MS Brain Lesions Linked to Early-life Viral Infection in Mice, Way of Blocking Inflammatory Spread Seen

MS Brain Lesions Linked to Early-life Viral Infection in Mice, Way of Blocking Inflammatory Spread Seen

An experimental treatment known as OB-002, that works to block an inflammatory molecule in the brain, prevented the development of lesions there after an early-in-life viral infection in a mouse model of multiple sclerosis (MS).

The research “Brain-resident memory T cells generated early in life predispose to autoimmune disease in mice,” was published in the journal Science Translation Medicine.

The association between viral infections in childhood and the risk of later developing autoimmune disorders such as MS is supported by epidemiological studies — studies of diseases in populations of people or animals. Still, the biological mechanism or process linking the two remains unknown.

A research team from Switzerland and Germany found that viral infection in the brains of mice early in life, but not at a later age, worsened those MS symptoms evident in a brain, like lesions, at sites where the virus had resided but was cleared. These changes were induced by immune T-cells containing the CD4 cell surface marker and specific for myelin, the protective layer of nerve fibers that is destroyed in MS.

Sites of infection showed a chronic inflammatory profile with brain-resident memory T-cells — which protect against recurrent or reactivated infection — containing CCL5 (also known as RANTES). This pro-inflammatory molecule has been suggested to be involved in myelin formation and cellular metabolism.

“Early-life infection of mouse brains imprinted a chronic inflammatory signature that consisted of brain-resident memory T-cells expressing the chemokine (C-C motif) ligand 5 (CCL5),” the researchers wrote.

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Researchers then found that blocking CCL5 signaling using OB-002, Orion Biotechnology Canada’s CCR5 receptor blocker, prevented the formation of brain lesions in the MS mouse model.

Of note, in mouse and human brains, T-cells containing CCL5 are mainly located at sites with activated microglia — innate immune cells in the central nervous system associated with the development of MS lesions and with myelin loss.

Overall, the results showed that “transient brain viral infection early in life worsened lesion development and symptoms in a mouse model of autoimmune disease,” and that “autoimmune lesions were spatially associated with areas of previous viral infection in mice,” the researchers wrote.

“Mechanistically, early-life viral infection induced a persistent population of CCL5–expressing brain-resident memory T-cells that promoted a long-lasting proinflammatory environment. Blockade of CCL5 signaling prevented the increased predisposition to autoimmunity in the mouse model,” the team added.

“It is very exciting to have identified a possible pathway linking virus infection early in life to MS pathology, and intriguing that it should be dependent on the activation of a single chemokine receptor,” Doron Merkler, the study’s senior author and a professor at University of Geneva and University Hospitals of Geneva, said in a press release.

Oliver Hartley, a study co-author and Orion’s vice-president for drug discovery, added: “We are thrilled to see that OB-002 shows such high efficacy in this preclinical context. These data provide a clear rationale to move forward with the development of OB-002 as [a] novel agent for the treatment of MS.”

José is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has studied Biochemistry also at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario, in London, Ontario. His work ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.
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José is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has studied Biochemistry also at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario, in London, Ontario. His work ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimer’s disease.
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46 comments

  1. Rhonda says:

    Jen, I had Measles, German Measles, Chicken Pox, and Whooping Cough before age 4. I am 61, so there were no vaccines.
    I also wondered if the early exposures were part of my MS puzzle.
    Very intetesting article.

    • Aubri J Shauger Haley says:

      My parents held devoted Christian Scientist beliefs until I was in the 3rd grade. Needless to say, I had a horrible case of the chicken pox and I didn’t get any vaccines until I was in 3rd grade. I remember in 8th grade being pulled out because of a measles outbreak and the nurse saw a page in my file showing “religious exemption” so she pulled me from class only to find out all that had been changed and updated.
      I have struggled most of my life with hard to diagnose issues and when I lost my vision, lucky I already had a neurologist. The MRI told a clear MS story that left little for interpretation. Four lessions. It was baffling to my Dr how I had actually gone so long with no other real signs prior to that. It has truly baffled us all. So we continue our cross roads. Hopefully answers will come. Thank you for guidance and support.

  2. Noai says:

    A classmate and myself in college both came down with H1N1 flu and then soon after developed autoimmune responses, mine turned out to be MS. Could there be a link there?

