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List of herpesvirus infection studies
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Herpesvirus family viruses including [[Epstein-Barr virus]], [[human herpesvirus 6]] (HHV-6) and [[cytomegalovirus]] are associated with [[myalgic encephalomyelitis]]. This article lists herpesvirus studies examining the role and prevalence of herpesviruses in ME/CFS patients. Positive studies (finding herpesvirus more prevalent in ME/CFS patients than healthy controls) are indicated by a <big class="green">'''+'''</big> symbol, whereas negative studies (finding no significant difference in prevalence between patients and healthy controls) are indicated by the <big class="red">'''−'''</big> symbol. ==Epstein-Barr virus studies== Epstein-Barr virus (EBV) is found in 95% of the adult population (usually in a latent state),<ref name="CDC-about">{{Cite web|url=https://www.cdc.gov/epstein-barr/about-ebv.html | title = Epstein-barr {{!}} Mononucleosis {{!}} About Virus {{!}} Mono {{!}} CDC | date = 2019-01-28 | website = [[Centers for Disease Control and Prevention]]|language=en-us|access-date=2020-08-19}}</ref> and is the most common cause of [[mononucleosis]]. {| class="wikitable alternance" ! scope="col" style="width: 10px;" | ! scope="col" style="width: 270px;" | Study Title ! scope="col" style="width: 32px;" | Date ! scope="col" style="Xwidth: 200px;" | Details |- |'''<big class="green">+</big>''' |'''Chronic fatigue syndrome: clinical condition associated with immune activation''' A L Landay, C Jessop, E T Lennette, J A Levy<ref>{{Cite journal|last = Landay|first = A.L. | last2 = Jessop | first2 = C. | last3 = Lennette | first3 = E.T. | last4 = Levy | first4 = J.A. | date = 1991-09-21 | title = Chronic fatigue syndrome: clinical condition associated with immune activation | url =https://pubmed.ncbi.nlm.nih.gov/1679864/|journal=Lancet (London, England)|volume=338|issue=8769 | pages = 707–712|doi=10.1016/0140-6736(91)91440-6|issn=0140-6736|pmid=1679864}}</ref> |1991 |This study found CFS patients had a significantly higher prevalence of antibodies to EBV-EA (Early Antigen) than did controls; 32 of 63 (51%) patients compared to 6 of 40 (15%) controls. |- |'''<big class="green">+</big>''' |'''Persistent virus infection of muscle in postviral fatigue syndrome''' L Cunningham, N E Bowles, L C Archard<ref>{{Cite journal|last = Cunningham|first = L. | last2 = Bowles | first2 = N.E. | last3 = Archard | first3 = L.C. | date = Oct 1991 | title = Persistent virus infection of muscle in postviral fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/1665379/|journal=British Medical Bulletin|volume=47|issue=4 | pages = 852–871|doi=10.1093/oxfordjournals.bmb.a072516|issn=0007-1420|pmid=1665379}}</ref> |1991 |[[Postviral fatigue syndrome|Postviral Fatigue Syndrome]] (PVFS) patients suffering from chronic muscle fatiguability were studied to test their association with viral infection versus healthy controls. EBV DNA was found in muscle biopsies in 8 of 86 (9%) PVFS patients and in 0 of 36 (0%) controls. |- |'''<big class="green">+</big>''' |'''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?''' F A Manian<ref>{{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://pubmed.ncbi.nlm.nih.gov/7811864/|journal=Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America|volume=19|issue=3 | pages = 448–453|doi=10.1093/clinids/19.3.448|issn=1058-4838|pmid=7811864}}</ref> |1994 |20 patients with CFS and 20 age- and gender-matched controls were compared to test for potential differences in viral antibody titers. EBV viral capsid antigen (VCA) IgG was present at titers ≥ 1:320 in 11 of 20 (55%) CFS patients vs. 3 of 20 (15%) Controls. |- |'''<big class="red">−</big>''' |'''Viral serologies in patients with chronic fatigue and chronic fatigue syndrome''' [[Dedra Buchwald]], Rhoda L. Ashley, Tsilke Pearlman, Phalla Kith, and Anthony L. Komaroff<ref name="Buchwald1996b">{{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://pubmed.ncbi.nlm.nih.gov/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}}</ref> |1996 |Large study was performed on CFS patients and healthy control subjects to compare antibodies to various viruses. Epstein-Barr virus antibody results shown in table below. {| class="wikitable transparent" ! !VCA IgG >1:640 !VCA IgM Positive !Early Antigen (EA) Positive |- |CFS Patients |24 of 308 (8%) |2 of 310 (1%) |56 of 306 (18%) |- |Healthy Controls |1 of 30 (3%) |1 of 30 (3%) |7 of 30 (23%) |} |- |'''<big class="green">+</big>''' |'''Diagnostic evaluation of 2′, 5′-oligoadenylate synthetase activities and antibodies against Epstein–Barr virus and Coxiella burnetii in patients with chronic fatigue syndrome in Japan''' Kazufumi Ikuta, Takeshi Yamada, Tokio Shimomura, Hirohiko Kuratsune, Ryuzo Kawahara, Shiro Ikawa, Eiko Ohnishi, Yoshihiro Sokawa, Hideto Fukushi, Katsuya Hirai, Yasuyoshi Watanabe, Takeshi Kurata, Teruo Kitani, Takeshi Sairenji<ref>{{Cite journal|last = Ikuta | first = Kazufumi | last2 = Yamada | first2 = Takeshi | last3 = Shimomura | first3 = Tokio | last4 = Kuratsune | first4 = Hirohiko | last5 = Kawahara | first5 = Ryuzo | last6 = Ikawa | first6 = Shiro | last7 = Ohnishi | first7 = Eiko | last8 = Sokawa | first8 = Yoshihiro | last9 = Fukushi | first9 = Hideto | date = Oct 2003 | title = Diagnostic evaluation of 2′, 5′-oligoadenylate synthetase activities and antibodies against Epstein–Barr virus and Coxiella burnetii in patients with chronic fatigue syndrome in Japan | url =https://www.sciencedirect.com/science/article/abs/pii/S1286457903002193|journal=Microbes and Infection|language=en|volume=5|issue=12|pages=1096–1102|doi=10.1016/j.micinf.2003.07.002|issn=1286-4579}}</ref> |2003 |A total of 44 ME/CFS patients from two Japanese hospitals located in different areas of the country were tested for EBV Early Antigen (EA) antibodies, and were compared to healthy controls. EA IgG was found positive in 9 of 44 (20%) CFS patients and 0 of 9 (0%) controls. |- |'''<big class="green">+</big>''' |'''IgM serum antibodies to Epstein-Barr virus are uniquely present in a subset of patients with the chronic fatigue syndrome''' [[A Martin Lerner]], Safedin H Beqaj, Robert G Deeter, James T Fitzgerald<ref>{{Cite journal|last = Lerner | first = A. Martin | last2 = Beqaj | first2 = Safedin H. | last3 = Deeter | first3 = Robert G. | last4 = Fitzgerald | first4 = James T. | date = Mar 2004 | title = IgM serum antibodies to Epstein-Barr virus are uniquely present in a subset of patients with the chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/15113035/|journal=In Vivo (Athens, Greece)|volume=18|issue=2|pages=101–106|issn=0258-851X|pmid=15113035}}</ref> |2004 |58 ME/CFS patients and 68 non-CFS matched controls were studied for possible active EBV infection through serum antibodies. VCA IgM was positive in 33 of 58 (57%) CFS patients and 5 of 68 (7%) controls. Early Antigen (EA) IgG was positive in 51 of 58 (88%) CFS patients and 24 of 68 (35%) controls. |- |'''<big class="green">+</big>''' |'''Chronic fatigue syndrome after infectious mononucleosis in adolescents''' [[Ben Katz|Ben Z Katz]], Yukiko Shiraishi, Cynthia J Mears, Helen J Binns, Renee Taylor <ref>{{Cite journal | last = Katz|first = Ben Z. | last2 = Shiraishi | first2 = Yukiko | last3 = Mears | first3 = Cynthia J. | last4 = Binns | first4 = Helen J. | last5 = Taylor | first5 = Renee | authorlink5 = Renee Taylor | date = Jul 2009 | title = Chronic fatigue syndrome after infectious mononucleosis in adolescents|url=https://pubmed.ncbi.nlm.nih.gov/19564299/|journal=Pediatrics|volume=124|issue=1|pages=189–193|doi=10.1542/peds.2008-1879|issn=1098-4275|pmc=2756827|pmid=19564299}}</ref> | 2009 | This study of 301 adolescents with infectious mononucleosis found that at 6, 12, and 24 months after mononucleosis, 13%, 7%, and 4% of these adolescents respectively met the criteria for ME/CFS. |- |'''<big class="red">−</big>''' |'''Detection of herpesviruses and parvovirus B19 in gastric and intestinal mucosa of chronic fatigue syndrome patients''' Marc Frémont, Kristine Metzger, Hamada Rady, Jan Hulstaert, Kenny De Meirleir<ref>{{Cite journal | last = Frémont | first = Marc | last2 = Metzger | first2 = Kristine | last3 = Rady | first3 = Hamada | last4 = Hulstaert | first4 = Jan | last5 = De Meirleir | first5 = Kenny | date = Mar 2009 | title = Detection of herpesviruses and parvovirus B19 in gastric and intestinal mucosa of chronic fatigue syndrome patients|url=https://pubmed.ncbi.nlm.nih.gov/19414405/|journal=In Vivo (Athens, Greece)|volume=23|issue=2|pages=209–213|issn=0258-851X|pmid=19414405}}</ref> |2009 |Stomach and duodenum biopsies using DNA PCR found only a slight increase in CFS patients that were positive for EBV compared to controls. {| class="wikitable" ! !CFS Patients !Healthy Controls |- |DNA Stomach Biopsy |10 of 48 (21%) |6 of 35 (17%) |- |DNA Duodenum Biopsy |15 of 48 (31%) |5 of 35 (15%) |} |- |'''<big class="green">+</big>''' |'''Antibody to Epstein-Barr