Mutually exclusive expression of virulence genes by malaria parasites is regulated independently of antigen production

PLoS Pathogens
Ron DzikowskiKirk Deitsch

Abstract

The primary virulence determinant of Plasmodium falciparum malaria parasite-infected cells is a family of heterogeneous surface receptors collectively referred to as PfEMP1. These proteins are encoded by a large, polymorphic gene family called var. The family contains approximately 60 individual genes, which are subject to strict, mutually exclusive expression, with the single expressed var gene determining the antigenic, cytoadherent, and virulence phenotype of the infected cell. The mutually exclusive expression pattern of var genes is imperative for the parasite's ability to evade the host's immune response and is similar to the process of "allelic exclusion" described for mammalian Ig and odorant receptor genes. In mammalian systems, mutually exclusive expression is ensured by negative feedback inhibition mediated by production of a functional protein. To investigate how expression of the var gene family is regulated, we have created transgenic lines of parasites in which expression of individual var loci can be manipulated. Here we show that no such negative feedback system exists in P. falciparum and that this process is dependent solely on the transcriptional regulatory elements immediately adjacent to each gene. Transge...Continue Reading

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Citations

Apr 3, 2014·Cellular and Molecular Life Sciences : CMLS·Jo-Anne ChanJames G Beeson
May 22, 2008·Malaria Journal·Christian EppKirk W Deitsch
Jun 14, 2008·PLoS Pathogens·Christiaan van OoijKasturi Haldar
Feb 27, 2009·Current Genetics·Ron Dzikowski, Kirk W Deitsch
Aug 8, 2009·BMC Genomics·Nicolas SmargiassoAntoine Claessens
Apr 24, 2013·Molecular Biology and Evolution·Thomas W SchoenfeldBrian P Hedlund
Apr 14, 2010·Wiener klinische Wochenschrift·Matthias Frank, Corinna Enderes
Mar 27, 2012·The Journal of Infectious Diseases·Catherine J MerrickManoj T Duraisingh
Mar 23, 2013·Nucleic Acids Research·Anne Katrine Alsing, Kim Sneppen
Sep 13, 2008·Annual Review of Microbiology·Artur ScherfLoïc Riviere
Feb 13, 2016·Parasitology·Karina P De Sousa, Denise L Doolan
Sep 6, 2008·Trends in Parasitology·Thanat ChookajornLiwang Cui
Mar 14, 2007·Trends in Parasitology·Michael F Duffy, Wai-Hong Tham
Aug 28, 2009·Molecular Microbiology·Cali A HowittKirk W Deitsch
Jul 19, 2008·Cellular Microbiology·Bradley I Coleman, Manoj T Duraisingh
Jun 9, 2007·Molecular Microbiology·Matthias FrankKirk Deitsch
Nov 2, 2006·Molecular Microbiology·Catherine J Merrick, Manoj T Duraisingh

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Methods Mentioned

BETA
transgenic
PCR
transfection
electrophoresis

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