Herpes simplex virus

From MEpedia, a crowd-sourced encyclopedia of ME and CFS science and history

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.[1]

Overview[edit | edit source]

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.)[1] HSV-1 is a highly common virus, found in an estimated 67% of the worldwide population under the age of 50.[1] HSV-1 is most contagious while symptomatic, but can also be transmitted while asymptomatic.[1]

HSV-2 is sexually transmitted and causes most cases of genital herpes.[1] HSV-2 infection increases the risk of contracting and transmitting HIV.[1] In the age group of 15 to 49, an estimated 11% of the global population has HSV-2.[1]

Treatment[edit | edit source]

Standard treatment for herpes simplex virus include acyclovir, famciclovir, and valacyclovir.[1] These medications can reduce frequency and severity of symptoms (but do not cure the infection).[1]

Basic research[edit | edit source]

An in vitro study found HSV-1 (as well as the influenza virus) inhibited the 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%.[2]

Implication in other diseases[edit | edit source]

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,[3] comprised of famciclovir (Famvir) and the COX-2 inhibitor drug celecoxib.[4] A randomized, double-blinded, placebo-controlled study clinical trial of 143 fibromyalgia patients by Pridgen et al. (2017) found IMC-1 safe and effective[5][6] and the US Food & Drug Administration (FDA) granted it fast-track designation for development as a fibromyalgia treatment.[7] A newer IMC-1 trial known as FORTRESS began recruiting fibromyalgia patients in 2021.[8]

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, chlamydia pneumoniae and several types of spirochatete",[9] 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.[10]

Several herpesviruses including HSV-2 may cause false positives on Lyme disease tests.[11]

Hypothesized role in ME/CFS[edit | edit source]

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 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.[12] 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,[13] 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.[14] The ME/CFS patients were those that met the Canadian Consensus Criteria.[14]

In 2018, Hector Bonilla, MD and Clinical Assistant Professor of Medicine in Infectious Diseases at Stanford University, received a Ramsay Award Grant from the Solve ME/CFS Initiative for a "Cross-sectional study to assess the prevalence of APOE e4 alleles in patients with ME/CFS and the association with herpes virus infection".[15] 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.[15]

Pridgen suggests that an approach related to IMC-1 also merits investigation as an ME/CFS treatment.[3]

News, interviews and articles[edit | edit source]

Notable studies[edit | edit source]

  • 1993, A role for herpes simplex virus in the aetiology of chronic fatigue syndrome and related disorders.[12] (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?[16]
  • 1996, Viral serologies in patients with chronic fatigue and chronic fatigue syndrome.[17]
  • 2002, Markers of viral infection in monozygotic twins discordant for chronic fatigue syndrome.[18]
  • 2006, Human herpesvirus 1 protein US3 induces an inhibition of mitochondrial electron transport[2]
  • 2013, Susceptibility genes are enriched in those of the herpes simplex virus 1/host interactome in psychiatric and neurological disorders.[19]

See also[edit | edit source]

Learn more[edit | edit source]

References[edit | edit source]