virus deoxyuridine triphosphate nucleotidohydrolase and deoxyribonucleotide polymerase in a chronic fatigue syndrome subset''' A Martin Lerner, Maria E Ariza, Marshall Williams, Leonard Jason, Safedin Beqaj, James T Fitzgerald, Stanley Lemeshow, Ronald Glaser <ref>{{Cite journal|last = Lerner | first = A. Martin | last2 = Ariza | first2 = Maria E. | last3 = Williams | first3 = Marshall | last4 = Jason | first4 = Leonard | last5 = Beqaj | first5 = Safedin | last6 = Fitzgerald | first6 = James T. | last7 = Lemeshow | first7 = Stanley | last8 = Glaser | first8 = Ronald| date = 2012 | title = Antibody to Epstein-Barr virus deoxyuridine triphosphate nucleotidohydrolase and deoxyribonucleotide polymerase in a chronic fatigue syndrome subset|url=https://pubmed.ncbi.nlm.nih.gov/23155374/|journal=PloS One|volume=7|issue=11| pages = e47891|doi=10.1371/journal.pone.0047891|issn=1932-6203|pmc=3498272|pmid=23155374}}</ref> |2012 |This study of 20 ME/CFS patients and 20 healthy controls found 94% of patients were positive for EBV early antigen diffuse, versus 32% of the healthy controls; 44% of patients were positive for EBV dUTPase, versus 0% of the controls; 79% of patients were positive for EBV DNA polymerase, versus 0% of the controls. |- |'''<big class="red">−</big>''' |'''Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Gulf War Illness patients exhibit increased humoral responses to the Herpesviruses-encoded dUTPase: Implications in disease pathophysiology''' Peter Halpin, Marshall Vance Williams, Nancy G. Klimas, Mary Ann Fletcher, Zachary Barnes, Maria Eugenia Ariza<ref name=":5" /> |2017 |Antibodies against multiple human herpesviruses-encoded dUTPases were shown as being simultaneously produced in (30.91–52.7%) ME/CFS patients and (17.21%) of controls. EBV dUTPase antibodies were present in 16 of 55 (29%) CFS patients and 39 of 151 (26%) controls. |- |'''<big class="green">+</big>''' |'''Cytomegalovirus, Epstein‐Barr virus, and human herpesvirus‐6 infections in patients with myalgic еncephalomyelitis/chronic fatigue syndrome''' [[Evelina Shikova]], Valentina Reshkova, Аntoniya Kumanova, Sevdalina Raleva, Dora Alexandrova, Natasa Capo, Modra Murovska<ref name=":0">{{Cite journal|last = Shikova | first = Evelina | last2 = Reshkova | first2 = Valentina | last3 = Kumanova | first3 = Аntoniya | last4 = Raleva | first4 = Sevdalina | last5 = Alexandrova | first5 = Dora | last6 = Capo | first6 = Natasa | last7 = Murovska | first7 = Modra | 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=n/a|issue=n/a|doi=10.1002/jmv.25744|issn=1096-9071}}</ref> | 2020 | Study of 58 Bulgarian ME/CFS patients and 50 healthy controls found EBV DNA in the plasma of 14 of 58 (24%) patients vs. 2 of 50 (4%) controls. |} ==HHV-6 studies== HHV-6 is found in nearly 100% of adults (usually in a latent state).<ref>{{Cite journal | last = Ansari|first = Asad | last2 = Li | first2 = Shaobing | last3 = Abzug | first3 = Mark J. | last4 = Weinberg | first4 = Adriana | date = Aug 2004 | title = Human Herpesviruses 6 and 7 and Central Nervous System Infection in Children1|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3320425/|journal=Emerging Infectious Diseases|volume=10|issue=8|pages=1450–1454|doi=10.3201/eid1008.030788|issn=1080-6040|pmc=3320425|pmid=15496247}}</ref> {| class="wikitable alternance" ! scope="col" style="width: 10px;" | ! scope="col" style="width: 270px;" | Study Title ! scope="col" style="width: 32px;" | Date ! scope="col" style="Xwidth: 200px;" | Details |- |<big class="green">'''+'''</big> |'''A chronic illness characterized by fatigue, neurologic and immunologic disorders, and active human herpesvirus type 6 infection''' Dedra Buchwald, Paul R Cheney, Daniel L Peterson, Berch Henry, Susan B Wormsley, Ann Geiger, Dharam V Ablashi, S Zaki Salahuddin, Carl Saxinger, Royce Biddle, Ron Kikinis, Ferenc A Jolesz, Thomas Folks, N Balachandran, James B Peter, Robert C Gallo, Anthony L Komaroff<ref name="Buchwald1996a">{{Cite journal|last = Buchwald | first = Dedra | last2 = Cheney | first2 = Paul R. | last3 = Peterson | first3 = Daniel L. | last4 = Henry | first4 = Berch | last5 = Wormsley | first5 = Susan B. | last6 = Geiger | first6 = Ann | last7 = Ablashi | first7 = Dharam V. | last8 = Salahuddin | first8 = S. Zaki | last9 = Saxinger | first9 = CArl | date = Jan 15, 1992 | title = A chronic illness characterized by fatigue, neurologic and immunologic disorders, and active human herpesvirus type 6 infection | url =https://pubmed.ncbi.nlm.nih.gov/1309285/|journal=Annals