Prepared By
Richard Dowson, B.Ed., Ed. Dip, M.Ed., Moose Jaw, Saskatchewan, CANADA
There are Two Strains of Epstein Barr Virus, EBV-1 and EBV-2
The strains are based on the variations in their genetic code. EBV-1 readily transforms B cells, (B lymphocytes) in culture while EBV-2 does poorly at transforming.
EBV-1 is common in Europe, Asia (including China), North and South America.
Contrast: The MS prevalence rate in China in 2013 was 5.2 cases/100,000 population. The PR in Europe is 142.81/100,000 and 117.49/100,000 in the Americas. The rates of EBV and low PR of MS in China is contradictory.
Consider Zhang, G.X., et al, (2020), in their Paper, “Incidence and prevalence of multiple sclerosis in China and other Asian countries” writes, “… Asian populations presenting 80% less risk of MS…” compared to Europe and the Americas. The Paper continues, “Prevalence rates in China range between 0.88 cases/100,000 population in 1986 and 5.2 cases/100,000 population in 2013.” In “Japan, where figures ranged between 8.1 (1986) and 18.6 cases/100,000 population…” in 2013. Chinese don’t usually keep indoor pets. Japanese do.
Contrast: If EBV-1 was a culprit, MS prevalence in China would be like that in Europe.
Contrast: EBV-2 is most common in Alaska, Papua New Guinea and Central Africa. MS prevalence in the Western Pacific is 4.79 and 8.6 in Africa. These numbers do not seem to agree with the proposal. The numbers are not even similar. Almost everyone has EBV. Relatively speaking, almost no one has MS.
EBV Challenges – Continued
Chuck Dinerstein, MD, MBA, writing for the American Council on Science and Health, January 25, 2022 says, “… the difficulty of calling EBV the “causative” agent of MS is that most people with EBV do not develop MS.” He adds, “So when we speak of EBV as a cause of MS, recognize that it is necessary, but not sufficient – there is no causative smoking gun.”
Alan Rickerson, formerly of the Institute of Cancer Studies at U of Birmingham, “… only a tiny sliver of people infected with the virus end up developing multiple sclerosis, so some other trigger or triggers must also be in play…”. (Zhang – Atlantic Monthly)
Contrast: ‘An environmental factor’, in the form of a virus, is referenced by some MS researchers. Is the ‘environmental factor’ a demyelinating virus.
Indoor Pets – Farm Dogs – Canine Distemper Virus (CDV)
The most common demyelinating virus present in regions of high prevalence of MS is CDV. Indoor pet dogs and cats, and farm dogs are common in Canada, the Northern United States and Europe. Indoor pet dogs and cats, and farm dogs are not common in sub-Saharan Africa or among Inuit.
Can Zoonosis Happen?
As an environmental factor, casual interactions during adolescence with a pet or farm dog while the animal is shedding or the immune system is compromised due to illness, such as Mono, provides an opportunity for Zoonosis. Like all illnesses, several factors are at play.
A Review of the January 2022 Harvard and Stanford Research into a Connection Between Epstein Barr Virus and Multiple Sclerosis
EBV has an established connection to certain cancers.
Evidence is abundant for EBV related malignancies in Inuit and people with Endemic Burkitt Lymphoma in Sub-Saharan Africa. MS does not appear to be directly related to malignancies of epithelial tissue or tumors.
As Domenico Plantone notes in his 2015 Paper “Concurrence of Multiple Sclerosis and Brain Tumors” in Frontiers in Neurology wrote, “Multiple sclerosis (MS) is a chronic demyelinating inflammatory disease of the central nervous system…”. Plantone adds, “Although the co-existence of MS and brain tumors has been long described, many doubts regarding their possible causal association persist.”
Immune Suppressant Drugs – Effect on People with MS
Lebrun and Rocher, in their 2018 Paper, “Cancer Risk in Patients with Multiple Sclerosis: Potential Impact of Disease-Modifying Drugs”, reviewed some MS Drugs. They wrote, “Because of their action on the immune system, and due to a lack of available long-term data, a special warning of the potential risk of cancer…” is placed on drugs.
This Paper has no opinion on MS Treatment.
Is a Weakened the Immune System a Factor in Zoonosis?
‘Mono’, caused by EBV, is most common in teenagers and those in their 20s. It seems to occur in children but is asymptomatic. Being ‘most common in adolescents’ is an important consideration. This is the common age range identified by Cook and Dowling as the time Zoonosis occurs, with exposure to Canine Distemper Virus, a variant of the Measles Virus. (Uhl 2019)
Olivia Hatton et al, write, “Human B cells are the primary targets of Epstein Barr virus (EBV) infection.” This should be considered when looking at the immune system and a Zoonotic ‘transfer’ infection of a ‘measles like’ virus.
