Grant: Creation of a humanized CD46 mouse model for HHV-6 infection

PI: Claude P. Genain, MD, California Pacific Medical Center Research Institute, San Francisco USA

While studies have suggested that viruses may trigger Multiple Sclerosis or influence its course, a direct link to MS pathogenesis has not been discovered. Dr. Claude Genain of California Pacific Medical Center is creating a model of inflammatory demyelination through infecting mice that carry a transgene encoding for CD46, the human cellular receptor for HHV-6 and measle virus. This study is based on the success of Dr. Genain’s model of HHV-6 induced CNS demyelination in common marmosets.

Through the creation of a mouse model, Dr. Genain will conclude whether single or repeated exposure to HHV-6 is necessary to develop disease, in addition to determining which HHV-6 variant(s) produce CNS demyelination, since his study in marmosets showed that only variant A induced MS-like pathology.  Finally, the study will aid in establishing the course of CNS associated disorders, and possibly identify different disease phenotypes (e.g. acute, chronic-relapsing, progressive) respectively associated with the two HHV-6 variants.

The potential impact of this study is extremely high. A mouse model that mimics MS after exposure to a human virus will greatly accelerate the discovery of causal links between HHV-6 exposure and disorders like MS. Specifically, if Dr. Genain and his team are successful in producing CNS disease in the mice, it will open the door to further investigation of association between HHV-6 and autoimmune demyelination. To date, Dr. Genain has successfully infected CD46 transgenic mice with both HHV-6 variants. These preliminary results will be used to apply for more substantial federal grants.

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