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Human herpesvirus 6
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'''Human herpesvirus 6''' (HHV-6) is a set of two closely related [[herpesviruses]], HHV6-A and HHV6-B. Infection is extremely common and usually occurs at an early age. 64-83% of infants are infected by age 13 months.<ref>{{Cite journal | last = Braun | first =D.K. | authorlink = | last2 = Dominguez | first2 = G. | authorlink2 = | last3 = Pellett | first3 = P.E. | authorlink3 = | date = Jul 1997 | title = Human herpesvirus 6 | url = https://www.ncbi.nlm.nih.gov/pubmed/9227865|journal=Clinical Microbiology Reviews|volume=10|issue=3 | pages = 521–567|doi=|issn=0893-8512|pmc=|pmid=9227865|access-date=|quote=|via=}}</ref> HHV-6 has an affinity for [[leukocyte]]s and nervous tissue, especially the [[olfactory bulb]] tissues<ref>{{Cite journal | last = Harberts | first = Erin | authorlink = | last2 = Yao | first2 = Karen | authorlink2 = | last3 = Wohler | first3 = Jillian E. | authorlink3 = | last4 = Maric | first4 = Dragan | authorlink4 = | last5 = Ohayon | first5 = Joan | authorlink5 = | last6 = Henkin | first6 = Robert | authorlink6 = | last7 = Jacobson | first7 = Steven | authorlink7 = | date = 2011-08-16 | title = Human herpesvirus-6 entry into the central nervous system through the olfactory pathway | url = https://www.ncbi.nlm.nih.gov/pubmed/21825120|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=108|issue=33|pages=13734–13739|doi=10.1073/pnas.1105143108|issn=1091-6490|pmc=3158203|pmid=21825120|access-date=|quote=|via=}}</ref>, from which it is thought to disseminate to other parts of the [[brain]]. After infection the virus remains latent but can reactivate asymptomatically even in healthy individuals. HHV-6 has been found to activate [[Epstein-Barr virus]] from latency. Conversely, the presence of EBV renders [[B cell]]s more susceptible to HHV-6 infection.<ref name="DeBolle2005">{{Cite journal | last = De Bolle | first = Leen | authorlink = | last2 = Naesens | first2 = Lieve | authorlink2 = | last3 = De Clercq | first3 = Erik | authorlink3 = | date = Jan 2005 | title = Update on Human Herpesvirus 6 Biology, Clinical Features, and Therapy | url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC544175/|journal=Clinical Microbiology Reviews|volume=18|issue=1 | pages = 217–245|doi=10.1128/CMR.18.1.217-245.2005|issn=0893-8512|pmc=|pmid=15653828|access-date=|quote=|via=}}</ref> ==In human disease== HHV-6 has been implicated as a possible contributing factor to a number of neurological diseases including [[multiple sclerosis]]<ref name="Pietilainen2014">{{Cite journal | last = Pietiläinen-Nicklén | first = Jenna | authorlink = | last2 = Virtanen | first2 = Jussi O. | authorlink2 = | last3 = Uotila | first3 = Lasse | authorlink3 = | last4 = Salonen | first4 = Oili | authorlink4 = | last5 = Färkkilä | first5 = Markus | authorlink5 = | last6 = Koskiniemi | first6 = Marjaleena | authorlink6 = | date = Oct 2014 | title = HHV-6-positivity in diseases with demyelination | url =https://www.ncbi.nlm.nih.gov/pubmed/25088617|journal=Journal of Clinical Virology|volume=61|issue=2 | pages = 216–219|doi=10.1016/j.jcv.2014.07.006|issn=1873-5967|pmc=|pmid=25088617|access-date=|quote=|via=}}</ref>, febrile seizures,<ref name="Komaroff2020b"/> [[Alzheimer's disease]]<ref name="Komaroff2020b"/>, [[chronic fatigue syndrome]]<ref name="Komaroff2006">{{Cite journal | last = Komaroff | first = Anthony L. | authorlink = Anthony Komaroff | date = Dec 2006 | title = Is human herpesvirus-6 a trigger for chronic fatigue syndrome? | url = https://www.ncbi.nlm.nih.gov/pubmed/17276367|journal=Journal