    • Eileen says:

      I also had a very bad case of the flu which I think was the trigger, combined with mono – Epstein Barr as a teenager.

    • Christina says:

      I think you had MS & the flu caused trauma & triggered a relapse. I do not believe you got MS from the flu. I got a hysterectomy & that triggered a severe relapse that led to my diagnosis. After seeing many specialists & doing much research & looking at my MRI’s I had MS since early years & did not realize I had it. My symptoms were drugged off for other things. I was hospitalized at a young age with the chicken pox 2x, had mono (EBV) & hospitalized with Scarlet Fever all before I was 8yrs of age. Before my diagnosis in my early 20’s I suffered with shingles & neuropathy & pain. The ONLY time I felt the best I’ve ever felt in my life, was when I was pregnant. Why because when you’re pregnant MS goes into remission I had plenty of energy I was never tired I felt like a new person it was amazing I loved being pregnant and all along I had no idea I was suffering with multiple sclerosis. At the age of 41 I got another bad case of vertigo and for years I haven’t been able to see everything was blurry and I always just chalked it up to old age never got glasses never seen an eye doctor just adjusted and when I went to the doctor because I was constantly so tired they gave me pills for depression until one day my legs went completely numb and then they did an MRI and discovered that I had MS and I had had it for over 20 years they figure.

      • Jennifer says:

        That is so interesting and have never connected being pregnant with Ms. I also felt my very very best pregnant each time and also loved it like you because of the reasons you stated.

  3. Jean says:

    The last fever I had was when I had measles when I was twelve. I have also wondered about a connection with that and my MS in diagnosis in adulthood.

  4. Michelle lalonde says:

    I also have ms I’m 60 was diagnosed 30 yrs ago only took docs 10yrs to figure it out?anyway I also beleive that it could be viral infections at my young age I had many lots of strep throat and bad case of measles and lots of cold sores was always sick and no one had any idea about ms back them I still suffer from unknown infections plus strep urinary cold sores bad ones rashes unknowen and there was a huge study done on traumatic events maybe being a part of ms in young people I had that to omg so many in knowens wish scientists could connect the dots all the best to all the poor people suffering with this painful depressing life stopped way to short 😂

    • Mary says:

      I was diagnosed 16 years ago at the age of 30. As a child I had a bad case of chicken pox although I was vaccinated. I had many cases of cold/canker sores and UTIs/kidney infections, and severe mono my first year of high school. I am also JC positive.

        • Cynthia King says:

          Tysabri worked the best for me. It’s a real commitment with all the MRIs and monthly visits. PML (a very nasty side affect). I also have the JC virus. The three things that increased the risk for PML 1) being on the drug longer than 24 months, 2) having an organ transplant 3) having the JC virus. Had to to stop because I had two out of the three. 1&3

    • Pam Ripperger says:

      Michelle I’ve also had strep throat as a teenager til 17! Also flu as an infant in Chicago flu Epidemic in 1958! I’ve always believed what the scientists are now saying! I’m 61 yrs old, diagnosed in 1993. I’ve had mild case of MS, very lucky. Can’t walk 4 first time because of Air conditioner going out in 120 degree weather in desert where I live in Arizona in the United States. That happened 21/2 yrs ago still not walking! Otherwise healthy. I was told by pain foundation staff to take Vitamin D3 5000 iu’s a day. I have not been sick & no flu 4 over a year! Try it, gel caps everywhere & inexpensive to buy! Let me no if works 4 you! Pam Ripperger from Scottsdale AZ

      • Camilla says:

        I take vitamin D3 50000 once a week. Right now I fatigue with cognitive issues. I’m on ocrevus and not die until next week for my 3rd infusion. Other than that I’m good.

  5. Michelle lalonde says:

    I would like to connect with a female or male who has suffered with ms symptoms just to talk about different possible siulotions to my unexplained symptoms for the last 30 yrs one hard to deal with question that is so frustrating is how friends family have the opinion that I look well so there fore I am well I’m not well and it’s so hard hiding my real health problems? Please any one who would like to chat please do I’m a 60yr old femal divided still walking most day but live alone family lives in Calgary and have so many unanswered question thanks Michelle lalonde

  6. Tracy Hoff says:

    My body was never the same after getting the shingles. Six years later, I was diagnosed with MS. I wasn’t young though when I got the shingles, I was 37

  7. PAMELA MALDONADO says:

    Wow I’ve always wondered about illness I had as a child and tried my hardest to make a connection. The last time I was sick (before my MS) I had a massive migraine with some coughing. I never got sick much besides a cold here or there with coughing! I always had some sort of cough if I was sick…

  8. Shannon says:

    I had a severe case of mononucleosis when I was 18. I never regained my stamina and my immune system tanked. I was diagnosed with MS when I was in my late 40’s. I believe the myriad of health issues I have experienced over the years are all connected.

