Materials and methods for prevention and treatment of RNA viral diseases
The subject invention concerns a method of inhibiting an RNA virus infection within a patient by increasing the amount of 2-5 oligoadenylate synthetase (2-5 AS) activity within the patient. Preferably, the preventative and therapeutic methods of the present invention involve administering a nucleotide encoding 2-5 AS, or at least one catalytically active fragment thereof, such as the p40, p69, p100 subunits, to a patient in need thereof. The present inventors have determined that overexpression of 2-5AS causes a reduction in epithelial cell damage, reduction in infiltration of mononuclear cells in the peribronchiolar and perivascular regions, and reduction in thickening of the septa in the lungs. Levels of chemokines, such as MIP1-α, are also reduced upon overexpression of 2-5AS. The subject invention also pertains to pharmaceutical compositions containing a nucleotide sequence encoding 2-5 AS and a pharmaceutically acceptable carrier, as well as vectors for delivery of the 2-5 AS nucleotide sequence.
1. A method of increasing expression of 2′-5′ oligoadenylate synthetase in a mammal, said method comprising administering to the mammal a nucleotide sequence encoding a 2′-5′ oligoadenylate synthetase, or at least one enzymatically active fragment thereof, wherein the nucleotide sequence is expressed in the mammal.
2. The method of claim 1 , wherein the enzymatically active fragment comprises an enzymatically active subunit of 2′-5′ oligoadenylate synthetase selected from the group consisting of p40, p69, and p100.
3. The method according to claim 1 , wherein the nucleotide sequence is administered to the mammal within a viral vector.
4. The method of claim 1 , wherein the nucleotide sequence is administered to the mammal intranasally.
5. The method of claim 1 , wherein the expression of 2′-5′ oligoadenylate synthetase is increased to treat infection of the mammal by an RNA virus, and wherein the RNA virus is a type that transiently produces double-stranded RNA during intermediate replication.
6. The method of claim 5 , wherein the mammal is a human.
7. The method of claim 6 , wherein the human is a child.
8. The method of claim 6 , wherein the human is elderly.