Frequent loss of the active site during variant surface glycoprotein expression site switching in vitro in Trypanosoma brucei.

Molecular and Cellular Biology
M CrossP Borst

Abstract

African trypanosomes undergo antigenic variation of their variant surface glycoprotein (VSG) coat to avoid being killed by their mammalian hosts. The active VSG gene is located in one of many telomeric expression sites. Replacement of the VSG gene in the active site or switching between expression sites can give rise to a new VSG coat. To study Trypanosoma brucei VSG expression site inactivation rather than VSG gene switching, it is useful to have an in vitro negative-selection system independent of the VSG. We have achieved this aim by using a viral thymidine kinase (TK) gene. Following integration of the TK gene downstream of the 221a VSG expression site promoter, transformant cell lines became sensitive to the nucleoside analog 1-(2-deoxy-2-fluoro-8-D-arabinofuranosyl)-5-iodouracil. These TK trypanosomes were able to revert to resistance at a rate approaching 10(-5) per cell per generation. The majority of revertants expressed a new VSG gene even though there had been no selection against the VSG itself. Analysis of these switched variants showed that some had shut down TK expression via an in situ expression site switch. However, most variants had the complete 221 expression site deleted and another VSG expression site acti...Continue Reading

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Citations

Jul 28, 2009·Trends in Parasitology·Richard McCulloch, David Horn
Aug 4, 2004·Current Opinion in Microbiology·Etienne PaysDavid Pérez-Morga
Oct 28, 2008·PloS One·Christiane Hertz-FowlerMatthew Berriman
Jul 31, 2009·Annual Review of Genetics·Kevin J Verstrepen, Gerald R Fink
Oct 17, 2002·Annals of the New York Academy of Sciences·Filip ClaesP Buscher
Jun 12, 2002·Transactions of the Royal Society of Tropical Medicine and Hygiene·Guoliang Fu, Sara E Melville
May 4, 2001·International Journal for Parasitology·G A Cross
Feb 1, 2003·Health Marketing Quarterly·William R GombeskiJeff Wack
Jun 26, 2001·Trends in Parasitology·L VanhammeJ D Barry
Feb 13, 2001·Molecular and Biochemical Parasitology·S E MelvilleG A Cross

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African trypanosomiasis, also known as sleeping sickness, is an insect-borne parasitic disease of humans and other animals. It is caused by protozoa of the species Trypanosoma brucei and almost invariably progresses to death unless treated. Discover the latest research on African trypanosomiasis here.