    • DEC says:

      I had mononucleosis at age 17. It was the sickest I’ve ever been in 59 years. I first experienced MS symptoms at 25. ( dizziness, vertigo, numbness, etc) For ~ 6 months I had symptoms that were diagnosed as neuropathy or just a pinched nerve. (I knew it wasn’t a pinched nerve. MS was never mentioned.) I then had a 25 year respite. The above systems came back periodically at age 50. It took 2 years to get a MS diagnosis at age 52. My neurologist really thought it wasn’t MS and did a lumbar release and MRI to rule out MS. Both procedures overwhelmingly indicated MS. I’ve had the diagnosis and medication for 7 years. In the scheme of things, my neurologist and I think I’m doing well. Fatigue, memory issues, and some dizziness are on and off issues, but I go to work every day and function fairly well. I’m very thankful! ( I have RRMS.)

  9. Was there a specific “viral infection” or is it just any “viral infection” because 100% of children get a viral infection, if not multiple viral infections in their early years.
    This basically proved nothing.

    • Angie says:

      Zachari, I was thinking the same thing. What 40/50/60/70 year old hasn’t had the flu, chicken pox, etc. It would be helpful if the article indicated which “viral infections” caused the MS like symptoms.

  10. Gail says:

    The article left many questions, as it didn’t point our which viral infection they’re talking about, however, note that it said an infection “early in life.” It may be that those who are especially susceptible to viruses may have had one as children that they’re not even aware of.

  11. America Quinn says:

    I got my first flu shot when I was 39. I developed tingling and numbness and weakness in my legs. I ended up in the hospital 5 days getting steroid treatment They called it transverse myelitis. Next year I took another one the exact same thing happened I finally got diagnosed with MS. I haven’t taken another one since but it is too late.I believe it was that flu vaccination!

    • Camilla says:

      I was diagnosed with transverse myelitis in 2003 then MS in 2016. Prior to 2003 I had an unknown illness that caused me to lose a lot of weight. 165 lbs down to 118 lbs in 3 months. Since I couldn’t keep anything down not even ice chips. I was on an iv for a few months. Drs thought it was my gall bladder and took it out but I had no improvement
      Then one day I could drink water without vomiting.
      I had the diagnosis of TM in 2003, i got shingles in 2012 then MS in 2016.

    • Melissa says:

      How long after your flu shot? I prob had one or 2 flu shots in my lifetime. I had strep with alot when I was young and had it with alot of complications when I was an adult. Had been over 10 years and stupidly got another flu shot. 5 weeks later in hospital numb up to my waist and diagnosed with a rare type of ms Balos Concentric Sclerosis at 43 years old. 3 years later I am living a good life. I am taking Aubagio. Praying for a cure as I do get tired and my knees hurt…but really cannot complain at all.

    • Annie says:

      Same here I got whooping cough and flu shot two days later I started a very long path of sickness and ten years later I’ve got numbness nerve burn vertigo the worst case of brain fog memory loss trigeminal neuralgia so many other symptoms and finding a neurologist in my area has been a nightmare I am praying that Dr. Lulu in Carmichael California will take care of me And get me on the right track. I have a question do any of you have MTHFR Gene they have linked MS to it and I have double mutation from mother and father it is the inability to process folic acid which is put in to most of our foods my body turns it into cyanide which then attacks my nerve endings and leaves them exposed Causing MS

    • Christy K says:

      I am 49 years old, diagnosed with MS in 1994 at the age of 24. I have secondary progressive now which happened slowly over the last 6-8 years. I too had reoccurring strep throat as a teenager and mono at 17 years of age. I have always believed that this set my system up for developing an autoimmune disease. The icing on the cake was getting struck by lightening (ground strike which traveled to a tent pole I was hanging on to) at age 23. I was diagnosed with MS about 8 months later when I had numbness and tingling in my left hand/arm. The same arm/hand that was hanging on to the tent pole. Not a coincidence I am sure.