of Clinical Virology: The Official Publication of the Pan American Society for Clinical Virology|volume=37 |issue=Supp 1|pages=S39–46|doi=10.1016/S1386-6532(06)70010-5|issn=1386-6532|pmc=|pmid=17276367|access-date=|quote=|via=}}</ref>, [[epilepsy]] including mesial temporal lope epilepsy (MTLE),<ref name="Komaroff2020b"/> as well as [[fibromyalgia]] and [[AIDS]]. HHV6a and HHV6b can infect multiple organs including the [[brain]] and [[central nervous system]], salivary glands, tonsils, [[liver]], [[kidney]]s, lymph nodes, [[endothelial dysfunction|endothelial cells]], multiple types of [[leukocyte|white blood cells]], plus several types of cell lines.<ref name="Komaroff2020b"/> ===Encephalitis=== HHV-6B can cause [[encephalitis]], particularly in people who are immunocompromised, especially after a hematopoietic cell transplantation.<ref name="Komaroff2020b"/> ===Multiple sclerosis=== HHV-6 has been found in the [[oligodendrocyte]]s of plaques in MS patients but not in healthy tissue.<ref>{{Cite journal | last = Challoner | first = P.B. | last2 = Smith | first2 = K.T. | last3 = Parker | first3 = J.D. | last4 = MacLeod | first4 =D.L. | last5 = Coulter | first5 = S.N. | last6 = Rose | first6 = T.M. | last7 = Schultz | first7 = E.R. | last8 = Bennett | first8 = J.L. | last9 = Garber | first9 = R.L. | date = 1995-08-01 | title = Plaque-associated expression of human herpesvirus 6 in multiple sclerosis | url = https://www.ncbi.nlm.nih.gov/pubmed/7638210/|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=92|issue=16 | pages = 7440–7444|doi=10.1073/pnas.92.16.7440|issn=0027-8424|pmid=7638210}}</ref> Antivirals may have some therapeutic benefit. A randomized, placebo-controlled double-blind study found that [[acyclovir]] reduced the exacerbation rate in relapsing-remitting MS patients.<ref>{{Cite journal | last = Lycke | first = J. | authorlink = | last2 = Svennerholm | first2 = B. | authorlink2 = | last3 = Hjelmquist | first3 = E. | authorlink3 = | last4 = Frisén | first4 = L. | authorlink4 = | last5 = Badr | first5 = G. | authorlink5 = | last6 = Andersson | first6 = M. | authorlink6 = | last7 = Vahlne | first7 = A. | last8 = Andersen | first8 = O. | date = Mar 1996 | title = Acyclovir treatment of relapsing-remitting multiple sclerosis. A randomized, placebo-controlled, double-blind study | url = https://www.ncbi.nlm.nih.gov/pubmed/8936350|journal=Journal of Neurology|volume=243|issue=3 | pages = 214–224|doi=10.1007/bf00868517|issn=0340-5354|pmc=|pmid=8936350|access-date=|quote=|via=}}</ref>. [[Valacyclovir]] reduced new lesions in patients with high disease activity.<ref>{{Cite journal | last = Bech | first = E. | last2 = Lycke | first2 = J. | last3 = Gadeberg | first3 = P. | last4 = Hansen | first4 = H.J. | last5 = Malmeström | first5 = C. | last6 = Andersen | first6 = O. | last7 = Christensen | first7 = T. | last8 = Ekholm | first8 = S. | last9 = Haahr | first9 = S. | date = 2002-01-08 | title = A randomized, double-blind, placebo-controlled MRI study of anti-herpes virus therapy in MS | url = https://www.ncbi.nlm.nih.gov/pubmed/11781402/|journal=Neurology|volume=58|issue=1 | pages = 31–36|doi=10.1212/wnl.58.1.31|issn=0028-3878|pmid=11781402}}</ref> ===Cancer=== Like [[Epstein-Barr virus]], HHV-6 is associated with [[lymphoma]]s and [[cancer|carcinomas]].<ref name="DeBolle2005" /> ==Chronic fatigue syndrome== Cuende et al. (1997) found a higher prevalence of past HHV-6 infection in [[chronic fatigue syndrome]] patients but with a low viral load that did not suggest reactivation.