Human Herpesvirus 6A Is a Risk Factor for Multiple Sclerosis

Lundström, Wangko; Gustafsson, Rasmus

doi:10.3389/fimmu.2022.840753

Cited by 13 publications

(11 citation statements)

References 87 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pre‐existing CNS pathology, especially those affecting the metabolism and integrity of neurons and glia, may make individuals more vulnerable to the consequences of coronavirus invasion and, therefore, may adversely influence COVID‐19 outcomes. Multiple sclerosis (MS) is an acquired inflammatory demyelinating disease, possibly triggered by viral infections or reactivation episodes through stimulating immune responses 17,18 . Experimental studies show that coronaviruses may cause demyelination in animal models 19 and, at least in some cases, provoke a relapse of MS in humans 20 …”

Section: Introductionmentioning

confidence: 99%

Shared genetics and causal associations between COVID‐19 and multiple sclerosis

Baranova

Cao

Teng

et al. 2022

Journal of Medical Virology

View full text Add to dashboard Cite

Neuroinflammation caused by COVID‐19 negatively impacts brain metabolism and function, while pre‐existing brain pathology may contribute to individuals' vulnerability to the adverse consequences of COVID‐19. We used summary statistics from genome‐wide association studies (GWAS) to perform Mendelian randomization (MR) analyses, thus assessing potential associations between multiple sclerosis (MS) and two COVID‐19 outcomes (severe acute respiratory syndrome coronavirus 2 [SARS‐CoV‐2] infection and COVID‐19 hospitalization). Genome‐wide risk genes were compared between the GWAS datasets on hospitalized COVID‐19 and MS. Literature‐based analysis was conducted to construct molecular pathways connecting MS and COVID‐19. We found that genetic liability to MS confers a causal effect on hospitalized COVID‐19 (odd ratio [OR]: 1.09, 95% confidence interval: 1.03−1.16) but not on SARS‐CoV‐2 infection (1.03, 1.00−1.05). Genetic liability to hospitalized COVID‐19 confers a causal effect on MS (1.15, 1.02−1.30). Hospitalized COVID‐19 and MS share five risk genes within two loci, including TNFAIP8, HSD17B4, CDC37, PDE4A, and KEAP1. Pathway analysis identified a panel of immunity‐related genes that may mediate the links between MS and COVID‐19. Our study suggests that MS was associated with a 9% increased risk for COVID‐19 hospitalization, while hospitalized COVID‐19 was associated with a 15% increased risk for MS. Immunity‐related pathways may underlie the link between MS on COVID‐19.

show abstract

Section: Introductionmentioning

confidence: 99%

Shared genetics and causal associations between COVID‐19 and multiple sclerosis

Baranova

Cao

Teng

et al. 2022

Journal of Medical Virology

View full text Add to dashboard Cite

show abstract

“…Several hypotheses for HHV-6A in the pathogenesis of multiple sclerosis have been suggested. 5 , 38 , 39 A direct injury from lytic HHV-6A infection in oligodendrocytes could cause cell death, demyelination and subsequent inflammation. Similar processes have been observed for JC Polyomavirus in progressive multifocal leukoencephalopathy and measles virus in subacute sclerosing panencephalitis.…”

Section: Discussionmentioning

confidence: 99%

“…One such candidate is human herpesvirus 6 (HHV-6), which has been repeatedly associated with multiple sclerosis risk. 5 While many previous studies did not distinguish between the two different species HHV-6A and -6B (collectively referred to as HHV-6), several studies now indicate that the association with multiple sclerosis is attributable to HHV-6A. 6-9 As a neurotrophic virus, HHV-6A can infect oligodendrocytes.…”

Section: Introductionmentioning

confidence: 99%

Human herpesvirus 6A and axonal injury before the clinical onset of multiple sclerosis

