Regulation of Antigenic Variation in<i>Giardia lamblia</i>

Prucca, César G.; Rivero, Fernando; Luján, Hugo D.

doi:10.1146/annurev-micro-090110-102940

Cited by 50 publications

(55 citation statements)

References 151 publications

(151 reference statements)

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“…This wall contains fibrils of a homopolymer of N-acetylgalactosamine (N-AcGal) and at least three cyst wall proteins (CWP1, 2 and 3) [36]. The three CWPs are proteins showing high contents of cysteine, several leucine-rich repetition regions (LRR), a preserved and cysteine-rich C-terminal region (CRR) and several glycosylation and phosphorylation sites [80,81]. The genes in the CWPs are transcribed only during encystation, an increase of 140 times the transcribed levels being detected as compared to the non-encysting trophozoites [80,82,83].…”

Section: Parasite Morphology Cystmentioning

confidence: 99%

“…The three CWPs are proteins showing high contents of cysteine, several leucine-rich repetition regions (LRR), a preserved and cysteine-rich C-terminal region (CRR) and several glycosylation and phosphorylation sites [80,81]. The genes in the CWPs are transcribed only during encystation, an increase of 140 times the transcribed levels being detected as compared to the non-encysting trophozoites [80,82,83]. A fourth cyst wall protein (HCNCp) has just been discovered [80,81].…”

Section: Parasite Morphology Cystmentioning

confidence: 99%

“…The genes in the CWPs are transcribed only during encystation, an increase of 140 times the transcribed levels being detected as compared to the non-encysting trophozoites [80,82,83]. A fourth cyst wall protein (HCNCp) has just been discovered [80,81]. Molecular studies have shown this HCNCp protein is also positively regulated during encystation and is part of the cystic wall [84].…”

Section: Parasite Morphology Cystmentioning

confidence: 99%

“…The trophozoite contains around 200 genes codifying for a heterogeneous family of proteins called variant surface proteins (VSPs). These VSPs are comprehensive membrane proteins, rich in cysteine (11-12%), whose molecular masses range between 30 and 200 kDa [80]. The VSP genes are distributed among the 5 chromosomes and correspond to approximately 2% of the genome [9,36].…”

Section: Trophozoitementioning

confidence: 99%

“…Antigenic variation, or switching, consists of the continual switch of certain surface proteins in the trophozoite (VSP). Such spontaneous variation occurs both in vitro and in vivo and it is produced every 6-16 parasite generations [80]. The molecular mechanism involved in the antigenic variation is not fully clear.…”

Section: Host-parasite Interactionmentioning

confidence: 99%

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Antigenic Variation in Microbial Evasion of Immune Responses

Kotwal

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2013

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Antigenic variation is the means by which a number of highly pathogenic microorganisms, ranging from the electronmicroscopic human viruses to bacteria to fungi and unicellular protozoan parasites, passively evade immune surveillance. Through the understanding of the growing variety of mechanisms of the antigenic variation of surface proteins, it has become possible for us to determine what is preventing the host organism from mounting an effective immune response. Antigenic variation has serious public health consequences, for example, the current human immunodeficiency virus pandemic and the looming influenza pandemic, as well as a significant challenge to developing vaccines capable of eliciting long‐lasting or life‐long protective immunity against several pathogens. Key Concepts: Antigenic variation is a major mechanism of passively evading the host immune surveillance. Antigenic variation is exhibited by a number of highly pathogenic microorganisms including human viruses, bacteria, fungi and unicellular protozoans. Antigenic variation poses challenges to vaccine development against microorganisms causing major public health problems globally. HIV‐1 surface glycoproteins display antigenic variation due to a high mutation rate during replication and significant tolerance of the variation. Heterochromatin in the chromososome ends (telomers) in the malarial parasites mediate epigenetic regulation in the malaria parasite Plasmodium falciparum . African trypanosomes control antigenic variation by periodically switching its variant surface glycoprotein involving transposition followed by recombination occurring at the telomeric expression site. Targeting conserved regions of surface glycoproteins by using broadly neutralising antibodies against highly conserved exposed sites in surface proteins. Targeting the oligosaccharides on surface glycoproteins, such as by the use of enveloped virus neutralising compounds (EVNCs).

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Ubiquitination dynamics in the early‐branching eukaryote Giardia intestinalis

et al. 2013

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Ubiquitination is a highly dynamic and versatile posttranslational modification that regulates protein function, stability, and interactions. To investigate the roles of ubiquitination in a primitive eukaryotic lineage, we utilized the early-branching eukaryote Giardia intestinalis. Using a combination of biochemical, immunofluorescence-based, and proteomics approaches, we assessed the ubiquitination status during the process of differentiation in Giardia. We observed that different types of ubiquitin modifications present specific cellular and temporal distribution throughout the Giardia life cycle from trophozoites to cyst maturation. Ubiquitin signal was detected in the wall of mature cysts, and enzymes implicated in cyst wall biogenesis were identified as substrates for ubiquitination. Interestingly, inhibition of proteasome activity did not affect trophozoite replication and differentiation, while it caused a decrease in cyst viability, arguing for proteasome involvement in cyst wall maturation. Using a proteomics approach, we identified around 200 high-confidence ubiquitinated candidates that vary their ubiquitination status during differentiation. Our results indicate that ubiquitination is critical for several cellular processes in this primitive eukaryote.

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Regulation of Antigenic Variation inGiardia lamblia

Cited by 50 publications

References 151 publications

Giardia duodenalis: NEW INSIGHTS ON AN ANCIENT PARASITE

Giardia duodenalis: NEW INSIGHTS ON AN ANCIENT PARASITE

Antigenic Variation in Microbial Evasion of Immune Responses

Ubiquitination dynamics in the early‐branching eukaryote Giardia intestinalis

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