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.[1] HHV-6 has an affinity for leukocytes and nervous tissue, especially the olfactory bulb tissues[2], 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 cells more susceptible to HHV-6 infection.[3]

In human disease[edit | edit source]

HHV-6 has been implicated as a possible contributing factor to a number of neurological diseases including multiple sclerosis[4], febrile seizures,[5] Alzheimer's disease[5], chronic fatigue syndrome[6], epilepsy including mesial temporal lope epilepsy (MTLE),[5] as well as fibromyalgia and AIDS.

HHV6a and HHV6b can infect multiple organs including the brain and central nervous system, salivary glands, tonsils, liver, kidneys, lymph nodes, endothelial cells, multiple types of white blood cells, plus several types of cell lines.[5]

Encephalitis[edit | edit source]

HHV-6B can cause encephalitis, particularly in people who are immunocompromised, especially after a hematopoietic cell transplantation.[5]

Multiple sclerosis[edit | edit source]

HHV-6 has been found in the oligodendrocytes of plaques in MS patients but not in healthy tissue.[7]

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.[8]. Valacyclovir reduced new lesions in patients with high disease activity.[9]

Cancer[edit | edit source]

Like Epstein-Barr virus, HHV-6 is associated with lymphomas and carcinomas.[3]

Chronic fatigue syndrome[edit | edit source]

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.[10] Several studies have found that active infection is more common in CFS patients than healthy controls.[6]

Possible treatments[edit | edit source]

Antivirals[edit | edit source]

There is no drug approved for treating HHV-6.[11] Those used clinically are the drugs used for human cytomegalovirus: ganciclovir (Cytovene IV), cidofovir (Vistide IV), and foscarnet (Foscavir IV).[11][12]

Notable studies[edit | edit source]

opinion article
  • 2020, Human Herpesvirus-6 Reactivation, Mitochondrial Fragmentation, and the Coordination of Antiviral and Metabolic Phenotypes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome[15] (Full text)
  • 2020, Cytomegalovirus, Epstein-Barr Virus, and Human herpesvirus-6 Infections in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome[16] - (Abstract)
  • 2020, Human Herpesviruses 6A and 6B in Brain Diseases: Association versus Causation[5] (Full text)

Learn more[edit | edit source]

See also[edit | edit source]

References[edit | edit source]

