Novel Treatment of Viral Infections

We propose a novel approach to prevention and/or treatment of viral infections. New approaches targeting host mechanisms rather than the virus themselves are required to provide better prevention and treatment alternatives. Transcriptional control of IFN-gene expression plays a major role in the activation of the innate immune response whereas translational control is critical for induction of type-1 IFN production which is the first line of antiviral defense. Inhibition of the expression and/or activity of 4E-BPs leads to induction or enhancement of the immune response as determined by increased expression of type-1 IFN.  This results in dramatically suppressed viral replication and resistance to viral infections, both in cultured cells lacking 4E-BP 1 and 2 and in 4E-BP 1/2 double knockout mice.  Similar results were obtained in cultured cells with RNA interference (RNAi) technology proprietary to McGill.    The wide application of this novel approach was validated using several different viruses: VSV, Sindbis, encephalomyocarditis, influenza, HIV-1, Herpes simplex 1 and myxoma.

Prevention and treatment of viral infections.

Serious viral infections are responsible for high rates of mortality and morbidity as well as high costs to the healthcare system worldwide. There are no prophylactic vaccines or curative treatments for HIV and in the case of influenza new vaccines with limited efficacy have to be developed each year confirming unmet medical needs.  It is estimated that AIDS has killed more than 25 million people since it was first recognized in 1981 whereas according to the WHO, influenza yearly affects 3 to 5 million people worldwide and results in 250-500,000 deaths. The current market for antiviral drugs is over $12 billion and is projected to reach in excess of $20 billion by 2012. Utilization of an effective antiviral therapy to treat serious viral infections such as HIV, HCV and influenza could be expanded to limited but deadly infections like Avian influenza and Ebola virus as well as to other diseases where a viral component is suspected, thereby further increasing the market potential.