of Internal Medicine|volume=116|issue=2|pages=103–113|doi=10.7326/0003-4819-116-2-103|issn=0003-4819|pmid=1309285}}</ref> |1992 |This study reviewed patients in the Lake Tahoe area with a chronic debilitating illness of acute onset, a portion of which were regularly bedridden or shut-in. Using lymphocyte cell culture, DNA PCR, and monoclonal antibody assay, active HHV-6 replication was found in 79 of 113 (70%) patients and 8 of 40 (20%) controls. Despite limitations of this study involving a small geographic area and relatively moderate study size, the results may be seen as significant due to the extensive analysis, and investigative measures conducted. Measurements used in the study include [[Magnetic resonance imaging|Magnetic Resonance Imaging (MRI)]], [[cerebrospinal fluid]] (CFS) analysis, standard lab testing, lymphocyte phenotyping, cell culture bioassay, and serologic testing. |- |<big class="green">'''+'''</big> |'''Prevalence of human herpesvirus 6 variants A and B in patients with chronic fatigue syndrome''' S Yalcin, H Kuratsune, K Yamaguchi, T Kitani, K Yamanishi <ref>{{Cite journal|last = Yalcin | first = S. | last2 = Kuratsune | first2 = H. | last3 = Yamaguchi | first3 = K. | last4 = Kitani | first4 = T. | last5 = Yamanishi | first5 = K. | date = 1994 | title = Prevalence of human herpesvirus 6 variants A and B in patients with chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/7968694/|journal=Microbiology and Immunology|volume=38|issue=7 | pages = 587–590|doi=10.1111/j.1348-0421.1994.tb01827.x|issn=0385-5600|pmid=7968694}}</ref> |1994 |This study examined 13 cases of ME/CFS and 13 healthy controls. In the peripheral blood mononuclear cells, HHV-6 DNA was detected in 53% of the patients, but no HHV-6 DNA was detected in the controls. Higher antibody levels to the HHV-6 late antigen were found in patients, and antibodies to HHV-6 early antigen were more prevalent in patients. |- |<big class="green">'''+'''</big> |'''Human herpesvirus 6 and human herpesvirus 7 in chronic fatigue syndrome''' D Di Luca, M Zorzenon, P Mirandola, R Colle, G A Botta, E Cassai<ref name=":8">{{Cite journal|last = Luca | first = D. Di | last2 = Zorzenon | first2 = M. | last3 = Mirandola | first3 = P. | last4 = Colle | first4 = R. | last5 = Botta | first5 = G.A. |last6 = Cassai | first6 = E. | date = 1995-06-01 | title = Human herpesvirus 6 and human herpesvirus 7 in chronic fatigue syndrome.|url=https://jcm.asm.org/content/33/6/1660|journal=Journal of Clinical Microbiology|language=en|volume=33|issue=6|pages=1660–1661|issn=0095-1137|pmid=7650209}}</ref> |1995 |This study of CFS patients and healthy controls found the presence of either HHV-6A or HHV-6B DNA by PCR in 26 of 36 (44%) CFS patients and 7 of 24 (29%) controls; and found HHV-6A DNA in 8 of 36 (22%) patients and 1 of 24 (4%) controls. |- |<big class="green">'''+'''</big> |'''Prevalence of IgM antibodies to human herpesvirus 6 early antigen (p41/38) in patients with chronic fatigue syndrome''' M Patnaik, A L Komaroff, E Conley, E A Ojo-Amaize, J B Peter<ref>{{Cite journal | last = Patnaik|first = M. | last2 = Komaroff | first2 = A.L. | last3 = Conley | first3 = E. | last4 = Ojo-Amaize | first4 = E.A. | last5 = Peter | first5 = J.B. | date = Nov 1995 | title = Prevalence of IgM antibodies to human herpesvirus 6 early antigen (p41/38) in patients with chronic fatigue syndrome|url=https://pubmed.ncbi.nlm.nih.gov/7594679/|journal=The Journal of Infectious Diseases|volume=172|issue=5|pages=1364–1367|doi=10.1093/infdis/172.5.1364|issn=0022-1899|pmid=7594679}}</ref> |1995 |Fairly large study using 2 geographically separate groups of patients to evaluate the possible association of HHV-6 infection with chronic fatigue syndrome (CFS). Methods involved prevalence of IgG and IgM antibodies against HHV-6 early antigen (EA), perhaps indicating active replication. Elevated HHV-6 EA-specific IgG or IgM antibody titers were found in 119 of 154 (77%) CFS patients and 20 of 165 (12%) controls. |- |<big class="green">'''+'''</big> |'''Viral serologies in patients with chronic fatigue and chronic fatigue syndrome''' Dedra Buchwald, Rhoda L. Ashley, Tsilke Pearlman, Phalla Kith, and Anthony L. Komaroff<ref name="Buchwald1996a" /> |1996 |Large study was performed on CFS patients and healthy control subjects to compare antibodies to various viruses. HHV-6 virus antibody IgG were ≥12,800 in 39 of 295 (13%) CFS patients and 2 of 30 (7%) controls. |- |<big class="red">'''−'''</big> |'''Human