Xenotropic Murine Leukemia Virus-related Virus - History

History

XMRV was discovered by laboratories led by Joseph DeRisi at the University of California, San Francisco, and Robert Silverman and Eric Klein of the Cleveland Clinic. Silverman had previously cloned and investigated the enzyme ribonuclease L (RNase L), part of the cell’s natural defense against viruses. When activated, RNase L degrades cellular and viral RNA to halt viral replication. In 2002, the "hereditary prostate cancer 1" locus (HPC1) was mapped to the RNase L gene, implicating it in the development of prostate cancer. The cancer-associated "R462Q" mutation results in a glutamine instead of an arginine at position 462 of the RNase L enzyme, reducing its catalytic activity. A man with two copies of this mutation has twice the risk of prostate cancer; one copy raises the risk by 50%.

Klein and Silverman hypothesized that "the putative linkage of RNase L alterations to HPC might reflect enhanced susceptibility to a viral agent", leading to the discovery of XMRV.

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