Tag: HHV-6B

Salivary DNA loads for human herpes viruses 6 and 7 are correlated with disease phenotype in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome

Abstract:

Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS) is a complex chronic condition affecting multiple body systems, with unknown cause, unclear pathogenesis mechanisms, and fluctuating symptoms which may lead to severe debilitation. It is frequently reported to have been triggered by an infection, particularly with herpes virus family members; however, there are no clear differences in exposure to, or seroprevalence of, any herpes virus in people with ME/CFS and healthy individuals. Herpes viruses exist in lytic and latent forms, and it is possible that ME/CFS is associated with viral reactivation, which has not been detectable previously due to insensitive testing methods.

Saliva samples were collected from 30 people living with ME/CFS at monthly intervals for six months and at times when they experienced symptom exacerbation, as well as from 14 healthy control individuals. The viral DNA load of the nine human herpes viruses was determined by digital droplet PCR. Symptoms were assessed by questionnaire at each time point.

Human herpes virus (HHV) 6B, HHV-7, herpes simplex virus 1 and Epstein Barr virus were detectable within the saliva samples, with higher HHV-6B and HHV-7 viral loads detected in people with ME/CFS than in healthy controls. Participants with ME/CFS could be broadly separated into two groups: one group displayed fluctuating patterns of herpes viruses detectable across the six months while the second group displayed more stable viral presentation. In the first group, there was positive correlation between HHV-6B and HHV-7 viral load and severity of symptom scores, including pain, neurocognition and autonomic dysfunction.

The results indicate that fluctuating viral load, related to herpesvirus reactivation state, may play a role in ME/CFS pathogenesis, or might be a consequence of dysregulated immune function. The sampling strategy and molecular tools developed permit large-scale epidemiological investigations.

Contribution to the Field The cause of ME/CFS and the mechanisms underlying disease pathogenesis are not known, although symptoms are often triggered by infection. Human herpes virus (HHV) family members have been implicated, although there is no difference in the seroprevalence of any HHV in people with ME/CFS and healthy controls, showing there is similar prior infection rate. HHVs exist in either latent or active, lytic, phases in the human host, and it is possible that ME/CFS symptoms and their severity is related to HHV reactivation from a latent state. We have used droplet digital PCR, a sensitive and specific method, to measure the prevalence and DNA concentration of HHVs in the saliva of people with ME/CFS and controls, and analysed the correlation with disease over a six-month timecourse. We found that two HHVs, HHV-7 and HHV-6B, were elevated in saliva from people with ME/CFS, and that in people who were severely affected by ME/CFS, the concentration HHV DNA correlated with symptom severity over time in a subgroup of patients with fluctuating salivary HHV repertoire. Our study demonstrates the feasibility of measuring HHV concentration in readily acquired samples, enabling future large-scale studies aimed at testing the causal role of HHV reactivation in ME/CFS disease.

Source: Ji-Sook Lee, Eliana M. Lacerda, Luis Nacul, Caroline C. Kingdon, Jasmin Norris, Shennae O’Boyle, Chrissy H. Roberts, Luigi Palla, Eleanor M. Riley, Jacqueline M. Cliff. Salivary DNA loads for human herpes viruses 6 and 7 are correlated with disease phenotype in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome.
medRxiv 2021.01.06.20248486; doi: https://doi.org/10.1101/2021.01.06.20248486 https://www.medrxiv.org/content/10.1101/2021.01.06.20248486v1.full-text  (Full text)

No serological evidence for a role of HHV-6 infection in chronic fatigue syndrome

Abstract:

Human herpesvirus 6A (HHV-6A) and human herpesvirus 6B (HHV-6B) are associated with a variety of conditions including rash, fever, and encephalitis and may play a role in several neurological diseases. Here luciferase immunoprecipitation systems (LIPS) was used to develop HHV-6 serologic diagnostic tests using antigens encoded by the U11 gene from HHV-6A (p100) and HHV-6B (p101).

Analysis of the antibody responses against Renilla luciferase fusions with different HHV-6B p101 fragments identified an antigenic fragment (amino acids 389 to 858) that demonstrated ~86% seropositivity in serum samples from healthy US blood donors. Additional experiments detected a HHV-6A antigenic fragment (amino acids 751-870) that showed ~48% antibody seropositivity in samples from Mali, Africa, a known HHV-6A endemic region. In contrast to the high levels of HHV-6A immunoreactivity seen in the African samples, testing of US blood donors with the HHV-6A p100 antigenic fragment revealed little immunoreactivity.