  1. ↑ Braun, D.K.; Dominguez, G.; Pellett, P.E. (July 1997). "Human herpesvirus 6". Clinical Microbiology Reviews. 10 (3): 521–567. ISSN 0893-8512. PMID 9227865.
  2. ↑ Harberts, Erin; Yao, Karen; Wohler, Jillian E.; Maric, Dragan; Ohayon, Joan; Henkin, Robert; Jacobson, Steven (August 16, 2011). "Human herpesvirus-6 entry into the central nervous system through the olfactory pathway". Proceedings of the National Academy of Sciences of the United States of America. 108 (33): 13734–13739. doi:10.1073/pnas.1105143108. ISSN 1091-6490. PMC 3158203. PMID 21825120.
  3. ↑ 3.0 3.1 De Bolle, Leen; Naesens, Lieve; De Clercq, Erik (January 2005). "Update on Human Herpesvirus 6 Biology, Clinical Features, and Therapy". Clinical Microbiology Reviews. 18 (1): 217–245. doi:10.1128/CMR.18.1.217-245.2005. ISSN 0893-8512. PMID 15653828.
  4. ↑ Pietiläinen-Nicklén, Jenna; Virtanen, Jussi O.; Uotila, Lasse; Salonen, Oili; Färkkilä, Markus; Koskiniemi, Marjaleena (October 2014). "HHV-6-positivity in diseases with demyelination". Journal of Clinical Virology. 61 (2): 216–219. doi:10.1016/j.jcv.2014.07.006. ISSN 1873-5967. PMID 25088617.
  5. ↑ 5.0 5.1 5.2 5.3 5.4 5.5 Komaroff, Anthony L.; Pellett, Philip E.; Jacobson, Steven (2020). "Human Herpesviruses 6A and 6B in Brain Diseases: Association versus Causation". Clinical Microbiology Reviews. 34 (1): e00143-20. doi:10.1128/cmr.00143-20. PMC 7667666. PMID 33177186.
  6. ↑ 6.0 6.1 Komaroff, Anthony L. (December 2006). "Is human herpesvirus-6 a trigger for chronic fatigue syndrome?". Journal of Clinical Virology: The Official Publication of the Pan American Society for Clinical Virology. 37 (Supp 1): S39–46. doi:10.1016/S1386-6532(06)70010-5. ISSN 1386-6532. PMID 17276367.
  7. ↑ Challoner, P.B.; Smith, K.T.; Parker, J.D.; MacLeod, D.L.; Coulter, S.N.; Rose, T.M.; Schultz, E.R.; Bennett, J.L.; Garber, R.L. (August 1, 1995). "Plaque-associated expression of human herpesvirus 6 in multiple sclerosis". Proceedings of the National Academy of Sciences of the United States of America. 92 (16): 7440–7444. doi:10.1073/pnas.92.16.7440. ISSN 0027-8424. PMID 7638210.
  8. ↑ Lycke, J.; Svennerholm, B.; Hjelmquist, E.; Frisén, L.; Badr, G.; Andersson, M.; Vahlne, A.; Andersen, O. (March 1996). "Acyclovir treatment of relapsing-remitting multiple sclerosis. A randomized, placebo-controlled, double-blind study". Journal of Neurology. 243 (3): 214–224. doi:10.1007/bf00868517. ISSN 0340-5354. PMID 8936350.
  9. ↑ Bech, E.; Lycke, J.; Gadeberg, P.; Hansen, H.J.; Malmeström, C.; Andersen, O.; Christensen, T.; Ekholm, S.; Haahr, S. (January 8, 2002). "A randomized, double-blind, placebo-controlled MRI study of anti-herpes virus therapy in MS". Neurology. 58 (1): 31–36. doi:10.1212/wnl.58.1.31. ISSN 0028-3878. PMID 11781402.
  10. ↑ Cuende, J.I.; Civeira, P.; Diez, N.; Prieto, J. (September 1997). "High prevalence without reactivation of herpes virus 6 in subjects with chronic fatigue syndrome". Anales De Medicina Interna. 14 (9): 441–444. ISSN 0212-7199. PMID 9453750.
  11. ↑ 11.0 11.1 "HHV-6 Treatment". HHV-6 Foundation. Retrieved March 1, 2020.
  12. ↑ Prichard, Mark N.; Whitley, Richard J. (December 2014). "The Development of New Therapies for Human Herpesvirus 6". Current opinion in virology. 0: 148–153. doi:10.1016/j.coviro.2014.09.019. ISSN 1879-6257. PMC 4267975. PMID 25462447.
  13. ↑ Aoki, R; Kobayashi, N; Suzuki, G; Kuratsune, H; Shimada, K; Oka, N; Takahashi, M; Yamadera, W; Iwashita, M; Tokuno, S; Nibuya, M; Tanichi, M; Mukai, Y; Mitani, K; Kondo, K; Ito, H; Nakayama, K (2016). "Human herpesvirus 6 and 7 are biomarkers for fatigue, which distinguish between physiological fatigue and pathological fatigue". Biochemical and Biophysical Research Communications. 478 (1): 424-30. doi:10.1016/j.bbrc.2016.07.010. PMID 27396623.
  14. ↑ Stoeger, Tobias; Adler, Heiko (2019). ""Novel" Triggers of Herpesvirus Reactivation and Their Potential Health Relevance". Frontiers in Microbiology. 9. doi:10.3389/fmicb.2018.03207. ISSN 1664-302X. PMC 6330347. PMID 30666238.
  15. ↑ Schreiner, Philipp; Harrer, Thomas; Scheibenbogen, Carmen; Lamer, Stephanie; Schlosser, Andreas; Naviaux, Robert K.; Prusty, Bhupesh K. (April 1, 2020). "Human Herpesvirus-6 Reactivation, Mitochondrial Fragmentation, and the Coordination of Antiviral and Metabolic Phenotypes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome". ImmunoHorizons. 4 (4): 201–215. doi:10.4049/immunohorizons.2000006. ISSN 2573-7732. PMID 32327453.
  16. ↑ Shikova, Evelina; Reshkova, Valentina; Kumanova, Аntoniya; Raleva, Sevdalina; Alexandrova, Dora; Capo, Natasa; Murovska, Modra (2020). "Cytomegalovirus, Epstein-Barr virus, and human herpesvirus-6 infections in patients with myalgic еncephalomyelitis/chronic fatigue syndrome". Journal of Medical Virology. doi:10.1002/jmv.25744. ISSN 1096-9071.

double blinded trial A clinical trial is double blinded if neither the participants nor the researchers know which treatment group they are allocated to until after the results are interpreted. This reduces bias. (Learn more: www.nottingham.ac.uk)

mitochondria Important parts of the biological cell, with each mitochondrion encased within a mitochondrial membrane. Mitochondria are best known for their role in energy production, earning them the nickname "the powerhouse of the cell". Mitochondria also participate in the detection of threats and the response to these threats. One of the responses to threats orchestrated by mitochondria is apoptosis, a cell suicide program used by cells when the threat can not be eliminated.

myalgic encephalomyelitis (M.E.) - A disease often marked by neurological symptoms, but fatigue is sometimes a symptom as well. Some diagnostic criteria distinguish it from chronic fatigue syndrome, while other diagnostic criteria consider it to be a synonym for chronic fatigue syndrome. A defining characteristic of ME is post-exertional malaise (PEM), or post-exertional neuroimmune exhaustion (PENE), which is a notable exacerbation of symptoms brought on by small exertions. PEM can last for days or weeks. Symptoms can include cognitive impairments, muscle pain (myalgia), trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, among others. An estimated 25% of those suffering from ME are housebound or bedbound. The World Health Organization (WHO) classifies ME as a neurological disease.

cytomegalovirus (CMV) - A common herpesvirus found in humans. Like other herpesviruses, it is a life-long infection that remains in a latent state inside the human body, until it is 'reactivated' by appropriate conditions. CMV infects between 60% to 70% of adults in industrialized countries and close to 100% in emerging countries. Much is unknown about this virus, although it has been found in salivary glands and myeloid blood cells such as monocytes. It has also been linked to the development of certain cancers. Congenital CMV is a leading infectious cause of deafness, learning disabilities, and intellectual disability. A common treatment for CMV is valganciclovir, commonly known as Valcyte.

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