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Principal Investigator: Jackie Cliff
Organization: LONDON SCH/HYGIENE & TROPICAL MEDICINE
Fiscal Year: 2024
Award: $510,930
Funding agency: National Institute of Allergy and Infectious Diseases
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.
Terms: <(TNF)-α><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><21+ years old><Active Follow-up><Acute><Adult><Adult Human><Affect><Antigen Presentation><Antigen-Presenting Cells><Assay><Bacterial Infections><Bioassay><Biological><Biological Assay><Blood><Blood Reticuloendothelial System><Blood Sample><Blood monocyte><Blood specimen><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><COVID-19><COVID-19 virus><COVID19 virus><CV-19><Cachectin><Causality><Cell Body><Cell Function><Cell Physiology><Cell Process><Cells><Cellular Function><Cellular Physiology><Cellular Process><Characteristics><Chemical Exposure><Chronic Fatigue Disorder><Chronic Fatigue Syndrome><Chronic Fatigue and Immune Dysfunction Syndrome><Chronic Infectious Mononucleosis-Like Syndrome><Clinical><Clinical assessments><Co-Stimulator><CoV-2><CoV2><Collecting Cell><Collection><Consent><Coronavirus Infectious Disease 2019><Costimulator><Cryofixation><Cryopreservation><DNA><Data><Data Collection><Deoxyribonucleic Acid><Development><Diagnosis><Diagnostic tests><Disease><Disease remission><Disorder><Endocrine><Enrollment><Epidemiologic Research><Epidemiologic Studies><Epidemiological Studies><Epidemiology Research><Epidermal Thymocyte Activating Factor><Etiology><Event><Evidence based treatment><Exclusion Criteria><Exertion><Family member><Fatigue><Flow Cytofluorometries><Flow Cytofluorometry><Flow Cytometry><Flow Microfluorimetry><Flow Microfluorometry><Frequencies><Funding><Fungus Diseases><Gene Expression Monitoring><Gene Expression Pattern Analysis><Gene Expression Profiling><Goals><HHV-6B><Herpesviridae><Herpesviruses><Human><Human Herpesvirus 6B><IFN-Gamma><IFN-g><IFN-γ><IFNG><IFNγ><IL-2><IL2 Protein><Immune><Immune Interferon><Immune Surveillance><Immune response><Immunes><Immunity><Immunochemical Immunologic><Immunologic><Immunologic Surveillance><Immunologic Surveillances><Immunological><Immunological Surveillance><Immunological Surveillances><Immunological response><Immunologically><Immunologics><Immunosuppression><Immunosuppression Effect><Immunosuppressive Effect><Immunosurveillance><Individual><Infection><Interferon Gamma><Interferon Type II><Interleukin 2><Interleukin 2 Precursor><Interleukin II><Interleukin-2><Interleukine 2><Interleukine 2 Precursor><Interleukine II><Intervention><Intervention Strategies><Knowledge><Laboratories><Lack of Energy><Life><Long COVID><Long COVID-19><Long coronavirus disease><Long coronavirus disease 2019><Lymphocyte Mitogenic Factor><ME/CFS><MS patient><Macrophage><Macrophage-Derived TNF><Marrow monocyte><Measures><Mitogenic Factor><Modern Man><Monocyte-Derived TNF><Myalgic Encephalomyelitis><Mycoses><Mφ><NIH><National Institutes of Health><Nature><Non-Polyadenylated RNA><Outcome><PASC><PBMC><Participant><Pathogenesis><Patient Recruitments><Peripheral Blood Mononuclear Cell><Persons><Phenotype><Pilot Projects><Post Acute Sequelae of COVID19><Post Acute Sequelae of SARS-CoV-2><Post Acute Sequelae of SARS-CoV2><Post Acute Sequelae of severe acute respiratory syndrome coronavirus 2><Post-Acute Sequelae of SARS-CoV-2 Infection><Postviral Fatigue Syndrome><Predisposition><Prognostic Marker><Proteins><Protocol><Protocols documentation><R-Series Research Projects><R01 Mechanism><R01 Program><RNA><RNA Gene Products><Recontacts><Recurrence><Recurrent><Relapse><Remission><Research Grants><Research Project Grants><Research Projects><Ribonucleic Acid><Role><Royal Free Disease><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV2><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Saliva><Salivary><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome related corona virus 2><Severities><Severity of illness><Stress><Subcellular Process><Susceptibility><Symptoms><Syndrome><System><T cell growth factor><T cell response><T-Cell Growth Factor><T-Cell Stimulating Factor><T-Cells><T-Lymphocyte><T8 Cells><T8 Lymphocytes><TNF><TNF A><TNF Alpha><TNF gene><TNF-α><TNFA><TNFα><Testing><Thymocyte Stimulating Factor><Time><Transcript Expression Analyses><Transcript Expression