title: Antigenic variation in Giardia lamblia is regulated by RNA interference.
abstract: Giardia lamblia (also called Giardia intestinalis) is one of the most common intestinal parasites of humans. To evade the host's immune response, Giardia undergoes antigenic variation-a process that allows the parasite to develop chronic and recurrent infections. From a repertoire of approximately 190 variant-specific surface protein (VSP)-coding genes, Giardia expresses only one VSP on the surface of each parasite at a particular time, but spontaneously switches to a different VSP by unknown mechanisms. Here we show that regulation of VSP expression involves a system comprising RNA-dependent RNA polymerase, Dicer and Argonaute, known components of the RNA interference machinery. Clones expressing a single surface antigen efficiently transcribe several VSP genes but only accumulate transcripts encoding the VSP to be expressed. Detection of antisense RNAs corresponding to the silenced VSP genes and small RNAs from the silenced but not for the expressed vsp implicate the RNA interference pathway in antigenic variation. Remarkably, silencing of Dicer and RNA-dependent RNA polymerase leads to a change from single to multiple VSP expression in individual parasites.
authors.affiliation: Laboratorio de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Católica de Córdoba, Córdoba X5004ASK, Argentina.
authors.forename: César G
authors.initials: CG
authors.lastname: Prucca
authors.forename: Ileana
authors.initials: I
authors.lastname: Slavin
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Quiroga
authors.forename: Eliana V
authors.initials: EV
authors.lastname: Elías
authors.forename: Fernando D
authors.initials: FD
authors.lastname: Rivero
authors.forename: Alicia
authors.initials: A
authors.lastname: Saura
authors.forename: Pedro G
authors.initials: PG
authors.lastname: Carranza
authors.forename: Hugo D
authors.initials: HD
authors.lastname: Luján
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000940:Antigenic Variation / Q000235:genetics* / Q000276:immunology; D000953:Antigens, Protozoan / Q000235:genetics* / Q000276:immunology; D000954:Antigens, Surface / Q000235:genetics* / Q000276:immunology; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D016829:Giardia lamblia / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology; D034622:RNA Interference; D016053:RNA, Protozoan / Q000378:metabolism; D043244:Ribonuclease III / Q000378:metabolism
chemical_list: D000953:Antigens, Protozoan; D000954:Antigens, Surface; D015800:Protozoan Proteins; D016053:RNA, Protozoan; D043244:Ribonuclease III