Early onset of autoimmune disease by the retroviral integrase inhibitor raltegravir
Early onset of autoimmune disease by the retroviral integrase inhibitor raltegravir
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DOI：
10.1073/pnas.0908074106
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发表时间：
2009-12-08
影响因子：
11.1
通讯作者：
Wabl，Matthias
中科院分区：
文献类型：
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作者：
Beck-Engeser，Gabriele B.;Eilat，Dan;Wabl，Matthias
Raltegravir is a recently, Food and Drug Administration-approved, small-molecule drug that inhibits retroviral integrase, thereby preventing HIV DNA from inserting itself into the human genome. We report here that the activity profile of raltegravir on the replication of murine leukemia virus is similar to that for HIV, and that the drug specifically affects autoimmune disease in mice, in which endogenous retroelements are suspected to play a role. While NZW and BALB/c mice, which do not succumb to autoimmune disease, are not affected by raltegravir, lupus-prone (NZBxNZW) F1mice die of glomerulonephritis more than a month earlier than untreated mice. Raltegravir-treated NZB mice, which share the H-2 haplotype with BALB/c mice, but which are predisposed to autoimmune hemolytic anemia, develop auto-antibodies to their red blood cells >3 months earlier than untreated mice of the same strain. Because nonautoimmune mice are not affected by raltegravir, we consider off-target effects unlikely and attribute the exacerbation of autoimmunity to the inhibition of retroviral integrase.
