It has been known for years that patients with chronic fatigue syndrome (CFS) have a defect in a major antiviral pathway, the 2-5A/RNase L pathway. The RNaseL produces non-specific viral cleavage and, thus, protects us from many viral infections (innate immunity). Defects in this pathway not only lead to susceptibility to viral infections but may also increase our susceptibility to tumor development. The RNaseL gene, called Human Prostate Cancer 1 (HPC1), has a variant R462Q related to a potential etiologic agent of prostate cancer, a novel human retrovirus, xenotropic murine leukemia virus (MuLV), named XMRV. So, it was by a bit of serendipity that a group of workers headed by several from the Whittemore Peterson Institute in Reno, Nevada, asked if XMRV could be associated with CFS. What led to any rationale connection between prostate cancer and CFS is not clear, but the question led to a series of experiments that culminated in a very recent publication showing an association between the presence of this retrovirus in the peripheral blood mononuclear cells (PBMCs) of patients with CFS. We are dealing here with intricate science that surely took these 13 scientists and a host of technicians years to produce. Yet the paper contains astounding findings that I'll try to summarize succinctly, for besides the eight primary article pages from Science Express, there are 18 additional pages of "supporting" materials that also contain fascinating data. Here is what the paper reports. In 101 banked samples of PBMCs, 67% (68) were positive for a XMRV gag sequence. Next, seven of 11 PBMC CFS samples held at the Cleveland Clinic were shown to have XMRV gag plus env. Only 3.7% of PBMC DNA from healthy controls had XMRV gag when tested by PCR. Amazingly, those gag and env sequences were nearly identical to those from XMRV from prostate cancer-associated strains (PLoS Pathol. 2006;2:211). Full-length SMRV from two patients differed from prostate cancer strain VP62 by only six nucleotides, showing again a > 99% identity between the CFS and prostate cancer XMRV. A phylogenetic comparison of six isolates from CFS/Prostate cancer showed them to be significantly different from other murine leukemic viruses. In all, 50 other isolates of MLV were used to make the neighbor-joining trees. The suspected closest relatives were other xenotropic murine viruses (Xmv 15-19 and Xmv 10, 13, 16) and polytropic (Pmv) plus modified polytropic (Mmpv) viruses, which were in fact very removed genetically from XMRV. Next, it was shown that several antibodies with "novel viral specificities" all reacted with VP62 XMRV proteins when grown in several cell lines, including a line called LNCaP of prostate cells that are known to permit infection with MXRV. Flow cytometry of activated lymphocytes also showed that 19 of 30 PBMC CFS samples reacted with antibodies to MLV P30 Gag and other MLV proteins whereas PBMCs from normal patients were negative, for an odds ratio of 54.1. (confidence intervals of 23.8-122). So, there is a non-random association of CFS PBMCs with XMRV. Both activated T and B cells from CFS were infected with XMRV. The next experiment was quite ingenious. PBMCs from CFS patients were co-cultured with LNCaP cells, the ones defective in RNaseL pathways. The LNCaP cells became infected, as shown by presence of XMRV gag and env proteins and by the presence of whole virus, as seen by electron microscope both at the time of infection and upon release. The electron micrographs are quite stunning. The same type of infectivity was also seen when only plasma from CFS patients was applied to LNCaP cells. Thus, cell-associated and cell-free virus seems to be infectious, at least to some cell lines. Finally, it was shown that 50% of plasma samples from patients with CFS have a humoral response to XMRV, demonstrated by presence in flow cytometry assays of antibodies to a viral env closely related to XMRV env. [ABSTRACT FROM AUTHOR]