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 "Herpes simplex virus". World Health Organization. Retrieved April 22, 2019.
  2. ↑ 2.0 2.1 Derakhshan, Mohammad; Willcocks, Margaret M.; Salako, Michael A.; Kass, George E.N.; Carter, Michael J. (2006). "Human herpesvirus 1 protein US3 induces an inhibition of mitochondrial electron transport". Journal of General Virology. 87 (8): 2155–2159. doi:10.1099/vir.0.81949-0.
  3. ↑ 3.0 3.1 "Pipeline". Innovative Med Concepts. Retrieved April 22, 2019.
  4. ↑ Pridgen, William L. "Patent: Antiviral compound and cox-2 inhibitor combination therapy for functional somatic syndromes, including combination of famciclovir and celecoxib". Google patents.
  5. ↑ Pridgen, William L; Duffy, Carol; Gendreau, Judy F; Gendreau, R Michael (February 22, 2017). "A famciclovir + celecoxib combination treatment is safe and efficacious in the treatment of fibromyalgia". Journal of Pain Research. 10: 451–460. doi:10.2147/JPR.S127288. ISSN 1178-7090. PMC 5328426. PMID 28260944.
  6. ↑ Pridgen, W.; Duffy, C.; Gendreau, J.F.; Gendreau, R.M. (June 1, 2021). "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". Annals of the Rheumatic Diseases. 80 (Suppl 1): 210–210. doi:10.1136/annrheumdis-2021-eular.1424. ISSN 0003-4967.
  7. ↑ "Virios Therapeutics Achieves Over 50% Enrollment Milestone in its Phase 2b Clinical Trial for Fibromyalgia". Virios Therapeutics, Inc. Retrieved August 4, 2022.
  8. ↑ Virios Therapeutics, Inc. (May 13, 2022). "A Double-Blinded, Randomized, Placebo-Controlled, Phase 2B Trial of IMC-1 for the Treatment of Fibromyalgia". ClinicalTrials.gov. Retrieved August 4, 2022.
  9. ↑ Itzhaki, Ruth F.; Lathe, Richard; Balin, Brian J.; Ball, Melvyn J.; Bearer, Elaine L.; Braak, Heiko; Bullido, Maria J.; Carter, Chris; Clerici, Mario; Cosby, S. Louise; Del Tredici, Kelly (January 1, 2016). "Microbes and Alzheimer's Disease". Journal of Alzheimer's Disease. 51 (4): 979–984. doi:10.3233/JAD-160152. ISSN 1387-2877. PMC 5457904. PMID 26967229.
  10. ↑ Breijyeh, Zeinab; Karaman, Rafik (January 2020). "Comprehensive Review on Alzheimer's Disease: Causes and Treatment". Molecules. 25 (24): 5789. doi:10.3390/molecules25245789. ISSN 1420-3049.
  11. ↑ Berardi, Victor P.; Seder, Richard H.; Romanzi, Lauri; Strasfeld, Lynne (December 15, 2005). "False-Positive Serological Test Results for Lyme Disease in a Patient with Acute Herpes Simplex Virus Type 2 Infection". Clinical Infectious Diseases. 41 (12): 1826–1827. doi:10.1086/498319. ISSN 1058-4838.
  12. ↑ 12.0 12.1 Bond, P.A. (May 1993). "A role for herpes simplex virus in the aetiology of chronic fatigue syndrome and related disorders". Medical Hypotheses. 40 (5): 301–308. ISSN 0306-9877. PMID 8394501.
  13. ↑ Bond, P.A.; Dinan, T. G. (January 1, 2006). "Antibodies to Herpes Simplex Types 1 and 2 in Chronic Fatigue Syndrome". Journal of Chronic Fatigue Syndrome. 13 (1): 35–40. doi:10.1300/J092v13n01_04. ISSN 1057-3321.
  14. ↑ 14.0 14.1 Blomberg, Jonas; Rizwan, Muhammad; Böhlin-Wiener, Agnes; Elfaitouri, Amal; Julin, Per; Zachrisson, Olof; Rosén, Anders; Gottfries, Carl-Gerhard (2019). "Antibodies to Human Herpesviruses in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients". Frontiers in Immunology. 10: 1946. doi:10.3389/fimmu.2019.01946. ISSN 1664-3224. PMC 6702656. PMID 31475007.
  15. ↑ 15.0 15.1 "Hector Bonilla". Solve ME/CFS Initiative. Retrieved March 29, 2019.
  16. ↑ Manian, F.A. (September 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?". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 19 (3): 448–453. ISSN 1058-4838. PMID 7811864.
  17. ↑ Buchwald, D.; Ashley, R.L.; Pearlman, T.; Kith, P.; Komaroff, A.L. (September 1996). "Viral serologies in patients with chronic fatigue and chronic fatigue syndrome". Journal of Medical Virology. 50 (1): 25–30. doi:10.1002/(SICI)1096-9071(199609)50:13.0.CO;2-V. ISSN 0146-6615. PMID 8890037.
  18. ↑ Koelle, David M.; Barcy, Serge; Huang, Meei-Li; Ashley, Rhoda L.; Corey, Lawrence; Zeh, Judy; Ashton, Suzanne; Buchwald, Dedra (September 1, 2002). "Markers of viral infection in monozygotic twins discordant for chronic fatigue syndrome". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 35 (5): 518–525. doi:10.1086/341774. ISSN 1537-6591. PMID 12173124.
  19. ↑ Carter, Chris J. (December 2013). "Susceptibility genes are enriched in those of the herpes simplex virus 1/host interactome in psychiatric and neurological disorders". Pathogens and Disease. 69 (3): 240–261. doi:10.1111/2049-632X.12077. ISSN 2049-632X. PMID 23913659.
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