The finding that a retrovirus, XMRV, is associated with chronic fatigue syndrome has lead to the suggestion that the disease might be treated with some of the antiviral drugs used to treat AIDS. The integrase inhibitor Raltegravir has been found to block the replication of murine leukemia virus, which is highly related to XMRV. But the drug exacerbates autoimmune disease in mice which might rule out its use in treating CFS.
Retroviruses such as XMVR and HIV-1 have genomes composed of single-stranded RNA. This nucleic acid is converted to a DNA copy in infected cells by the viral enzyme reverse transcriptase. The double-stranded viral DNA is then integrated into the chromosomal DNA of the host cell, a process accomplished by an viral enzyme called integrase (illustrated).
Raltegravir (pictured above left) is an inhibitor of HIV-1 integrase that was approved for use in humans in 2007. The drug blocks the integration of viral DNA into the host genome and therefore inhibits viral replication.
The mouse retrovirus murine leukemia virus (MLV) has been linked to the development of spontaneous autoimmune disease. The mechanism by which the virus induces this disease is not known, but stimulation of innate immune responses by viral DNA might be involved.
Raltegravir also inhibits integration of MLV DNA into the murine genome. When mice with autoimmune disease were treated with raltegravir, they succumbed to autoimmune disease a month earlier than untreated animals. Mice without the disease were not affected by the antiviral drug. The authors speculate that by inhibiting viral DNA integration, raltegravir increases the amount of unintegrated viral DNA, elevating innate responses and exacerbating autoimmunity.
It’s not known if raltegravir is active against XMRV, the retrovirus associated with chronic fatigue syndrome. Given the similarity between the genomes of MLV and XMRV it seems likely that the drug will inhibit the virus. If the ability of raltegravir to treat CFS is tested in clinical trials, it will be important to carefully monitor treated patients for signs of autoimmunity. CFS has an autoimmune component which could worsen with raltegrivir treatment.
An obvious question is whether raltegrivir induces autoimmunity in AIDS patients. I’m not aware of any such reports, which is probably not surprising given the fact that HIV-1 infection leads to immunosuppression.
CFS sufferers should not despair: other antiretroviral drugs, including chain terminators such as AZT, do not allow the accumulation of unintegrated viral DNA. These compounds might be useful for treating the disease.
G.B. Beck-Engeser, D. Eilat, T. Harrer, H.-M. Jack, M. Wabl (2009). Early onset of autoimmune disease by the retroviral integrase inhibitor raltegravir Proceedings of the National Academy of Sciences : 10.1073/pnas.0908074106