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Raltegravir exacerbates mice autoimmune disease; might rule out use in treating CFS.


kelly posted this reminder (from Nov 09) to CO-CURE today

[Note: The PLos study regarding the implications of anti-viral use, should
XMRV be proven pathogenic in humans, also brings up an immune issue found
with one of the drugs studied which was published in late 2009.]

Raltegravir inhibits murine leukemia virus: implications for chronic fatigue

by Vincent Racaniello on 20 November 2009

[image: Raltegravir]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).

[image: retroviral_integration]

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 <http://www.virology.ws/2009/06/03/innate-immune-defenses/> 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.

Its 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. Im 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 :

I learned very early the difference between knowing the name of something
and knowing something.

Richard Feynman The Physics Teacher Vol. 7, issue 6 (1969)



Senior Member
Yeah, I had come across this a while back but I thought the fact that they used mice specifically created with an autoimmune disease already made a difference in how these results came out. Mice without an autoimmune disease did not have these issues. I also read somewhere else (can't find it now) that the drug might actually help certain autoimmune illnesses but not others.


Senior Member
Clay, Alabama
I would love to hear Klimas' reaction to this. She knows immune system best.

Think this very issue reflects the circular nature of our immune system trying to recover from infection. Whether helped by retrovirus or just natural defense.



Senior Member
Does it cause autoimmune disease in humans with HIV that take it? Or has it not been out long enough to tell?

cfs since 1998

Senior Member
Vincent Racaniello claims CFS "has an autoimmune component" but I have not seen any evidence of that. It seems autoimmune conditions are more common in CFS but I don't think it is an autoimmune disease in and of itself. I do not have any autoimmune issues. Also it says "exacerbates" autoimmune disease; that's a bit different from causing one where there wasn't before.