16 - Surface Antigenic Variation in Giardia Lamblia

Abstract

Giardia lamblia (G. lamblia) is a binucleated and intestinal-dwelling flagellate that is the cause of diarrhea and intestinal upset worldwide. It is also one of the earliest diverging eukaryotes and has a simple fecal-oral life cycle. Unlike other organisms where surface antigenic variation was suggested by the biology of the organism in the host, antigenic variation was unsuspected in G.lamblia and was discovered as an in vitro phenomenon. This chapter reviews the surface antigenic variation that occurs spontaneously in vitro in Giardia lamblia. Antigenic variation in vitro was initially suggested by varying surface-labelling patterns of cultures over time but was definitively demonstrated with the development of variant surface proteins (VSP) specific to cytotoxic monoclonal antibodies. The dynamics of VSP switching are superficially and mechanistically similar to other parasites that undergo antigenic variations. The propensity to switch VSPs in culture is strain-dependent and VSP-dependent and ranges from about 6.5 generations to 13 generations until VSP switching occurs. Surface antigenic variation in G. lamblia is unique. However, the major questions about the phenomenon remain unanswered, such as biologic role of antigenic variation, the way in which the unique structure of VSPs help the parasite, and the way this unique structure contribute to the pathophysiology of disease. The ability to transfect Giardia, use of appropriate animal models, detailed studies of human infection, and knowledge of VSP genomic organization may probably lead to a better understanding of antigenic variation process in Giardia.