However, 51% of the sequences (14,667 of 28,451) were divided between five different isolates in roughly equal numbers. GBV-C is known to vary extensively between isolates and the large diversity revealed here indicates that these four affected twins were infected by different isolates and that different variants are present in each individual. Hepatitis C virus A standard diagnostic serology test confirmed previously unrecognized hepatitis C infection in one affected twin. This discovery provides a plausible medical explanation for chronic
fatigue in this individual. Discussion We used an “”unbiased”" genomic technology to Proteases inhibitor search for the presence of known and novel viruses that correlate with the clinical presence or absence of chronic fatiguing illness. Such searches have proven powerful for respiratory infections selleck chemicals llc [14, 15], and complement studies targeting specific infectious agents . The general hypothesis we tested was that chronic fatigue was associated with on-going viremia. As we have argued elsewhere , the study of discordant monozygotic twins was optimal in controlling for potential biases particularly as samples were obtained from both twins
at the same place and time. The deep Roche 454 sequencing, combined with the efficient enrichment of virus particles, makes it likely that most viruses present in the serum of these individuals were detected. However, we did not detect any clear-cut signatures of novel viruses. For known viruses, the predominant finding was a slight but significant excess of detection of nucleic acid from GBV-C in 8.9% of affected twins
and 0% of their unaffected co-twins (p = 0.019). Previously undetected hepatitis C virus infection was discovered in one affected twin. This individual was kept in these analyses as this is conservative and conforms to our prior intentions. GBV-C (also known as hepatitis G virus) is an RNA virus and member of the Flaviviridae family with greatest homology O-methylated flavonoid to hepatitis C virus. It is transmitted via multiple modalities (e.g., vertically, sexually, and parenterally) . GBV-C viremia is present in ~2% of healthy blood donors and 17% show evidence of past infection . GBV-C infection is not known to cause any human disease  and co-infection might improve the course of HIV-1 disease . A prior small study of 12 CFS cases and 21 controls concluded that chronic GBV-C infection was not associated with CFS . The lack of GBV-C positive individuals among the unaffected twins is could at first glance be seen as surprising. However, we would statistically expect that one or two individuals would be positive, based on chance, and the result we obtained is therefore not unlikely. There are several reasons why a chronic infection important to the etiology of chronic fatiguing illness could have escaped detection.