<ref name="Cuende1997">{{Cite journal | last = Cuende | first = J.I. | authorlink = | last2 = Civeira | first2 = P. | authorlink2 = | last3 = Diez | first3 = N. | authorlink3 = | last4 = Prieto | first4 = J. | authorlink4 = | date = Sep 1997 | title = High prevalence without reactivation of herpes virus 6 in subjects with chronic fatigue syndrome | url = https://www.ncbi.nlm.nih.gov/pubmed/9453750|journal=Anales De Medicina Interna|volume=14|issue=9 | pages = 441–444|doi=|issn=0212-7199|pmc=|pmid=9453750|access-date=|quote=|via=}}</ref> Several studies have found that active infection is more common in CFS patients than healthy controls.<ref name="Komaroff2006" /> ==Possible treatments == ===Antivirals=== There is no drug approved for treating HHV-6.<ref name="HH6Found-Treat" /> Those used clinically are the drugs used for human [[cytomegalovirus]]: [[ganciclovir]] (Cytovene IV), [[cidofovir]] (Vistide IV), and [[foscarnet]] (Foscavir IV).<ref name="HH6Found-Treat">{{Cite web | url=https://hhv-6foundation.org/clinicians/hhv-6-treatment | title = HHV-6 Treatment | last = | first = | authorlink = | date = | website = HHV-6 Foundation|archive-url=|archive-date=|url-status=|access-date=2020-03-01}}</ref><ref>{{Cite journal | last = Prichard | first = Mark N. | authorlink = | last2 = Whitley | first2 = Richard J. | authorlink2 = | date = Dec 2014 | title = The Development of New Therapies for Human Herpesvirus 6 | url = https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4267975/|journal=Current opinion in virology|volume=0|issue=|pages=148–153|doi=10.1016/j.coviro.2014.09.019|issn=1879-6257|pmc=4267975|pmid=25462447|access-date=|quote=|via=}}</ref> ==Notable studies== *1994, [http://onlinelibrary.wiley.com/doi/10.1111/j.1348-0421.1994.tb01827.x/pdf Prevalence of Human Herpesvirus 6 Variants A and B in Patients with Chronic Fatigue Syndrome] *2016, [https://www.ncbi.nlm.nih.gov/pubmed/27396623 Human herpesvirus 6 and 7 are biomarkers for fatigue, which distinguish between physiological fatigue and pathological fatigue]<ref name="Aoki, 2016" /> * 2019, "Novel" Triggers of Herpesvirus Reactivation and Their Potential Health Relevance<ref name="Stoeger2019">{{Cite journal|title=“Novel” Triggers of Herpesvirus Reactivation and Their Potential Health Relevance|date=2019|url=https://www.frontiersin.org/articles/10.3389/fmicb.2018.03207|journal=Frontiers in Microbiology|volume=9|last=Stoeger|first=Tobias|last2=Adler|first2=Heiko|doi=10.3389/fmicb.2018.03207|pmc=PMC6330347|pmid=30666238|issn=1664-302X}}</ref> - [[pmc:6330347|(Full text)]] ::opinion article *2020, Human Herpesvirus-6 Reactivation, Mitochondrial Fragmentation, and the Coordination of Antiviral and Metabolic Phenotypes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome<ref name="Schreiner2020">{{Cite journal | last = Schreiner | first = Philipp | author-link = | last2 = Harrer | first2 = Thomas | authorlink2 = Thomas Harrer | last3 = Scheibenbogen | first3 = Carmen | authorlink3 = Carmen Scheibenbogen | last4 = Lamer | first4 = Stephanie | authorlink4 = | last5 = Schlosser | first5 = Andreas | authorlink5 = | last6 = Naviaux | first6 = Robert K. | authorlink6 = Robert Naviaux | last7 = Prusty | first7 = Bhupesh K. | authorlink7 = Bhupesh Prusty | date = 2020-04-01 | title = Human Herpesvirus-6 Reactivation, Mitochondrial Fragmentation, and the Coordination of Antiviral and Metabolic Phenotypes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome | url = https://www.immunohorizons.org/content/4/4/201|journal=ImmunoHorizons|language=en|volume=4|issue=4 | pages = 201–215|doi=10.4049/immunohorizons.2000006|issn=2573-7732|pmc=|pmid=32327453|access-date=|quote=|via=}}</ref> [https://www.immunohorizons.org/content/4/4/201 (Full text)] *2020, Cytomegalovirus, Epstein-Barr Virus, and Human herpesvirus-6 Infections in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome<ref name="Shikova2020">{{Cite journal | last = Shikova | first = Evelina | authorlink = | last2 = Reshkova | first2 = Valentina | authorlink2 = | last3 = Kumanova | first3 = Аntoniya | authorlink3 = | last4 = Raleva | first4 = Sevdalina | authorlink4 = | last5 = Alexandrova | first5 = Dora | authorlink5 = | last6 = Capo | first6 = Natasa | authorlink6 = | last7 = Murovska | first7 = Modra | date = 2020 | title=Cytomegalovirus, Epstein-Barr virus, and human herpesvirus-6 infections in patients with myalgic еncephalomyelitis/chronic fatigue syndrome | url = https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.25744|journal=Journal of Medical Virology|language=en|volume=|issue=|pages=|doi=10.1002/jmv.25744|issn=1096-9071|pmc=|pmid=|access-date=|quote=|via=}}</ref> - [https://doi.org/10.1002/jmv.25744 (Abstract)] *2020, Human Herpesviruses 6A and 6B in Brain Diseases: Association versus Causation<ref name="Komaroff2020b">{{Cite journal | url = https://journals.asm.org/doi/abs/10.1128/CMR.00143-20 | title = Human Herpesviruses 6A and 6B in Brain Diseases: Association versus Causation | last = Komaroff | first = Anthony L. | authorlink = Anthony Komaroff | last2 = Pellett | first2 = Philip E. | authorlink2 = | last3 = Jacobson | first3 = Steven | date = 2020 | journal=Clinical Microbiology Reviews|volume=34|issue=1| pages = e00143-20|doi=10.1128/cmr.00143-20|pmc=7667666|pmid=33177186}}</ref> [https://journals.asm.org/doi/abs/10.1128/CMR.00143-20 (Full text)] ==Learn more== *[http://hhv-6foundation.org/ HHV-6 Foundation] *2016, [https://solvecfs.org/hhv-6-mediated-mitochondrial-modulation-and-its-possible-association-to-mecfs/ HHV-6 Mediated Mitochondrial Modulation and Its Association to ME/CFS] - Project summary for Solve ME/CFS Initiative *2018, [https://www.nytimes.com/2018/06/21/health/alzheimers-virus-herpes.html A Common Virus May Play Role in Alzheimer’s Disease, Study Finds] by Pam Belluck via NY Times ==See also== *[[HHV-7]] *[[Dharam Ablashi]] *[[List of herpesvirus infection studies]] ==References== <references> <ref name="Aoki, 2016">{{Cite journal | last =Aoki | first1 = R | authorlink1 = | last2 = Kobayashi | first2 = N | authorlink2 = | last3 = Suzuki | first3 = G | authorlink3 = | last4 = Kuratsune | first4 = H | authorlink4 = | last5 =Shimada | first5 = K | authorlink5 = | last6 = Oka | first6 = N | authorlink6 = | last7 = Takahashi | first7 = M | authorlink7 = | last8 =Yamadera | first8 = W | authorlink8 = | last9 = Iwashita | first9 = M | author-link9 = | last10 = Tokuno | first10 = S | authorlink10 = | last11 = Nibuya | first11 = M | authorlink11 = | last12 = Tanichi | first12 = M | authorlink12 = | last13 = Mukai | first13 = Y | authorlink13 = | last14 = Mitani | first14 = K | authorlink14 = | last15 = Kondo | first15 = K | authorlink15 = | last16 = Ito | first16 = H | authorlink16 = | last17 = Nakayama | first17 = K | authorlink17 = | title = Human herpesvirus 6 and 7 are biomarkers for fatigue, which distinguish between physiological fatigue and pathological fatigue | journal = Biochemical and Biophysical Research Communications | volume = 478 | issue = 1 | page = 424-30 | date = 2016 | pmid = 27396623 | doi = 10.1016/j.bbrc.2016.07.010 | url = https://doi.org/10.1016/j.bbrc.2016.07.010 }}</ref> </references> [[Category:Infectious agents]] [[Category:Triggers and risk factors]] [[Category:Virology]] [[Category:Viruses]]
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