Recombinant Origin of the Retrovirus XMRV: Discovery, Analysis and Distribution of Two Ancestral Viruses.
murine leukemia virus-related virus (XMRV) is a retrovirus, initially reported to be
associated with human prostate cancer and chronic fatigue syndrome, although these
findings have not been replicated. XMRV bears high sequence identity to a class of mouse
retroviruses, called murine leukemia viruses (MLVs). We sought to determine the origin
of XMRV and how it may have cr... read moreossed species to infect the human population. Our work
showed that XMRV was created through recombination between two endogenous MLVs, named
PreXMRV-1 and PreXMRV-2, and that the recombination event that gave rise to XMRV
occurred in the laboratory, during passaging of a prostate tumor xenograft in nude mice.
The probability of generating the exact same recombinant more than once and
independently is negligible, suggesting that all XMRV isolates described to date are
derived from this unique recombination event. Furthermore, XMRV is not present as a
single endogenous provirus in any of the wild or laboratory mouse strains tested. The
strain distribution of PreXMRV-1 and PreXMRV-2 are quite different, making it unlikely
that the two XMRV ancestors could have recombined independently in the wild to generate
an infectious virus. Our results show that the association of XMRV with human disease is
due to contamination of laboratory assays with virus originating from the initial
Thesis (Ph.D.)--Tufts University, 2012.
Submitted to the Dept. of Genetics.
Advisor: John Coffin.
Committee: Phil Hinds, Naomi Rosenberg, and Gavin Schnitzler.
Keywords: Biology, Genetics, and Virology.read less