Several mouse models of multiple sclerosis (MS) are now available. We have established a mouse model, in which ocular infection with a recombinant HSV-1 that expresses murine interleukin (IL)-2 constitutively (HSV-IL-2) causes central nervous system demyelination in different strains of mice. This model differs from most other models, in which it represents a mixture of viral and immune triggers. In the present study, we directly compared MOG35-55, MBP35-47 and PLP190-209 models of experimental autoimmune encephalitis with our HSV-IL-2-induced MS model. Mice with HSV-IL-2- and myelin oligodendrocyte glycoprotein (MOG)-induced demyelinating diseases demonstrated a similar pattern and distribution of demyelination in their brain, spinal cord (SC) and optic nerves (ONs). In contrast, no demyelination was detected in the ONs of myelin basic protein (MBP)- and proteolipid protein (PLP)-injected mice. Interferon-β (IFN-β) injections significantly reduced demyelination in brains of all groups, in the SCs of the MOG and MBP groups, and completely blocked it in the SCs of the PLP and HSV-IL-2 groups as well as in ONs of MOG and HSV-IL-2 groups. In contrast to IFN-β treatment, IL-12p70 protected the HSV-IL-2 group from demyelination, whereas IL-4 was not effective at all in preventing demyelination. MOG-injected mice showed clinical signs of paralysis and disease-related mortality, whereas mice in the other treatment groups did not. Collectively, the results indicate that the HSV-IL-2 model and the MOG model complement each other and, together, provide unique insights into the heterogeneity of human MS.Gene Therapy advance online publication.
In MS there is supportive evidence that a virus may be part of the problem, so in an attempt to integrate a viral and immune problem in models, in this study the researchers show that infection of the eye with the cold sore (Herpes simplex) virus that was genetically-engineered to produce a T cell growth factor called interleukin-2 causes a brain infection and causes inflammation and demyelination.
They then took the MS drug beta interferon, at least the mouse version of the human cytokine and showed that it stopped demyelination from occurring and this worked better than in the autoimmune EAE models.
This perhaps could be expected as beta interferon is an anti-viral agent it stops viruses from replicating (so is anti viral) and can stop some cells proliferating too (so it can be immunosuppressive).
This adds to the armoury of tools available to researchers and could complement studies.
Is this model MS?, well clearly not and some would argue about the internal validity of the model, because there is no good evidence that MS is caused by the cold sore virus.
Will this new model catch on? Maybe, but probably not because of potential safety issues as using a human infective virus. This means extra levels of containment to: protect the environment, other animals in the facility and not least the researchers who do the studies.
Demyelination has been seen with other neutrotrophic infections with mouse hepatitis virus, Theilers murine encephalomyelitis virus and Semliki forest virus, some have been adapted only to infect mice so are much safer. Most animal houses spend their time trying to ensure that their facilities are pathogen free and so people do not like to bring in virus as it can be a very laborious and costly exercise to get rid of it if it contaminates other stock.