An antisense RNA silencing system regulates surface antigen expression in the intestinal parasite Giardia lamblia

HUGO DANIEL LUJÁN

Rosario- Santa Fe

Congreso; XX Reunion Anual de la Sociedad Argentina de Protozoologia; 2004

Sociedad Argentina de Protozoologia

Giardia lamblia is one of the most common intestinal parasites of humans and major cause of sporadic and endemic diarrhea worldwide.Chronic infections are caused by the parasite´s capability to change its surface antigens .Only one variant-specific surface protein, from a repertoire of aproximately 150 vsp genes, is expressed on the surface of every single Giardia trophozoite, butswitching to the expression of a distinct VSP occurs even in absence of any immune pressure.We demonstrated that VSP expression is post-transcritionally regulated by a cellular mechanismdisplaying features of RNAi. Giardia clones expressing a single surface antigen efficiently transcribe several other vsp but only accumulate transcripts encoding the actual VSP. Antisense vsp transcripts and their corresponding small 25-nt-long RNAs are delected for the silenced but not for the expressedvsp. Proteins homologue to components of post-transcriptional gene silencing machinaries of higher eukaryotes, including an RNA-depend RNA-polymerase,modules dicer,PIWI/argonaute, and SN/Tudor, are expressed duringthe entire life cycle of Giardia. Moreover, knock-down of these enzymes leads to a changes from single to multiple VSP expression in individual trophozoites.These results are consistent with the involvementof a PTGS mechanism in regulating antigenis variation of this important human pathogen.