PROJECT SUMMARY / ABSTRACT
Our research project, entitled “Human Herpesvirus 6B in Myalgic Encephalomyelitis / Chronic Fatigue Syndrome
pathogenesis: temporal analysis of viral reactivation and immunity to elucidate cause vs effect”, aims to validate
or refute the findings of our preliminary study on the role of human herpesviruses on the severity of symptoms
in ME/CFS, and to determine if the virus reactivation is a cause or a consequence of the immune dysregulation.
We will follow-up a larger number of consenting individuals (n=306), using our rigorous protocols designed to
recruit participants to the UK ME/CFS Biobank (UKMEB). We have consent to re-contact UKMEB participants
with ME/CFS (including those with a severe form of disease), and non-diseased controls (n=>500), with clinical
assessments and collection of biosamples (blood and saliva). We will also recruit another comparison group,
consisting of people with Long-COVID presenting with symptoms typical of ME/CFS (n=30), as well as people
who did not develop long-term post-acute sequelae of COVID-19 after acute illness (Short COVID: n=30). The
study population will comprise individuals from 18 - 60 years old, who have a diagnosis for ME/CFS or Long
COVID with ME/CFS, as well as healthy controls and people who had Short COVID, in compliance with inclusion
and exclusion criteria.
We will perform a longitudinal analysis of people living with ME/CFS to determine the association and temporal
relationship between HHV-6B DNA concentration and ME/CFS symptom severity, measuring viral DNA in saliva
monthly for 6 months, alongside symptom scoring. To confirm that increases in HHV-6B DNA in saliva reflect
systemic reactivation, we will measure blood viral RNA, DNA and protein, with the hypothesis that saliva RNA
will correlate with saliva DNA concentration, and that all will increase together when ME/CFS symptoms are
elevated. We will also measure frequency, phenotype and function of HHV-6B-reactive CD4+ and CD8+ T cells
in people with ME/CFS. using flow cytometry, and will investigate the immunosuppressive effects of HHV-6B on
antigen presentation in macrophages in ME/CFS using gene expression analysis. We hypothesize that HHV-
6B-specific T cells expand as ME/CFS symptoms worsen but are ineffective in for HHV-6B control, and we will
test whether similar changes are observed in those with Long COVID in people who fulfill the diagnostic criteria
for ME/CFS.
Our goal, which stems from our successful pilot study, is to establish whether HHV-6B reactivation is causal in
ME/CFS pathogenesis, and generate biological evidence which will inform targeted interventions such as
vaccine development.