Analysis><Tumor Necrosis Factor><Tumor Necrosis Factor-alpha><United States National Institutes of Health><Viral><Viral Diseases><Viral Gene Products><Viral Gene Proteins><Viral Markers><Viral Proteins><Virus><Virus Diseases><Work><Wuhan coronavirus><accessory cell><active followup><adulthood><adverse sequelae of COVID><adverse sequelae of COVID-19><adverse sequelae of coronavirus disease><adverse sequelae of coronavirus disease 2019><after COVID-19 infection><after SARS-CoV-2 infection><after SARS-CoV2 infection><after infection by SARS-CoV-2><after severe acute respiratory distress syndrome CoV-2 infection><analyze gene expression><analyzing longitudinal><antigen-specific T cells><bacteria infection><bacterial disease><biobank><biologic><biorepository><causation><chronic COVID><chronic COVID-19><chronic COVID-19 sequelae><chronic novel coronavirus disease 2019><clinical phenotype><cohort><cold preservation><cold storage><comparator group><comparison group><coronavirus disease 2019><coronavirus disease 2019 virus><coronavirus disease-19><coronavirus disease-19 virus><coronavirus infectious disease-19><design><designing><develop a vaccine><develop vaccines><development of a vaccine><developmental><diagnostic criteria><digital><disease causation><disease severity><enroll><epidemiologic investigation><epidemiology study><flow cytophotometry><follow up><follow-up><followed up><following COVID-19 infection><following SARS-CoV-2 infection><following SARS-CoV2 infection><following infection by SARS-CoV-2><following severe acute respiratory distress syndrome CoV-2 infection><followup><fungal infection><fungus infection><gene expression analysis><gene expression assay><hCoV19><herpes virus><host response><immune suppression><immune suppressive activity><immune suppressive function><immune system response><immunoresponse><immunosuppressive activity><immunosuppressive function><immunosuppressive response><inclusion criteria><interventional strategy><lFN-Gamma><latent infection><long haul COVID><long haul COVID-19><long haul coronavirus disease><long haul coronavirus disease 2019><long haul sequelae of COVID-19><long haul sequelae of coronavirus disease 2019><long-hauler COVID><long-hauler COVID-19><long-hauler coronavirus disease 2019><long-hauler syndrome><long-term COVID><long-term COVID-19><long-term coronavirus disease><long-term coronavirus disease 2019><long-term sequelae of COVID-19><long-term sequelae of SARS-CoV-2><long-term sequelae of coronavirus disease 2019><long-term sequelae of severe acute respiratory syndrome coronavirus 2><longitudinal analysis><longterm COVID><longterm COVID-19><longterm coronavirus disease><longterm coronavirus disease 2019><monocyte><multiple sclerosis patient><nCoV2><neural><participant recruitment><patients with MS><patients with multiple sclerosis><people with Multiple sclerosis><persistent COVID-19><pilot study><post COVID syndrome><post COVID-19 sequelae><post COVID-19 syndrome><post SARS-CoV-2 infection><post acute COVID syndrome><post acute COVID-19><post acute COVID-19 syndrome><post acute SARS-CoV-2><post acute coronavirus disease 2019><post acute coronavirus disease 2019 syndrome><post acute coronavirus disease syndrome><post acute sequelae following COVID-19><post acute severe acute respiratory syndrome coronavirus 2><post coronavirus disease 2019 syndrome><post coronavirus disease syndrome><post-acute phases of COVID-19><post-acute sequelae following SARS-CoV-2 infection><post-acute sequelae of COVID-19><post-acute sequelae of acute COVID infection><post-acute sequelae of coronavirus disease 2019><previous COVID-19 infection><previous SARS-CoV-2 infection><previous SARS-CoV2 infection><previous severe acute respiratory distress syndrome CoV-2 infection><prior COVID-19 infection><prior SARS-CoV-2 infection><prior SARS-CoV2 infection><prior severe acute respiratory distress syndrome CoV-2 infection><prognostic biomarker><prolonged COVID-19 symptoms><recruit><saliva sample><salivary sample><sample collection><social role><specimen collection><stem><stressor><study population><thymus derived lymphocyte><transcriptional profiling><vaccine development><vaccine for immunotherapy><vaccine immunotherapy><vaccine-based immunotherapy><viral DNA><viral RNA><viral infection><virus DNA><virus RNA><virus infection><virus protein><virus-induced disease>