Herpesviruses in Chronic Fatigue Syndrome''' Howard L. Wallace, II, Benjamin Natelson, William Gause, John Hay<ref name=":6">{{Cite journal|last = Wallace | first = Howard L. | last2 = Natelson | first2 = Benjamin | last3 = Gause | first3 = William | last4 = Hay | first4 = John | date = Mar 1999 | title = Human Herpesviruses in Chronic Fatigue Syndrome|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC95690/|journal=Clinical and Diagnostic Laboratory Immunology|volume=6|issue=2|pages=216–223|issn=1071-412X|pmid=10066657}}</ref> |1999 |This study of civilian and Persian Gulf War veterans found HHV-6 DNA in the peripheral blood of 26 of 74 (35%) CFS patients and 19 of 71 (27%) controls. |- |<big class="red">'''−'''</big> |'''Human herpesviruses 6 and 7 in chronic fatigue syndrome: a case-control study''' W C Reeves, F R Stamey, J B Black, A C Mawle, J A Stewart, P E Pellett<ref name=":7" /> |2000 |Study on infection association of human herpesvirus (HHV) 6A, HHV-6B, or HHV-7 between ME/CFS patients and healthy controls. HHV-6 DNA was found in 3 of 26 (12%) patients and 15 of 50 (28%) controls. |- |<big class="green">'''+'''</big> |'''Frequent HHV-6 reactivation in multiple sclerosis (MS) and chronic fatigue syndrome (CFS) patients''' D V Ablashi, H B Eastman, C B Owen, M M Roman, J Friedman, J B Zabriskie, D L Peterson, G R Pearson, J E Whitman<ref>{{Cite journal | last = Ablashi|first = D.V. | last2 = Eastman | first2 = H.B. | last3 = Owen | first3 = C.B. | last4 = Roman | first4 = M.M. | last5 = Friedman | first5 = J. | last6 = Zabriskie | first6 = J.B. | last7 = Peterson | first7 = D.L. | last8 = Pearson | first8 = G.R. | last9 = Whitman | first9 = J.E. | date = May 2000 | title = Frequent HHV-6 reactivation in multiple sclerosis (MS) and chronic fatigue syndrome (CFS) patients|url=https://pubmed.ncbi.nlm.nih.gov/10738137/|journal=Journal of Clinical Virology: The Official Publication of the Pan American Society for Clinical Virology|volume=16|issue=3|pages=179–191|doi=10.1016/s1386-6532(99)00079-7|issn=1386-6532|pmid=10738137}}</ref> |2000 |This study of 35 ME/CFS patients and 25 healthy controls found higher levels of HHV-6 Early Antigen (EA) IgM antibody in 54% of patients versus 8% of controls; and found EA IgG in 66% of patients versus 20% of controls. |- |<big class="green">'''+'''</big> |'''Multiple co-infections (Mycoplasma, Chlamydia, human herpes virus-6) in blood of chronic fatigue syndrome patients: association with signs and symptoms''' G L Nicolson, R Gan, J Haier<ref>{{Cite journal|last = Nicolson | first = G.L. | last2 = Gan | first2 = R. | last3 = Haier | first3 = J. | date = May 2003 | title = Multiple co-infections (Mycoplasma, Chlamydia, human herpes virus-6) in blood of chronic fatigue syndrome patients: association with signs and symptoms|url=https://pubmed.ncbi.nlm.nih.gov/12887507/|journal=APMIS: acta pathologica, microbiologica, et immunologica Scandinavica|volume=111|issue=5 | pages = 557–566|doi=10.1034/j.1600-0463.2003.1110504.x|issn=0903-4641|pmid=12887507}}</ref> |2003 |This fairly large study used polymerase chain reaction (PCR) in an attempt to show evidence of active human herpes virus-6 (HHV-6) infections, as well as [[Mycoplasma]] and [[Chlamydophila pneumoniae|Chlamydia Pneumoniae]] infections in CFS patients. HHV-6 DNA was detected in 61 of 200 (31%) CFS patients and 9 of 100 (9%) healthy controls. While none of the controls had co-infections, multiple co-infections found in CFS patients included multiple Mycoplasmal infections (22%), HHV-6 + Mycoplasma (16%), C. pneumoniae + Mycoplasma (4%), and C. pneumoniae + HHV-6 (2.5%). |- |<big class="red">'''−'''</big> |'''Detection of Herpesviruses and Parvovirus B19 in Gastric and Intestinal Mucosa of Chronic Fatigue Syndrome Patients''' Marc Frémont, Kristine Metzger, Hamada Rady, Jan Hulstaert, Kenny De Meirleir<ref name=":2">{{Cite journal | last = Frémont | first = Marc | last2 = Metzger | first2 = Kristine | last3 = Rady | first3 = Hamada | last4 = Hulstaert | first4 = Jan | last5 = De Meirleir | first5 = Kenny | date = Mar 2009 | title = Detection of herpesviruses and parvovirus B19 in gastric and intestinal mucosa of chronic fatigue syndrome patients|url=https://pubmed.ncbi.nlm.nih.gov/19414405/|journal=In Vivo (Athens, Greece)|volume=23|issue=2|pages=209–213|issn=0258-851X|pmid=19414405}}</ref> |2009 |A study to investigate the presence of HHV-6, HHV-7, EBV and parvovirus B19 in the gastro-intestinal tract of CFS patients found