Inc. | first = | authorlink = |access-date=Aug 4, 2022|quote=|via=}}</ref> Itzhaki et al. (2017) has hypothesized that [[Alzheimer's disease]] may be caused by viral or bacterial infection, noting "many studies, mainly on humans, implicating specific microbes in the elderly brain, notably herpes simplex virus type 1, [[Chlamydophila pneumoniae|chlamydia pneumoniae]] and several types of spirochatete",<ref name="Itzhaki 2017">{{Cite journal | title = Microbes and Alzheimer’s Disease | date = 2016-01-01 | url = https://content.iospress.com/articles/journal-of-alzheimers-disease/jad160152|journal=Journal of Alzheimer's Disease|volume=51|issue=4 | pages = 979–984 | last = Itzhaki | first = Ruth F. | last2 = Lathe | first2 = Richard | last3 = Balin | first3 = Brian J. | last4 = Ball | first4 = Melvyn J. | last5 = Bearer | first5 = Elaine L. | last6 = Braak | first6 = Heiko | last7 = Bullido | first7 = Maria J. | last8 = Carter | first8 = Chris | last9 = Clerici | first9 = Mario | last10 = Cosby | first10 = S. Louise | last11 = Del Tredici | first11 = Kelly|language=en|doi=10.3233/JAD-160152|pmc=PMC5457904|pmid=26967229|issn=1387-2877}}</ref> although there is clear evidence supporting this hypothesis, it is currently not one of the two top hypotheses about the cause of Alzheimer's disease.<ref name="Breijyeh2020">{{Cite journal | title = Comprehensive Review on Alzheimer’s Disease: Causes and Treatment | date = Jan 2020 | url = https://www.mdpi.com/1420-3049/25/24/5789 | journal = Molecules | volume = 25 | issue = 24 | page = 5789 | last = Breijyeh | first = Zeinab | authorlink = | last2 = Karaman | first2 = Rafik | authorlink2 = |language=en | doi = 10.3390/molecules25245789|pmc=|pmid=|access-date=|issn=1420-3049|quote=|via=}}</ref> Several herpesviruses including HSV-2 may cause false positives on [[Lyme disease]] tests.<ref name="Strasfeld2005">{{Cite journal | last = Berardi | first = Victor P. | last2 = Seder | first2 = Richard H. | last3 = Romanzi | first3 = Lauri | last4 = Strasfeld | first4 = Lynne | date = 2005-12-15 | title = False-Positive Serological Test Results for Lyme Disease in a Patient with Acute Herpes Simplex Virus Type 2 Infection | url =https://academic.oup.com/cid/article/41/12/1826/346681|journal=Clinical Infectious Diseases|language=en|volume=41|issue=12|pages=1826–1827|doi=10.1086/498319|issn=1058-4838|quote=|via=}}</ref> ==Hypothesized role in ME/CFS== In a 1993 paper in ''Medical Hypotheses (journal)'', P. A. Bond hypothesized that HSV-1 could cause the symptoms of [[chronic fatigue syndrome]] (CFS) in a two-stage process Bond analogized to the relationship of [[HIV/AIDS|HIV to AIDS]]: as (untreated) HIV weakens the immune system and makes the body vulnerable to opportunistic infections and cancers, which then are recognized as the symptoms of AIDS, Bond suggests a variety of conditions could produce immune dysfunction and consequent vulnerability to HSV-1 (either primary infection or reactivation), which in turn could be the cause of a range of CFS symptoms.<ref name="Bond1993">{{Cite journal | last = Bond | first = P.A. | authorlink = | date = May 1993 | title = A role for herpes simplex virus in the aetiology of chronic fatigue syndrome and related disorders | url = https://www.ncbi.nlm.nih.gov/pubmed/8394501|journal=Medical Hypotheses|volume=40|issue=5 | pages = 301–308|issn=0306-9877|pmid=8394501|quote=|via=}}</ref> In 2006, Bond did a study of 27 CFS patients meeting the [[Fukuda criteria]], and found that antibodies to both HSV-1 and HSV-2 were more common in CFS patients that controls,<ref name="Bond2006">{{Cite journal | title = Antibodies to Herpes Simplex Types 1 and 2 in Chronic Fatigue Syndrome | date = 2006-01-01 | url = https://doi.org/10.1300/J092v13n01_04|journal=Journal of Chronic Fatigue Syndrome|volume=13|issue=1 | pages = 35–40 | last = Bond | first = P.A. | last2 = Dinan | first2 = T. G. |doi=10.1300/J092v13n01_04|issn=1057-3321}}</ref> however a larger study by Blomberg et al. (2019) found levels of HSV-1 and HSV-2 in ME/CFS and fibromyalgia patients were similar to or slightly lower than those of healthy blood donors.<ref name="Blomgberg2019">{{Cite journal | title = Antibodies to Human Herpesviruses in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients | date = 2019 | url=https://www.frontiersin.org/articles/10.3389/fimmu.2019.01946|journal=Frontiers in Immunology|volume=10|issue=|pages=1946 | last = Blomberg | first = Jonas | authorlink = Jonas Blomberg | last2 = Rizwan | first2 = Muhammad | authorlink2 = Muhammad Rizwan | last3 = Böhlin-Wiener | first3 = Agnes | authorlink3 = | last4 = Elfaitouri | first4 = Amal | authorlink4 = | last5 = Julin | first5 = Per | authorlink5 = | last6 = Zachrisson | first6 = Olof | authorlink6 = Olof Zachrisson | last7 = Rosén | first7 = Anders | last8 = Gottfries | first8 = Carl-Gerhard | authorlink8 = Carl-Gerhard Gottfries|doi=10.3389/fimmu.2019.01946|pmc=PMC6702656|pmid=31475007|access-date=|issn=1664-3224|quote=|via= }}</ref> The ME/CFS patients were those that met the [[Canadian Consensus Criteria]].