Grut,

Biström,

Salzer

et al. 2023

Brain

Self Cite

View full text Add to dashboard Cite

Recent research indicates that multiple sclerosis is preceded by a prodromal phase with elevated levels of serum neurofilament light chain (sNfL), a marker of axonal injury. The effect of environmental risk factors on the extent of axonal injury during this prodrome is unknown. Human herpesvirus 6A (HHV-6A) is associated with an increased risk of developing multiple sclerosis. The objective of this study was to determine if HHV-6A serostatus is associated with the level of sNfL in the multiple sclerosis prodrome, which would support a causative role of HHV-6A. A nested case-control study was performed by crosslinking multiple sclerosis registries with Swedish biobanks. Individuals with biobank samples collected before the clinical onset of multiple sclerosis were included as cases. Controls without multiple sclerosis were randomly selected, matched for biobank, sex, sampling date and age. Serostatus of HHV-6A and Epstein-Barr virus was analysed with a bead-based multiplex assay. The concentration of sNfL was analysed with single molecule array technology. The association between HHV-6A serology and sNfL was assessed by stratified t-tests and linear regressions, adjusted for Epstein-Barr virus serostatus and sampling age. Within-pair ratios of HHV-6A seroreactivity and sNfL were calculated for each case and its matched control. To assess the temporal relationship between HHV-6A antibodies and sNfL, these ratios were plotted against the time to the clinical onset of multiple sclerosis and compared using locally estimated scatterplot smoothing regressions with 95% confidence intervals (CI). Samples from 519 matched case-control pairs were included. In cases, seropositivity of HHV-6A was significantly associated with the level of sNfL (+11%, 95% CI 0.2–24%, P = 0.045) and most pronounced in the younger half of the cases (+24%, 95% CI 6–45%, P = 0.007). No such associations were observed among the controls. Increasing seroreactivity against HHV-6A was detectable before the rise of sNfL (significant within-pair ratios from 13.6 years versus 6.6 years before the clinical onset of multiple sclerosis). In this study, we describe the association between HHV-6A antibodies and the degree of axonal injury in the multiple sclerosis prodrome. The findings indicate that elevated HHV-6A antibodies both precede and are associated with a higher degree of axonal injury, supporting the hypothesis that HHV-6A infection may contribute to multiple sclerosis development in a proportion of cases.

show abstract

“…The effect of patients with post-COVID-19 syndrome on central nervous system diseases may affect the progression of neurological diseases by affecting the metabolism of neurons or glial cells [ 6 , 7 ]. The nervous system is the most complex part of the body, and when the disease of the nervous system encounters COVID-19, the diagnosis, treatment and prognosis of patients will face a severe test.…”

Section: Introductionmentioning

confidence: 99%

Causal associations of COVID‐19 on neurosurgical diseases risk: a Mendelian randomization study

Dai,

Lyu,

Zhou

et al. 2024

Hum Genomics

View full text Add to dashboard Cite

Many researchers have explored the potential association between one neurosurgical disease and coronavirus disease 2019 (COVID-19), but few systematically analyzed the association and causality between COVID-19 and various neurosurgical diseases. A Mendelian randomization analysis was conducted to evaluate the causal association between COVID-19 (including critically ill COVID‐19, hospitalized COVID‐19, and respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection) and 30 neurosurgical diseases within European populations. The consequences of inverse variance weighted models suggest that genetic susceptibility of critically ill COVID-19 may increase the risk of cerebral infarction (odds ratio [OR] = 1.02; p‐value = 0.006), genetic susceptibility of SARS-CoV-2 infection may increase the risk of stroke (OR = 1.02; p‐value = 0.047), and conversely, genetic susceptibility of hospitalized COVID-19 may reduce the risk of pituitary adenoma and craniopharyngioma (OR = 0.90; p‐value = 0.032). In addition, evidences revealed potential associations between genetic susceptibility of COVID-19 and spinal stenosis (OR = 1.03; p‐value = 0.028), diffuse brain injury (OR = 1.21; p‐value = 0.040) and focal brain injury (OR = 1.12; p‐value = 0.040). By testing for heterogeneity and pleiotropy, the above causal conclusions are robust. In summary, our analysis shows that COVID-19 has an independent and powerful causal influence on multiple neurosurgical disorders.

show abstract

Human Herpesvirus 6A Is a Risk Factor for Multiple Sclerosis

Cited by 13 publications

References 87 publications

Shared genetics and causal associations between COVID‐19 and multiple sclerosis

Shared genetics and causal associations between COVID‐19 and multiple sclerosis

Human herpesvirus 6A and axonal injury before the clinical onset of multiple sclerosis

Causal associations of COVID‐19 on neurosurgical diseases risk: a Mendelian randomization study

Contact Info

Product

Resources

About