Herpes Virus 6A Infection Increases Multiple Sclerosis Risk

by | Dec 16, 2019 | 2019, Brain Health, Multiple Sclerosis

Written by Joyce Smith, BS. Study demonstrates that an increased serological response against human herpesvirus 6A is associated with risk for multiple sclerosis.

blood diseases microscopeMultiple Sclerosis (MS) is a typically progressive disease characterized by central nervous system inflammation involving demyelination of the sheaths of nerve cells in the brain and spinal cord, and with several different disease courses: relapsing remitting MS (RRMS), secondary progressive MS (SPMS), and primary progressive MS (PPMS). While a genetic predisposition does exist 1, lifestyle/environmental factors, like virus infections and smoking also play a role, often interacting with MS risk genes 2. The gamma herpes virus, Epstein-Barr virus (EBV), remains highly suspect in the MS etiology 3; however, the beta-herpes virus, cytomegalovirus (CMV), has no association with MS risk 4.

Eighty percent of children are infected with the HHV-6 virus before the age of two. This primary HHV-6B infection results in roseola, a disease characterized by high fever, rashes, and occasional febrile seizures 5. As with all herpes viruses, HHV-6A and HHV-6B can become latent in the body, and can potentially emerge later in life to develop into serious disease such as encephalitis. HHV-6A has repeatedly been reported to be associated with MS 6. However, controversy exists because studies have been limited in size or unable to separate the HHV-6A from HHV-6B serologically, thus increasing the need to quantify their respective roles in MS.

In the current study 7, the research team developed a comprehensive population-based case-control study using serological methods that can distinguish between the HHV-6A from HHV-6B viruses. They compared antibody levels in blood samples of a cohort of 8,700 of patients with MS against more than 7,200 healthy individuals (controls) whose gender, date of birth, date of blood sample and other factors matched those with MS. Using a novel multiplex serological assay, the team measured IgG reactivity in the blood against the immediate early protein1 from HHV-6A (IE1A) and HHV-6B (IE1B), which diverges the most between the two viruses.

  • They found that IgG response against IE1A was positively associated with MS (OR = 1.55, p= 9 × 10−22). In contrast, the IgG response against IE1B was negatively associated with MS (OR = 0.74, p = 6 × 10−11).
  • In a sub-group of almost 500 people whose blood samples were drawn before disease onset, the risk of developing MS in the future was more than doubled if they had an HHV-6A viral infection (OR = 2.22, p = 2 × 10−5).
  • People who were younger when HHV-6A was first discovered in their blood had a higher future risk of developing MS (OR=1.55, p = 9 x 10-22).
  • People with MS and a history of smoking also had higher IE1A IGA levels compared to those who never smoked (p = 2×10-5).
  • With respect to the Epstein-Barr virus (EBV), serological testing found that antibodies to EBV were also associated with MS (attributable proportion = 0.24, p = 6 × 10−6), and that individuals affected with both EBV and HHV-6A viruses had an even greater risk of MS.
  • The IgG response against HHV-6B IE1B was negatively associated with MS (OR = 0.74, p = 6 ×10−11). The association did not differ between MS subtypes or vary with MS severity.
  • Lastly, when genetic associations were mapped, researchers found that HHV-6A proteins were associated with HLA genes, suggesting a potential predisposition to MS.

Source: Engdahl, Elin, Rasmus Gustafsson, Jesse Huang, Martin Biström, Izaura Lima Bomfim, Pernilla Stridh, Mohsen Khademi et al. “Increased serological response against human herpesvirus 6A is associated with risk for multiple sclerosis.” Frontiers in Immunology 10 (2019): 2715.

© This is an Open Access article.

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Posted December 16, 2019.

Joyce Smith, BS, is a degreed laboratory technologist. She received her bachelor of arts with a major in Chemistry and a minor in Biology from  the University of Saskatchewan and her internship through the University of Saskatchewan College of Medicine and the Royal University Hospital in Saskatoon, Saskatchewan. She currently resides in Bloomingdale, IL.

References:

  1. Sawcer S, Hellenthal G, Pirinen M, et al. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature. 2011;476(7359):214.
  2. Olsson T, Barcellos LF, Alfredsson L. Interactions between genetic, lifestyle and environmental risk factors for multiple sclerosis. Nature Reviews Neurology. 2017;13(1):25.
  3. Bjørnevik K, Riise T, Bostrom I, et al. Negative interaction between smoking and EBV in the risk of multiple sclerosis: The EnvIMS study. Multiple Sclerosis Journal. 2017;23(7):1018-1024.
  4. Sundqvist E, Bergström T, Daialhosein H, et al. Cytomegalovirus seropositivity is negatively associated with multiple sclerosis. Multiple Sclerosis Journal. 2014;20(2):165-173.
  5. Hall CB, Long CE, Schnabel KC, et al. Human Herpesvirus-6 Infection in Children–A Prospective Study of Complications and Reactivation. New England Journal of Medicine. 1994;331(7):432-438.
  6. Álvarez-Lafuente R, García-Montojo M, De Las Heras V, Bartolomé M, Arroyo R. Clinical parameters and HHV-6 active replication in relapsing—remitting multiple sclerosis patients. Journal of Clinical Virology. 2006;37:S24-S26.