To potentially explore the role of HHV-6 infection in human disease, a blinded cohort of controls (n=59) and chronic fatigue syndrome (CFS) patients (n=72) from the US was examined for serum antibodies. While only a few of the controls and CFS patients showed high level immunoreactivity with HHV-6A, a majority of both the controls and CFS patients showed significant immunoreactivity with HHV-6B. However, no statistically significant differences in antibody levels or frequency of HHV-6A or HHV-6B infection were detected between the controls and CFS patients. These findings highlight the utility of LIPS for exploring the seroepidemiology of HHV-6A and HHV-6B infection, but suggest that these viruses are unlikely to play a role in the pathogenesis of CFS.

 

Source: Burbelo PD, Bayat A, Wagner J, Nutman TB, Baraniuk JN, Iadarola MJ. No serological evidence for a role of HHV-6 infection in chronic fatigue syndrome. Am J Transl Res. 2012;4(4):443-51. Epub 2012 Oct 10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3493030/ (Full article)

 

Sensitive, qualitative detection of human herpesvirus-6 and simultaneous differentiation of variants A and B

Abstract:

BACKGROUND: The current limitations of laboratory testing for the detection of human herpesvirus virus 6 (HHV-6) in clinical specimens with low HHV-6 viral loads make this area a priority for further research and development.

OBJECTIVES: To develop and validate a sensitive qualitative assay for simultaneous HHV-6 detection and variant differentiation.

METHODS: We developed a diagnostic procedure, which combines a magnetic bead-based nucleic acid extraction, PCR amplification, and colorimetric microtiter plate identification (MAG-PCR-EIA), for the sensitive detection of HHV-6 and the simultaneous differentiation of HHV-6A and HHV-6B.

RESULTS: Analytic sensitivities of the MAG-PCR-EIA assay were 10 copies per reaction for both HHV-6A and HHV-6B variants, which is equivalent to 20 copies/ml when 1ml of clinical specimen was processed. A proficiency panel containing 11 blinded specimens covering HHV-6A viral loads from 0 to 100,000 copies was tested, and the MAG-PCR-EIA was able to detect the lowest concentration at one copy in 200microl. A panel of 27 urine specimens, which were collected from patients with and without chronic fatigue syndrome, was tested by the MAG-PCR-EIA. HHV-6 was detected in two (HHV-6A) patients who have chromosomally integrated HHV-6A and in one (HHV-6B) patient who was a healthy control and diagnosed as cervical cancer later on. The HHV-6 results did not correlate with results previously determined by HHV-6 antigenemia in urine.

CONCLUSION: With large specimen volumes processed and an additional signal amplification incorporated, the MAG-PCR-EIA provides a sensitive and qualitative system for HHV-6 detection and simultaneous variant differentiation. Clinical relevance of the assay awaits further investigation.

 

Source: Li H, Meng S, Levine SM, Stratton CW, Tang YW. Sensitive, qualitative detection of human herpesvirus-6 and simultaneous differentiation of variants A and B. J Clin Virol. 2009 Sep;46(1):20-3. doi: 10.1016/j.jcv.2009.05.016. Epub 2009 Jun 21. https://www.ncbi.nlm.nih.gov/pubmed/19540801

 

Human herpesvirus 6 and human herpesvirus 7 in chronic fatigue syndrome

Abstract:

We analyzed lymphocytes of patients with chronic fatigue syndrome (CFS) for the presence of human herpesvirus 6 (HHV-6) and HHV-7 DNA. HHV-7 was present in over 80% of CFS patients and healthy controls, while the prevalence of HHV-6 variant A increased significantly in CFS cases (22 versus 4%; P = 0.05).

 

Source: Di Luca D, Zorzenon M, Mirandola P, Colle R, Botta GA, Cassai E. Human herpesvirus 6 and human herpesvirus 7 in chronic fatigue syndrome. J Clin Microbiol. 1995 Jun;33(6):1660-61. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC228240/pdf/331660.pdf (Full article)