HHV-6 stomach biopsy DNA in 15 of 48 (31%) CFS patients and 10 of 35 (29%) controls. |- |<big class="green">'''+'''</big> |'''Association of Active Human Herpesvirus-6, -7 and Parvovirus B19 Infection with Clinical Outcomes in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome''' Svetlana Chapenko, Angelika Krumina, Inara Logina, Santa Rasa, Maksims Chistjakovs, Alina Sultanova, Ludmila Viksna, Modra Murovska<ref name=":3">{{Cite web|url=https://pubmed.ncbi.nlm.nih.gov/22927850/ | title = Association of Active Human Herpesvirus-6, -7 and Parvovirus B19 Infection with Clinical Outcomes in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome|last = Chapenko|first = Svetlana | last2 = Krumina | first2 = Angelika | date = 2012-08-13 | website = Advances in Virology|language=en|access-date=2020-08-20 | last3 = Logina | first3 = Inara | last4 = Rasa | first4 = Santa | last5 = Chistjakovs | first5 = Maksims | last6 = Sultanova | first6 = Alina | last7 = Viksna | first7 = Ludmila | last8 = Murovska | first8 = Modra | authorlink= | authorlink2 = |archive-url=|archive-date=|url-status=}}</ref> |2012 |This study of 108 ME/CFS patients and 90 healthy controls found HHV-6 DNA in plasma samples of 16 of 108 (15%) ME/CFS patients and 0 of 90 (0%) healthy controls. Of the 16 HHV-6 positive CFS patients, 14 of 16 were co-infections with HHV-7 and/or Parvovirus B19, where only 2 of 16 were single HHV-6 infections.<ref name=":4">{{Cite web|url=https://www.hindawi.com/journals/av/2012/205085/tab1/ | title = Table 1 {{!}} Association of Active Human Herpesvirus-6, -7 and Parvovirus B19 Infection with Clinical Outcomes in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome | website = hindawi.com|access-date=2020-08-20}}</ref> |- |<big class="green">'''+'''</big> |'''Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Gulf War Illness patients exhibit increased humoral responses to the Herpesviruses-encoded dUTPase: Implications in disease pathophysiology''' Peter Halpin, Marshall Vance Williams, Nancy G. Klimas, Mary Ann Fletcher, Zachary Barnes, Maria Eugenia Ariza<ref name=":5">{{Cite journal|last = Halpin | first = Peter | last2 = Williams | first2 = Marshall Vance | last3 = Klimas | first3 = Nancy G. | last4 = Fletcher | first4 = Mary Ann | last5 = Barnes | first5 = Zachary | last6 = Ariza | first6 = Maria Eugenia | date = Sep 2017 | title = Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Gulf War Illness patients exhibit increased humoral responses to the Herpesviruses-encoded dUTPase: Implications in disease pathophysiology|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5513753/|journal=Journal of medical virology|volume=89|issue=9|pages=1636–1645|doi=10.1002/jmv.24810|issn=0146-6615|pmc=5513753|pmid=28303641}}</ref> |2017 |A study surrounding the involvement of herpesvirus as a possible trigger for ME/CFS as well as the involvement of herpesvirus in the pathophysiology of Gulf War Illness (GWI) patients. A separate set of healthy controls were used for comparison and matched to ME/CFS and GWI cases by age, gender, and race/ethnicity. Antibodies against multiple human herpesviruses-encoded dUTPases were shown as being simultaneously produced in (30.91–52.7%) ME/CFS patients and (17.21%) of controls. HHV-6 dUTPase antibodies were present in 29 of 55 (53%) CFS patients and 45 of 151 (30%) controls. |- |<big class="green">'''+'''</big> |'''Cytomegalovirus, Epstein‐Barr virus, and human herpesvirus‐6 infections in patients with myalgic еncephalomyelitis/chronic fatigue syndrome''' Evelina Shikova, Valentina Reshkova, Аntoniya Kumanova, Sevdalina Raleva, Dora Alexandrova, Natasa Capo, Modra Murovska<ref name=":0" /> | 2020 | Study of 58 Bulgarian ME/CFS patients and 50 healthy controls found HHV-6 DNA in the plasma of 1 of 58 (1.7%) patients vs. 0 of 50 (0%) controls. |} ==Cytomegalovirus studies== Cytomegalovirus is found in 58% of adults (usually in a latent state).