Reference: Olivia Hatton et al, “The Interplay Between Epstein Barr Virus and B Lymphocytes: Implications for Infection, Immunity, and Disease” Immunology Resources, 2014)
A strong immune system protects against Zoonosis. The question remains, does Infectious Mononucleosis weaken the immune system thus providing an opportunity for Zoonosis?
Mononucleosis and a Weakened Immune System – Considerations
Normally, the immune system ‘fights’ infections using white blood cells, B lymphocytes (B Cells) that make antibodies to fight off an ‘invader’. Human Herpes Virus 4 (HHV-4) that causes Infectious Mononucleosis (Mono) is a challenging story. As Dr. Kerkar notes, “… mononucleosis, the virus itself invades the B cells and takes control of the functions.” He continues, “This may also lead to an imbalance between the virus transformation and the immune system that leads to the development of various lymphoproliferative disorders.”
Contrast: EBV can cause ‘chaos’ in the immune system making it a risk factor for MS.
Mono weakens the immune system putting the individual in a critical position for ‘exposure’ to an environmental risk factor. As Kerkar writes, “…the mononucleosis also weakens the immune system thereby reducing the capacity for fighting against infection.” He continues, “… mononucleosis increases the incidences of autoimmune diseases such as systemic lupus erythematosus.”
Contrast: Personal interviews, People with MS one person with MS never had ‘Mono’.
Dr. Kerkar concludes, “Epstein Barr virus directly invades the B cells of the immune system and controls their function through changes in the transcription factor. Mononucleosis weakens the immune system.”
Reference: Kerkar, Pramod, M.D., FFARCSI, DA, “Does Mono Weaken the Immune System?”, General Open Article, “Does Mono Weaken Your Immune System?
Contrast: Lupus (Systemic lupus erythematosus – a systemic autoimmune disease)
John B. Harley and Judith A. James write, “Our previous work has demonstrated that years before diagnosis abnormal autoantibody responses are present in the sera of patients who will subsequently develop lupus…”. They continue, “… our results suggest that the first lupus-specific autoantibodies arise from particular antibodies directed against Epstein-Barr virus…”
John B. Harley and Judith A. James, conclude, “… an immune response against Epstein-Barr virus being important in at least some patients for the initiation of lupus autoimmunity.”
Epstein Barr Virus and Pet Dogs
Canine Distemper forms the foundation of the Cook and Dowling Hypothesis. Here is a review of EBV and pets.
In the June 2012 issue of Virology, a team from the University of Pennsylvania School of Veterinary Medicine and the Perelman School of Medicine studied EBV and dogs.
Nicola Mason, an assistant professor of medicine and pathobiology at Penn Vet wrote, “Discovering that dogs can get infected with this virus like people do may provide us with a long-sought-after model for EBV-associated disease.”
In the Shih-Hung Huang et al Paper (Virology, June 2012), they note domestic dogs and humankind share a history of at least 15,000 years.
The researchers learned, “… dogs develop spontaneous lymphoid malignancies including DLBCL (Diffuse large B-cell lymphoma) and Burkitt-like lymphoma that share remarkable similarities in biological, behavioral, genetic and cytogenetic characteristics with their counterpart subtypes in humans…”
Breed of dog plays a role. They write, “Golden Retrievers, Labradors and Miniature Schnauzers were also over-represented in the lymphoma group. Mix-breeds were over-represented in the non-lymphoma group.”
Breen and Modiano write, “These data suggest that humans and dogs share an ancestrally retained pathogenetic basis for cancer and that cytogenetic evaluation of canine tumors may provide greater insight into the biology of tumorigenesis.”
Contrast: EBV ‘like condition’ in dogs is associated with malignancies, not demyelination.
References: Breen, Matthew and Jaimie F. Modiano, “Evolutionarily conserved cytogenetic changes in hematological malignancies of dogs and humans--man and his best friend share more than companionship”, Chromosome Research 2008;16(1):145-54.
Reference: Huang, Shih-Hung, et al, “Evidence of an oncogenic Gammaherpesvirus in domestic Dogs”, Virology 2012 June 5, 427 (2), 107-117.
Zoonosis, Canine Distemper Virus and Demyelination
Canine Distemper Virus is, “a Demyelinating disease of the nervous system in which the myelin sheath of neurons is damaged. This damage impairs the conduction of signals in the affected nerves.” (Wikipedia)
CDV is a single-stranded, non-segmented, negative-sense RNA virus belonging to the genus morbillivirus, of the Paramyxovirus family that includes measles and mumps. (Wikipedia)
Lemp, Charlotte, et al (Viruses, 2014 Jul; 6(7): 2571–2601) writes it, “… is known to cause a variety of disorders in dogs including demyelinating leukoencephalitis.” It is “…characterized by lesions with a variable degree of demyelination…”.
Marc Vandevelde and Andreas Zurbriggen, in their 2005 Paper “Demyelination in canine distemper virus infection: a review”, published in Acta Neuropathology write, “Canine distemper virus (CDV) causes severe immunosuppression and neurological disease in dogs, associated with demyelination, and is a model for multiple sclerosis in man. In the early stage of the infection, demyelination is associated with viral replication in the white matter.”
