Variant-specific surface proteins as mediators of antigenic variation in Giardia lamblia

MARTIN MARIA JULIA; TENAGLIA ALBANO H; LUJAN HUGO D; RIOS DIEGO N.; GARGANTINI PABLO R.

Córdoba

Congreso; 52 th Annual Meeting Argentine Society for Biochemistry and Molecular Biology; LII Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2016

Giardia lamblia colonizes the upper smallintestine of humans and other vertebrates causing giardiasis. Like manypathogenicmicroorganisms, Giardia undergoes antigenic variation (AV), a processthat contributes to the production of chronic and/or recurrentinfections. Thesurface of Giardia trophozoites is covered by a dense coat of Variant-specificSurface Proteins (VSPs), whichrepresents the interface between the parasite andthe environment. Giardia possesses ~200 VSP genes, but only one VSP isexpressedon its surface at a particular time. The stimulus that triggers VSPswitching is unknown. VSP are integral membrane proteinscomprising a variableextracellular domain and a highly conserved C-terminal region includingtransmembrane domain and a shortcytoplasmic tail. In this work, we show thatanti-VSP immunoglobulins (Igs) are not cytotoxic to Giardia, as previouslyreported, butthey increase the rate of VSP switching. Besides, we prove thatanti-VSP Igs increase the Giardia reduced state, which could be linkedto theinitiation of a still unclear intracellular signal triggered by the presence ofthe anti-VSP Igs. By using fragmented anti-VSP Igsand point mutations in theconserved C-terminal domain of VSPs, we demonstrate that AV in Giardia is acomplex mechanisminvolving both external and cellular processes linked by theparticular structure of the VSPs.