In the linked case-control study (doi:10.1136/bmj.c1018), van Kuppeveld and colleagues describe their failure to find evidence of a new human retrovirus in Dutch patients with chronic fatigue syndrome.1 The study is the latest contribution to a controversy that has surrounded two conflicting publications on the retroviral aetiology of this syndrome.2 3

The saga started, not with chronic fatigue syndrome or a virus, but with an enzyme (RNaseL) that plays a pivotal role in antiviral defences when activated by the interferon released in response to infection. Variants of the gene encoding this enzyme have been linked to an increased susceptibility to prostate cancer, and this led to the identification of a new virus in prostate tissue that was related to, but different from, known xenotropic murine leukaemia viruses4; hence the designation xenotropic murine leukaemia virus-related virus (XMRV). Sequence analyses showed that it is not an endogenous human virus, and the fact that eight clones derived from eight different patients are slightly different from one another confirms it as a new virus that has …