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Viral Recombination00:57

Viral Recombination

Cells are sometimes infected by more than one virus at once. When two viruses disassemble to expose their genomes for replication in the same cell, similar regions of their genomes can pair together and exchange sequences in a process called recombination. Alternatively, viruses with segmented genomes can swap segments in a process called reassortment.
Viral Mutations00:36

Viral Mutations

A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material for adaptive...

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Disease-associated XMRV sequences are consistent with laboratory contamination.

Stéphane Hué1, Eleanor R Gray, Astrid Gall

  • 1MRC Centre for Medical Molecular Virology, Division of Infection and Immunity, University College London, 46 Cleveland St, London W1T 4JF, UK.

Retrovirology
|December 22, 2010
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Summary

Xenotropic murine leukaemia virus-related virus (XMRV) detection in patients may be due to mouse DNA contamination. The study suggests XMRV may not be a human pathogen, potentially originating from cell line contamination.

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Area of Science:

  • Virology
  • Molecular Biology
  • Genetics

Background:

  • Xenotropic murine leukaemia viruses (MLV-X) are endogenous gammaretroviruses with broad host tropism.
  • Xenotropic murine leukaemia virus-related virus (XMRV) detection in human samples (prostate cancer, chronic fatigue syndrome) has been controversial due to inconsistent findings.

Purpose of the Study:

  • To investigate the origin and validity of XMRV detection in human samples.
  • To determine if XMRV is a genuine human pathogen.

Main Methods:

  • Utilized Taqman PCR with specific primers for XMRV detection.
  • Sequenced XMRV from the 22Rv1 cell line and patient samples.
  • Performed Bayesian phylogenetic analysis and genetic distance comparisons.
  • Analyzed pol and env gene sequences for recombination events.

Main Results:

  • XMRV-specific PCR primers amplified common murine endogenous viral sequences, indicating potential mouse DNA contamination.
  • Phylogenetic analysis showed XMRV sequences from patients formed a clade with 22Rv1 cell line sequences, with cell line sequences being ancestral.
  • Recombinant pol sequences were identified in patient samples, suggesting complex origins.
  • Greater genetic diversity was observed in XMRV sequences from the 22Rv1 cell line compared to patient-derived sequences.

Conclusions:

  • XMRV detection in patient samples is likely due to PCR contamination with mouse DNA.
  • Identified XMRV clones likely originated from the 22Rv1 tumor cell line, possibly infected during xenografting.
  • XMRV may not be a genuine human pathogen.