Contrast: There is no reference to EBV.
Morbillivirus Paradox
Canine Distemper Virus is a variant of the Measles virus (Uhl 2019) and both are ‘Morbilliviruses’. Comparisons can be drawn between Canine Distemper Virus (CDV) and Measles Virus (MV). The Measles vaccine can prevent CDV. (Strating, A., “Measles vaccine in dogs: efficacy against aerosol challenge with virulent canine distemper virus”)
Auto-immune Paradox
Jane E. Libbey and Robert S. Fujinami, in Polymicrobial Diseases, point out that, “MV (measles virus) infection produces an immune system paradox. MV infection, while inducing lifelong immunity, also suppresses the immune system leading to an increase in susceptibility to other secondary infections.” CDV is a Variant of the Measles Virus.
Contrast: Is MS a result of an inter-play between CDV and EBV? (Measles is used here as a ‘stand-in’ for Canine Distemper Virus.)
Does Measles cause demyelination?
Yes! Ohara, (Japanese Journal of Infectious Diseases, 1999 Oct;52(5):198-200) writes, “Data regarding the immunological abnormalities to measles virus (MV) and the presence of neurological complications induced by MV infection suggest that MV may be a causative agent of the demyelination observed in MS.” (MV is a stand-in for CDV)
Although rare, Measles can cause acute disseminated encephalomyelitis (ADEM) which is a demyelinating disease.
Reference: Fazakerly, John K., and Robert Walker, “Virus demyelination”, Journal of Neuro-Virology, 9: 148–164, 2003.
Contrast: Does a Zoonotic transfer of CDV suppress the immune system resulting in an EBV eruption of Mononucleosis? Or Does Mononucleosis suppress the immune system allowing for the Zoonotic transfer of CDV? What came first? Probably Mono.
Thoughts
The Harvard and Stanford Studies present significant arguments for the emergence of MS but a broader explanation would be helpful.
The Epstein Barr virus alone does not appear to cause demyelination, the major feature of Multiple Sclerosis.
Multiple Sclerosis is the most common demyelinating disease in humans. MS is characterized by demyelination in the brain, spine, and/or optic nerve. Canine Distemper Virus causes demyelination.
Marc Vandevelde and Andreas Zurbriggen say Canine Distemper Virus “…is a model for multiple sclerosis in man…”. (Referenced)
Summary
The Alberto Ascherio team at Harvard and the Robinson and Steinman at Stanford have produced excellent, provocative studies.
As Alberto Ascherio noted, a person is 32 times more likely to develop MS if they had Mono (Epstein Barr virus). This is stunning and an very important factor.
Does EBV ‘trigger’ chaos in a hijacked immune system causing it to attack itself? OR Does Mono (EBV) weaken the immune system and open the subject to ‘infection’ by a demyelinating virus in the environmental? Where is the ‘smoking gun’?
The Robinson and Steinman, Stanford EBV Study puts their position bluntly, “Infection with Epstein-Barr virus (Mono) is the trigger for the development of multiple sclerosis.”
Contrast: Is the ‘trigger’ the Mono weakened immune system, thus providing an opportunity for the contraction of a demyelinating virus?
Viral Induced Demyelination
Stohlman and Hinton write: “…, an understanding of the diverse mechanisms used by viruses to induce demyelination may shed light into the etiology and pathogenesis of the common demyelinating disorder multiple sclerosis (MS). This notion is supported by the persistent view that a viral infection acquired during adolescence might initiate MS after a long period of quiescence. Demyelination in both humans and rodents can be initiated by infection with a diverse group of enveloped and non-enveloped RNA and DNA viruses.”
Reference: S.A. Stohlman and D.R. Hinton, (“Viral induced demyelination”, Brain Pathology)
The Harvard ad Stanford Studies are excellent. Both bring the possibility of the discovery of the cause Multiple Sclerosis closer to realization.
Test and Eliminate and Eliminate Hypothesis
There is a plethora of theories on the cause of MS. Good science says, test and eliminate.
First – test the 45-year-old Cook and Dowling Hypothesis; “Canine Distemper Virus (a Paramyxovirus and Variant of Measles or Morbillivirus) plays a major role in the etiology of MS,” adding “… zoonosis occurs, primarily, during adolescence (puberty)”. Zoonosis relates to keeping an indoor pet dog, cat or a farm dog.
Method
The technology exists. Use an “in situ-reverse transcriptase-polymerase chain reaction Test” for the presence of Canine Distemper Virus in people with MS.
No hypothesis on the Cause of MS can be considered until the 45-year-old Cook and Dowling Hypothesis is either proven or disproved.
Author’s Note: I have no affiliation with any groups or individuals. This is a pro-bono study. It was undertaken for people with MS in Alberta and Saskatchewan.
A 17-page Bibliography is available.