<ref name="Blomgberg2019" /> In 2018, [[Hector Bonilla]], MD and Clinical Assistant Professor of Medicine in Infectious Diseases at [[Stanford University]], received a [[Ramsay Award Program|Ramsay Award Grant]] from the [[Solve ME/CFS Initiative]] for a "Cross-sectional study to assess the prevalence of [[Apolipoprotein E|APOE]] e4 alleles in patients with ME/CFS and the association with herpes virus infection".<ref name="Solve2019">{{Cite web | url=https://solvecfs.org/hector-bonilla/ | title = Hector Bonilla|website=Solve ME/CFS Initiative|language=en-US|access-date=2019-03-29}}</ref> The project follows on preliminary findings that HSV-1 infection in the sera of individuals with ME/CFS is related to severity of the disease.<ref name="Solve2019" /> Pridgen suggests that an approach related to IMC-1 also merits investigation as an ME/CFS treatment.<ref name="IMC-2019" /> ==News, interviews and articles == *2016, [https://www.telegraph.co.uk/news/science/science-news/12188092/Alzheimers-disease-could-be-caused-by-herpes-virus-warn-experts.html Alzheimer's disease could be caused by herpes virus, warn experts] - The Telegraph ==Notable studies== * 1993, A role for herpes simplex virus in the aetiology of chronic fatigue syndrome and related disorders.<ref name="Bond1993" /> ([https://vdocuments.site/a-role-for-herpes-simplex-virus-in-the-aetiology-of-chronic-fatigue-syndrome.html Full text]) * 1994, Simultaneous measurement of antibodies to Epstein-Barr virus, human herpesvirus 6, herpes simplex virus types 1 and 2, and 14 enteroviruses in chronic fatigue syndrome: is there evidence of activation of a nonspecific polyclonal immune response?<ref name="Manian1994">{{Cite journal | last = Manian | first = F.A. | date = Sep 1994 | title = Simultaneous measurement of antibodies to Epstein-Barr virus, human herpesvirus 6, herpes simplex virus types 1 and 2, and 14 enteroviruses in chronic fatigue syndrome: is there evidence of activation of a nonspecific polyclonal immune response? | url = https://www.ncbi.nlm.nih.gov/pubmed/7811864|journal=Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America|volume=19|issue=3 | pages = 448–453|issn=1058-4838|pmid=7811864|quote=|via=}}</ref> * 1996, Viral serologies in patients with chronic fatigue and chronic fatigue syndrome.<ref name="Buchwald1996">{{Cite journal | last = Buchwald | first =D. | last2 = Ashley | first2 = R.L. | last3 = Pearlman | first3 = T. | last4 = Kith | first4 = P. | last5 = Komaroff | first5 = A.L. | date = Sep 1996 | title = Viral serologies in patients with chronic fatigue and chronic fatigue syndrome | url = https://www.ncbi.nlm.nih.gov/pubmed/8890037|journal=Journal of Medical Virology|volume=50|issue=1 | pages = 25–30|doi=10.1002/(SICI)1096-9071(199609)50:13.0.CO;2-V|issn=0146-6615|pmid=8890037|quote= | author-link = Dedra Buchwald | authorlink2 = | authorlink3 = | authorlink4 = | authorlink5 = Anthony Komaroff|via=}}</ref> * 2002, Markers of viral infection in monozygotic twins discordant for chronic fatigue syndrome.<ref name="Koelle2002">{{Cite journal | last = Koelle | first = David M. | last2 = Barcy | first2 = Serge | last3 = Huang | first3 = Meei-Li | last4 = Ashley | first4 = Rhoda L. | last5 = Corey | first5 = Lawrence | last6 = Zeh | first6 = Judy | last7 = Ashton | first7 = Suzanne | last8 = Buchwald | first8 = Dedra | date = 2002-09-01 | title = Markers of viral infection in monozygotic twins discordant for chronic fatigue syndrome | url = https://www.ncbi.nlm.nih.gov/pubmed/12173124|journal=Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America|volume=35|issue=5 | pages = 518–525|doi=10.1086/341774|issn=1537-6591|pmid=12173124|quote=|via= | authorlink6 = | last9 = | authorlink7 = | authorlink8 = Dedra Buchwald}}</ref> * 2006, Human herpesvirus 1 protein US3 induces an inhibition of mitochondrial electron transport<ref name="Derakhshan2006" /> * 2013, Susceptibility genes are enriched in those of the herpes simplex virus 1/host interactome in psychiatric and neurological disorders.<ref name="Carter2013">{{Cite journal | last = Carter | first = Chris J. | date = Dec 2013 | title = Susceptibility genes are enriched in those of the herpes simplex virus 1/host interactome in psychiatric and neurological disorders | url = https://www.ncbi.nlm.nih.gov/pubmed/23913659|journal=Pathogens and Disease|volume=69|issue=3 | pages = 240–261|doi=10.1111/2049-632X.12077|issn=2049-632X|pmid=23913659|quote=|via=}}</ref> ==See also== *[[Infection]] *[[:Category:Triggers and risk factors|Triggers and risk factors]] *[[:Category:Virology|Virology]] *[[Vagus nerve infection hypothesis]] *[[List of herpesvirus infection studies]] ==Learn more == ==References== {{Reflist}} [[Category:Viruses]] [[Category:Infectious agents]] [[Category:Triggers and risk factors]] [[Category:Virology]] [[Category:Herpesviruses]]
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