List of herpesvirus infection studies

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 + symbol, whereas negative studies (finding no significant difference in prevalence between patients and healthy controls) are indicated by the − symbol.

Epstein-Barr virus studies

Epstein-Barr virus (EBV) is found in 95% of the adult population (usually in a latent state), and is the most common cause of mononucleosis.

	Study Title	Date	Details
+	Chronic fatigue syndrome: clinical condition associated with immune activation A L Landay, C Jessop, E T Lennette, J A Levy	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.
+	Persistent virus infection of muscle in postviral fatigue syndrome L Cunningham, N E Bowles, L C Archard	1991	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.
+	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	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.
−	Viral serologies in patients with chronic fatigue and chronic fatigue syndrome Dedra Buchwald, Rhoda L. Ashley, Tsilke Pearlman, Phalla Kith, and Anthony L. Komaroff	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. 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%)
+	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	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.
+	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	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.
+	Chronic fatigue syndrome after infectious mononucleosis in adolescents Ben Z Katz, Yukiko Shiraishi, Cynthia J Mears, Helen J Binns, Renee Taylor	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.
−	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	2009	Stomach and duodenum biopsies using DNA PCR found only a slight increase in CFS patients that were positive for EBV compared to controls. 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%)
+	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	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.
−	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	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.
+	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	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).

	Study Title	Date	Details
+	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	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 (MRI), cerebrospinal fluid (CFS) analysis, standard lab testing, lymphocyte phenotyping, cell culture bioassay, and serologic testing.
+	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	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.
+	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	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.
+	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	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.
+	Viral serologies in patients with chronic fatigue and chronic fatigue syndrome Dedra Buchwald, Rhoda L. Ashley, Tsilke Pearlman, Phalla Kith, and Anthony L. Komaroff	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.
−	Human Herpesviruses in Chronic Fatigue Syndrome Howard L. Wallace, II, Benjamin Natelson, William Gause, John Hay	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.
−	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	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.
+	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	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.
+	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	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 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%).
−	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	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.
+	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	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.
+	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	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.
+	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	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). Cytomegalovirus is a rarer cause of mononucleosis.

	Study Title	Date	Details
−	Viral serologies in patients with chronic fatigue and chronic fatigue syndrome Dedra Buchwald, Rhoda L. Ashley, Tsilke Pearlman, Phalla Kith, and Anthony L. Komaroff	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.
+	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	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). It causes chickenpox and shingles.

	Study Title	Date	Details
−	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	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). HSV causes oral mouth sores.

	Study Title	Date	Details
+	Antibodies to Herpes Simplex Types 1 and 2 in Chronic Fatigue Syndrome PA Bond & TG Dinan	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.
−	Antibodies to Human Herpesviruses in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients Blomberg et al.	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).

	Study Title	Date	Details
−	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	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.
−	Human Herpesviruses in Chronic Fatigue Syndrome Howard L. Wallace, II, Benjamin Natelson, William Gause, John Hay	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.
−	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	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.
−	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	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.
+	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	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.

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

• HHV-6 Foundation

See myalgic encephalomyelitis.

See chronic fatigue syndrome.

antibodies Antibody/immunoglobulin refers to any of a large number of specific proteins produced by B cells that act against an antigen in an immune response.

antibodies Antibody/immunoglobulin refers to any of a large number of specific proteins produced by B cells that act against an antigen in an immune response.

enterovirus A genus of RNA viruses which typically enter the body through the respiratory or gastrointestinal systems and sometimes spread to the central nervous system or other parts of the body, causing neurological, cardiac, and other damage. Since the first reports of myalgic encephalomyelitis (ME), enteroviruses have been suspected as a cause of ME. Enteroviruses have also been implicated as the cause of Type I diabetes, congestive heart failure, and other conditions. Enteroviruses include poliovirus, coxsackieviruses, and many others. New enteroviruses and new strains of existing enteroviruses are continuously being discovered. (Learn more: viralzone.expasy.org)

antibodies Antibody/immunoglobulin refers to any of a large number of specific proteins produced by B cells that act against an antigen in an immune response.

The clear yellowish fluid that remains from blood plasma after clotting factors have been removed by clot formation. (Blood plasma is simply blood that has had its blood cells removed.)

serum The clear yellowish fluid that remains from blood plasma after clotting factors have been removed by clot formation. (Blood plasma is simply blood that has had its blood cells removed.)

antibodies Antibody/immunoglobulin refers to any of a large number of specific proteins produced by B cells that act against an antigen in an immune response.

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.

antibodies Antibody/immunoglobulin refers to any of a large number of specific proteins produced by B cells that act against an antigen in an immune response.

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.

1. (verb) analysis (as of an ore or drug) to determine the presence, absence, or quantity of one or more components. 2. (noun) In biochemistry, any laboratory protocol used to test a sample for one or more qualities.

assay 1. (verb) analysis (as of an ore or drug) to determine the presence, absence, or quantity of one or more components. 2. (noun) In biochemistry, any laboratory protocol used to test a sample for one or more qualities.

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.