<ref>{{Cite journal|last = Dollard | first = Sheila C. | last2 = Staras | first2 = Stephanie A.S. | last3 = Amin | first3 = Minal M. | last4 = Schmid | first4 = D. Scott | last5 = Cannon | first5 = Michael J. | date = Nov 2011 | title = National prevalence estimates for cytomegalovirus IgM and IgG avidity and association between high IgM antibody titer and low IgG avidity|url=https://pubmed.ncbi.nlm.nih.gov/21918114/|journal=Clinical and vaccine immunology: CVI|volume=18|issue=11|pages=1895–1899|doi=10.1128/CVI.05228-11|issn=1556-679X|pmc=3209034|pmid=21918114}}</ref> Cytomegalovirus is a rarer cause of mononucleosis. {| class="wikitable alternance" ! scope="col" style="width: 10px;" | ! scope="col" style="width: 270px;" | Study Title ! scope="col" style="width: 32px;" | Date ! scope="col" style="Xwidth: 200px;" | Details |- |<big class="red">'''−'''</big> |'''Viral serologies in patients with chronic fatigue and chronic fatigue syndrome''' Dedra Buchwald, Rhoda L. Ashley, Tsilke Pearlman, Phalla Kith, and Anthony L. Komaroff<ref name="Buchwald1996b" /> |1996 |Large study was performed on CFS patients and healthy control subjects to compare antibodies to various viruses. Cytomegalovirus (CMV) antibody IgG were > 2,048 in 9 of 285 (3%) CFS patients and 1 of 30 (3%) controls. |- |<big class="green">'''+'''</big> |'''Cytomegalovirus, Epstein‐Barr virus, and human herpesvirus‐6 infections in patients with myalgic еncephalomyelitis/chronic fatigue syndrome''' Evelina Shikova, Valentina Reshkova, Аntoniya Kumanova, Sevdalina Raleva, Dora Alexandrova, Natasa Capo, Modra Murovska<ref name=":0" /> | 2020 | Study of 58 Bulgarian ME/CFS patients and 50 healthy controls found CMV DNA in the plasma of 2 of 58 (3.4%) patients vs. 0 of 50 (0%) controls. |} == Varicella zoster virus studies== Varicella zoster virus (VZV) is found in 88% of the adult population (usually in a latent state).<ref>{{Cite journal | last = Fatha | first = Noorul | last2 = Ang | first2 = Li Wei | last3 = Goh | first3 = Kee Tai | date = May 2014 | title = Changing seroprevalence of varicella zoster virus infection in a tropical city state, Singapore|url=https://pubmed.ncbi.nlm.nih.gov/24269652/|journal=International journal of infectious diseases: IJID: official publication of the International Society for Infectious Diseases|volume=22 | pages = 73–77|doi=10.1016/j.ijid.2013.10.003|issn=1878-3511|pmid=24269652}}</ref> It causes chickenpox and shingles. {| class="wikitable alternance" ! scope="col" style="width: 10px;" | ! scope="col" style="width: 270px;" | Study Title ! scope="col" style="width: 32px;" | Date ! scope="col" style="Xwidth: 200px;" | Details |- |<big class="red">'''−'''</big> |'''Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Gulf War Illness patients exhibit increased humoral responses to the Herpesviruses-encoded dUTPase: Implications in disease pathophysiology''' Peter Halpin, Marshall Vance Williams, Nancy G. Klimas, Mary Ann Fletcher, Zachary Barnes, Maria Eugenia Ariza<ref name=":5" /> |2017 |A study surrounding the involvement of herpesvirus as a possible trigger for ME/CFS as well as the involvement of herpesvirus in the pathophysiology of Gulf War Illness (GWI) patients. A separate set of healthy controls were used for comparison and matched to ME/CFS and GWI cases by age, gender, and race/ethnicity. Varicella-zoster virus (VZV) dUTPase antibodies were present in 2 of 55 (4%) CFS patients and 13 of 151 (9%) controls. |} == Herpes simplex virus studies== Herpes simplex virus I is found in 54% of adults, and herpes simplex virus II in 16% of adults (usually in a latent state).<ref name="Bradley2014">{{Cite journal|last = Bradley|first = Heather | last2 = Markowitz | first2 = Lauri E. | last3 = Gibson | first3 = Theda | last4 = McQuillan | first4 = Geraldine M. | date = 2014-02-01 | title = Seroprevalence of herpes simplex virus types 1 and 2--United States, 1999-2010|url=https://pubmed.ncbi.nlm.nih.gov/24136792/|journal=The Journal of Infectious Diseases|volume=209|issue=3 | pages = 325–333|doi=10.1093/infdis/jit458|issn=1537-6613|pmid=24136792}}</ref> HSV causes oral mouth sores. {| class="wikitable alternance" ! scope="col" style="width: 10px;" | ! scope="col" style="width: 270px;" | Study Title ! scope="col" style="width: 32px;" | Date ! scope="col" style="Xwidth: 200px;" | Details |- |<big class="green">'''+'''</big> |'''Antibodies to Herpes Simplex Types 1 and 2 in Chronic Fatigue Syndrome''' PA Bond & TG Dinan<ref name="Bond2006">{{Cite journal|last = Bond | first = P.A. | last2 = Dinan | first2 = T.G. | date = 2006-01-01 | title = Antibodies to Herpes Simplex Types 1 and 2 in Chronic Fatigue Syndrome|url=https://doi.org/10.1300/J092v13n01_04|journal=Journal of Chronic Fatigue Syndrome|volume=13|issue=1 | pages = 35–40|doi=10.1300/J092v13n01_04|issn=1057-3321}}</ref> | 2011 | This study of 27 ME/CFS patients and 26 healthy controls found HSV I antibodies in 74% of patients versus 42% of controls; and found HSV II antibodies in 70% of patients versus 31% of controls. |- |<big class="red">'''−'''</big> |'''Antibodies to Human Herpesviruses in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients''' Blomberg et al.