Development of a Broad-Spectrum Antiviral Agent

Among the research projects within the Multiple Sclerosis Laboratory of Moses Rodriguez, M.D., is one investigating vaccine resistance to viruses and resistance to autoimmune diseases.

The project, called Development of a Broad-Spectrum Antiviral Agent, grew out of concern about the global health threat posed by viruses.

Of primary concern is that pharmaceuticals are not available for the majority of naturally emerging or bioterrorism-engineered viruses. The limited success of vaccines and inhibitory drugs as antiviral therapeutics necessitates more novel approaches. Modulation of cellular antiviral defense mechanisms provides an approach to exploit endogenous signaling cascades for therapeutic benefit.

Dr. Rodriguez's team of investigators recently discovered that transgenic expression of the Theiler's Murine encephalomyelitis virus (TMEV) gene, 3-D polymerase, in FVB mice results in a mouse that is resistant to virus infections.

These FVB-3D mice are able to withstand lethal challenges with encephalomyocarditis virus (ECMV), which causes fatal heart disease in humans. In addition, the mice survived infection with herpes viruses, which can cause a variety of disabling diseases in humans, including fatal encephalitis.

Further, the mice survived infection with vesicular stomatitis virus, which is typically transmitted by insects and causes ulcers in the mouths of animals.

The point of infecting with these different groups of viruses was to prove that the mice can withstand infections with both RNA and DNA viruses.

Resistance to this lethal virus challenge is the result of transgenic expression of 3-D initiating expression of prominent antiviral response genes in all organ groups. Another remarkable feature of the FVB-3D mice is that despite constitutive expression of type I interferon responsive genes, these animals are devoid of autoimmunity.

These mice breed perfectly well in the laboratory and live a normal life span without diseases. They're phenotypically normal, except for being highly resistant to virus infection.

The summation of these results is now published in PLOS Pathogens.

Significance to patient care

The major significance to patient care with this research project in Dr. Rodriguez's Multiple Sclerosis Laboratory is that understanding how these mice fight off infection might provide insight into how to generate a vaccine that could function against all viruses in the world. Since research shows that the gene that was inserted in these mice create the response, it's likely that the Rodriguez lab can generate a similar strategy in humans either before or after potentially lethal virus infections.

Another potential outcome is gaining an understanding of why these mice don't develop autoimmune disease.

The dogma in science is that up-regulation of these antiviral genes such as the natural interferons causes many autoimmune diseases in experimental animals and possibly in humans. Since these mice don't develop autoimmunity, it provides a unique opportunity to understand why this doesn't occur.

Understanding these basic concepts could one day lead to a cure for autoimmunity.