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

HUGO DANIEL LUJÁN

Buenos Aires

Congreso; X Congreso Argentino de Microbliología; 2004

Asociación Argentina de Microbiología

Giardia lamblia is one of the most common intestinal parasites of humans and a 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 (VSP), from a repertoire of approximately 150 vsp genes, is expressed on the surface of every single Giardia trophozoite, but switching to the expression of a distinct VSP occurs even in absence of any immune pressure. In this work we demonstrate that vsp expression is post-transcriptionally regulated by a cellular mechanism displaying 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 detected for the silenced but not for the expressed vsp. Proteins homologue to components of post-transcriptional gene silencing (PTGS) machineries of higher eukaryotes, including an RNA-dependent RNA-polymerase, modules of Dicer (a bidentate RNase III and a RNA DEAD-box helicase), PIWI/Argonaute, and SN/Tudor, are expressed during the entire life cycle of Giardia. Moreover, knock-down of these enzymes leads to a change from single to multiple VSP expression in individual trophozoites. These results are consistent with the involvement of a PTGS mechanism in regulating antigenic variation of this important human pathogen.