Differentiation-associated surface antigen variation in the ancient eukaryote Giardia lamblia

Encystation of Giardia lamblia is required for survival outside the host, w hereas excystation initiates infection. The dormant cyst was considered an adaptation to external survival and passage through the stomach. However, w e found previously that trophozoites which had recovered after completion o f the life cycle had switched their major variant surface protein (VSP), ca lled TSA 417, but neither the timing nor the molecular mechanism of switchi ng had been elucidated. Here we demonstrate that TSA 417 predominates in cy sts, but is downregulated during the stage of excystation that models cyst arrival in the small intestine. Transcripts of new VSPs appear late in ency station, and during and after excystation. Trophozoites appear to prepare f or switching during encystation, when the major VSP on the cell surface dim inishes and is internalized in lysosome-like vacuoles. As short-range DNA r earrangements were not detected, giardial VSP switching during differentiat ion appears to resemble the in situ switching of surface glycoproteins in A frican trypanosomes. We also report a unique extended 15 nucleotide polyade nylation signal in all VSP transcripts, but not in other known giardial gen es. Antigenic variation during encystation-excystation may be a novel form of immune evasion that could help explain the common occurrence of reinfect ion by Giardia and other parasites with similar life cycles.