A beginner's guide to the RNase L pathway

Viral infections stimulate the production of cytokines, including the interferons. Interferons control the way in which cells respond to a virus through their effect on a group of inter-related enzymes that make up an antiviral defense pathway.  (For those of you who like details, the latter goes by the name of the 2-5A synthetase/ribonuclease L pathway).

The status of the RNase L pathway, as I'll refer to it here, is measured in humans by taking a sample of blood and separating the lymphocytes (white blood cells). RNase L is the key enzyme. It's 'turned on' by a small molecule, 2-5A.  This changes the enzyme from its inactive state to its active state. When active, RNase inhibits the synthesis of viral protein and thereby prevents the virus from replicating.

Research in the States has found that several parts of the pathway are clearly not functioning properly in many patients with CFS. For instance, people who became ill during the epidemic at Lake Tahoe (and developed ME) had a dramatically increased level of RNase L activity (as much as 1500 times above normal). * Conversely, as their symptoms improved, their RNase L activity decreased.

Blood samples from patients with CFS have also revealed other abnormalities, for instance, a significant increase in 2-5A, (the molecule that 'turns on' RNase L), and a second enzyme involved in the pathway.  However, the most striking finding has been the discovery of a unique form of RNase L.

The size of the normal form of RNase L is 80 kilodaltons (kDa). However, patients with CFS often have another form with a lower molecular weight: 37 kDa. Despite its smaller size, it's more potent than the 80 kDa form.

Finally, the research so far has shown that the three abnormalities in the antiviral pathway (RNase L, the levels of 2-5A, and the low molecular form of RNase L) are all linked to a lower state of general health. In other words, these findings are of clinical significance!

*While the antiviral pathway is active, it consumes adenosine triphosphate (ATP), the cells' energy source, which could lead to some of the symptoms of CFS.

With thanks to Nancy Reichenbach, CFS Research Review, 2000, 1, 1, 1-3. (CFIDS Association, USA).