<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> | 2019 | This study of patients meeting the [[Canadian Consensus Criteria]] for ME/CFS and/or the ACR 1990 criteria for [[fibromyalgia]] found that levels of antibodies to HSV-1 and HSV-2 were similar or slightly lower in ME/CFS patients and fibromyalgia patients compared to healthy blood donors. |} == HHV-7 studies== HHV-7 is found in more than 95% of the adult population (usually in a latent state).<ref>{{Cite journal|last = Clark|first = D.A. | last2 = Freeland | first2 = M.L. | last3 = Mackie | first3 = L.K. | last4 = Jarrett | first4 = R.F. | last5 = Onions | first5 = D.E. | date = Jul 1993 | title = Prevalence of antibody to human herpesvirus 7 by age|url=https://pubmed.ncbi.nlm.nih.gov/8390545/|journal=The Journal of Infectious Diseases|volume=168|issue=1|pages=251–252|doi=10.1093/infdis/168.1.251|issn=0022-1899|pmid=8390545}}</ref> {| class="wikitable alternance" ! scope="col" style="width: 10px;" | ! scope="col" style="width: 270px;" | Study Title ! scope="col" style="width: 32px;" | Date ! scope="col" style="Xwidth: 200px;" | Details |- |<big class="red">'''−'''</big> |'''Human herpesvirus 6 and human herpesvirus 7 in chronic fatigue syndrome''' D Di Luca, M Zorzenon, P Mirandola, R Colle, G A Botta, E Cassai<ref name=":8" /> |1995 |This study of CFS patients and healthy controls found the presence of HHV-7 DNA by PCR in 23 of 28 (82%) CFS patients and 20 of 24 (83%) controls. |- |<big class="red">'''−'''</big> |'''Human Herpesviruses in Chronic Fatigue Syndrome''' Howard L. Wallace, II, Benjamin Natelson, William Gause, John Hay<ref name=":6" /> |1999 |This study of civilian and Persian Gulf War veterans found HHV-7 DNA in the peripheral blood of 58 of 75 (77%) CFS patients and 51 of 73 (70%) controls. |- |<big class="red">'''−'''</big> |'''Human herpesviruses 6 and 7 in chronic fatigue syndrome: a case-control study''' W C Reeves, F R Stamey, J B Black, A C Mawle, J A Stewart, P E Pellett<ref name=":7">{{Cite journal|last = Reeves | first = W.C. | last2 = Stamey | first2 = F.R. | last3 = Black | first3 = J.B. | last4 = Mawle | first4 = A.C. | last5 = Stewart | first5 = J.A. |last6 = Pellett | first6 = P.E. | date = Jul 2000 | title = Human herpesviruses 6 and 7 in chronic fatigue syndrome: a case-control study|url=https://pubmed.ncbi.nlm.nih.gov/10913395/|journal=Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America|volume=31|issue=1 | pages = 48–52|doi=10.1086/313908|issn=1058-4838|pmid=10913395}}</ref> |2000 |Study on infection association of human herpesvirus (HHV) 6A, HHV-6B, or HHV-7 between ME/CFS patients and healthy controls. HHV-7 DNA was found in 2 of 26 (8%) patients and 12 of 50 (25%) controls. |- |<big class="red">'''−'''</big> |'''Detection of Herpesviruses and Parvovirus B19 in Gastric and Intestinal Mucosa of Chronic Fatigue Syndrome Patients''' Marc Frémont, Kristine Metzger, Hamada Rady, Jan Hulstaert, Kenny De Meirleir<ref name=":2" /> |2009 |A study to investigate the presence of HHV-6, HHV-7, EBV and parvovirus B19 in the gastro-intestinal tract of CFS patients found HHV-7 stomach biopsy DNA in 44 of 48 (92%) CFS patients and 29 of 35 (83%) controls. |- |<big class="green">'''+'''</big> |'''Association of Active Human Herpesvirus-6, -7 and Parvovirus B19 Infection with Clinical Outcomes in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome''' Svetlana Chapenko, Angelika Krumina, Inara Logina, Santa Rasa, Maksims Chistjakovs, Alina Sultanova, Ludmila Viksna, Modra Murovska<ref name=":3" /> |2012 |This study of 108 ME/CFS patients and 90 healthy controls found HHV-7 DNA in plasma samples of 57 of 108 (53%) ME/CFS patients and 10 of 90 (11%) healthy controls. Of the 57 HHV-7 positive CFS patients, 29 of 57 were co-infections with HHV-6 and/or Parvovirus B19, where only 28 of 57 were single HHV-7 infections.<ref name=":4" /> |} == See also == * [[Cytomegalovirus]] * [[Epstein-Barr virus]] * [[Herpes simplex virus]] * [[Human herpesvirus 6]] * [[Human herpesvirus 7]] * [[List of enterovirus infection studies]] * [[Varicella zoster virus]] * [[Abortive infection theory of ME/CFS]] (Dr Lerner's theory that abortive herpesviruses cause ME/CFS) == Learn more == * [https://hhv-6foundation.org HHV-6 Foundation] ==References== {{Reflist}} [[Category:Lists]] [[Category:Virology]]
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