    • Judy says:

      Hi, I got first and only flue shot way back in my thirties, I was paralyzed from the waist down, I’m in my 60 now and have so many auto anyone diseases to count. I was sick alot when I was a child, very poor. So my parents didn’t take me to Dr much. Lots of infections. I’m on lots of medications, I have so many diseases that I’m sure that Ms is in there. All the symptoms are the same as other autoamune diseases, I hate it, my life is just day to day.

  12. Toni says:

    Impetigo and reoccurring tonsillitis before age 10. Severe mononucleosis at age 20. Plus, at least 3 concussions by that time. And I was living in a smoke filled house and started smoking myself at 15. Quit for 10 years and started again in my 40’s and diagnosed with MS at 47.

  13. Janet Orchard says:

    As a child I had measles, German measles, Scarlet Fever and Scarletina all more than once, whooping cough, and Chicken Pox so bad they thought I wouldn’t pull through. IBS in 20’s, PPMS in 40’s, wheelchair user for the last 20 years. I have been following the Ann Boroch Candida Protocol for 5 years and other than a balance problem have no other symptoms of MS now. Happy to chat to anyone I can help by sharing my experiences.

    • Kathleen says:

      For us that have ms There are 50+ genes in our body related to ms Different viral, bacterial infections, vaccinations or trauma to the body, a toxic overload of heavy metals put stress on our brain and bodies and the ms gene is activated and outcomes MS and all the different symptoms along with it. Just my thought. Had ms since 2000, cancer in 2004, Fibromyalgia in 2008, Lupus in 2010. Been on 7 different ms drugs, maybe they brought on all the other autoimmune diseases.

  14. Robin Schoonover says:

    Hi everyone! This article was very interesting to me. I am 41 and was diagnosed with MS when I was 29. I also had strep throat a lot growing up. I have also had bad trauma to the head about 4 times. I thought it was interesting how they mentioned viral infections and mice. About 3 years prior to being diagnosed with MS I was working at a job that was badly infested with mice. They were always on the counters and crawling all over everything. This is something that I have always wondered about is if maybe I picked up something viral from these mice. I wonder if there’s a link??

  15. Shelia Gaiser says:

    I also had impetigo as a very young child and many later chronic cases of tonsilitis. Reading this article actually caused me to pause and remember the impetigo and posdible link. All this caused me to google what type of bacteria was involved and the other related illnesses. I found an article that is very interesting and if yoh read far enough into it (page 3or4, it begins to mention the effects on T-cells.
    https://www.google.com/url?sa=t&source=web&rct=j&url=http://textbookofbacteriology.net/staph_2.html&ved=0ahUKEwj9w-Xf9ebjAhVDR60KHXORCf8QFgiJATAN&usg=AOvVaw2GGHb8GrVmFQmJXhSqNOaD

  16. Jane says:

    I have not been diagnosed with MS but have the lesions found on an MRI. Had mono at
    15 and shingle at 42
    but they say that I have
    Fibromyalgia . Can’t seem to get any more answers ☹️

  17. Christine says:

    I have had some unknown virus many times since I was about 7 or 8. On top of having had strep throat more than anyone ever should have to, I had tonsils out. I then began having episodes of what they just called Viral Pharyngitis. Very painful ulcers all over throat and ear tubes. Lasts about a week or two then gone. Just had it again for the first time in years.
    And for the first time I years I have new lesions on my MRI..🤔

  18. Christine says:

    I have had some unknown virus many times since I was about 7 or 8. On top of having had strep throat more than anyone ever should have to, I had tonsils out. I then began having episodes of what they just called Viral Pharyngitis. Very painful ulcers all over throat and ear tubes. Lasts about a week or two then gone. Just had it again for the first time in years.
    And for the first time I years I have new lesions on my MRI..🤔 PPMS

  19. Karri Thompson says:

    I had many strep throats as a very young child, but I’m almost certain I know what turned on the MS genes (runs in my family): At age 13 1/2, 1984, I developed Haemophilus Influenza b, or Hib. It’s now a vaccine babies receive.
    It’s one of many illnesses that cause meningitis (I didn’t), but I was very sick with a fever of 105*. I went on to develop CIS 12 years later, then MS diagnosis in 2001.

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