Cloning and analysis of the RESA-2 gene: a DNA homologue of the ring-infected erythrocyte surface antigen gene of Plasmodium falciparum

Cappai, Roberto; Dc, Kaslow; Mg, Peterson; Af, Cowman; Rf, Anders; Dj, Kemp

doi:10.1016/0166-6851(92)90113-x

Cited by 20 publications

(16 citation statements)

References 30 publications

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“…Three genes-RESA-2 (PF11_0512), a putative long-chain fatty-acid ligase (PFC0050c), and a stevor (PFD0065w)-were overexpressed in all in vivo samples (table 2). RESA-2 was not detected in any 3D7 stage or in previous in vitro studies of laboratory-adapted strains [18,19]. However, RESA-2 transcript was detected in freshly obtained samples from infected patients in French Guiana [20].…”

Section: Resultscontrasting

confidence: 50%

In Vivo Transcriptome ofPlasmodium falciparumReveals Overexpression of Transcripts That Encode Surface Proteins

Daily¹,

Roch²,

Sarr³

et al. 2005

J INFECT DIS

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Infections with the human parasite Plasmodium falciparum continue to present a great challenge to global health. Fundamental questions regarding the molecular basis of virulence and immune evasion in P. falciparum have been only partially answered. Because of the parasite's intracellular location and complex life cycle, standard genetic approaches to the study of the pathogenesis of malaria have been limited. The present study presents a novel approach to the identification of the biological processes involved in host-pathogen interactions, one that is based on the analysis of in vivo P. falciparum transcripts. We demonstrate that a sufficient quantity of P. falciparum RNA transcripts can be derived from a small blood sample from infected patients for whole-genome microarray analysis. Overall, excellent correlation was observed between the transcriptomes derived from in vivo samples and in vitro samples with ring-stage P. falciparum 3D7 reference strain. However, gene families that encode surface proteins are overexpressed in vivo. Moreover, this analysis has identified a new family of hypothetical genes that may encode surface variant antigens. Comparative studies of the transcriptomes derived from in vivo samples and in vitro 3D7 samples may identify important strategies used by the pathogen for survival in the human host and highlight, for vaccine development, new candidate antigens that were not previously identified through the use of in vitro cultures.

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Section: Resultscontrasting

confidence: 50%

In Vivo Transcriptome ofPlasmodium falciparumReveals Overexpression of Transcripts That Encode Surface Proteins

Daily¹,

Roch²,

Sarr³

et al. 2005

J INFECT DIS

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“…The resa2 gene (accession number M91672) was first reported as a pseudogene based on the presence of an internal stop codon [16]. Interestingly, SNP affecting the third base of this internal stop codon is described in PlasmodB with the replacement of the internal stop codon by a Glutamine codon in some laboratory parasite strains (e.g.…”

Section: Introductionmentioning

confidence: 99%

“…This T1526C mutation may restore a unique open reading frame and thus the ability to give rise to a full-length protein. Large differences in resa2 gene transcription in vitro have been reported [16,17] and increased transcription of this gene was observed after parasite exposure at 41°C [3]. In vivo resa2 behave as a transcribed pseudogene [18] and analysis of gene expression profiles in malaria patients has consistently outlined resa2 expression and up-regulation in vivo [18-20].…”

Section: Introductionmentioning

confidence: 99%

Possible association of the Plasmodium falciparum T1526C resa2 gene mutation with severe malaria

Durand

Migot-Nabias

Andriantsoanirina

et al. 2012

Malar J

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BackgroundPlasmodium falciparum exports proteins that remodel the erythrocyte membrane. One such protein, called Pf155/RESA (RESA1) contributes to parasite fitness, optimizing parasite survival during febrile episodes. Resa1 gene is a member of a small family comprising three highly related genes. Preliminary evidence led to a search for clues indicating the involvement of RESA2 protein in the pathophysiology of malaria. In the present study, cDNA sequence of resa2 gene was obtained from two different strains. The proportion of P. falciparum isolates having a non-stop T1526C mutation in resa2 gene was evaluated and the association of this genotype with severity of malaria was investigated.MethodsResa2 cDNAs of two different strains (a patient isolate and K1 culture adapted strain) was obtained by RT-PCR and DNA sequencing was performed to confirm its gene structure. The proportion of isolates having a T1526C mutation was evaluated using a PCR-RFLP methodology on groups of severe malaria and uncomplicated patients recruited in 1991–1994 in Senegal and in 2009 in Benin.ResultsA unique ORF with an internal translation stop was found in the patient isolate (Genbank access number : JN183870), while the K1 strain harboured the T1526C mutation (Genbank access number : JN183869) which affects the internal stop codon and restores a full length coding sequence. About 14% of isolates obtained from Senegal and Benin harboured mutant T1526C parasites. Some isolates had both wild and mutant resa alleles. The analysis excluding those mixed isolates showed that the resa2 T1526C mutation was found more frequently in severe malaria cases than in uncomplicated cases (p = 0.008). The association of the presence of the mutant allele and parasitaemia >4% was shown in multivariate analysis (p = 0.03) in the group of Beninese children.ConclusionsAll T1526C mutant parasites theoretically have the ability to give rise to a full-length RESA2 protein. This study raises the hypothesis that the RESA2 protein could favour high-density infections. Other studies in various geographic settings and probably including more patients are now required to replicate these results and to answer the questions raised by these results.

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“…Pseudogenes in P. falciparum have been described in the large PfEMP1 family, the family of erythrocyte binding proteins (EBA) and for the ring-infected erythrocyte membrane antigen RESA. RESA-2 is a homologue of the ring-infected erythrocyte surface antigen RESA from P. falciparum, which contains a stop codon in the reading frame (Cappai et al 1992). It was shown that RESA-2 was transcribed and that the mRNA was correctly spliced (Vazeux et al 1993).…”

Section: Discussionmentioning

confidence: 98%

Genes coding for tryptophan-rich proteins are transcribed throughout the asexual cycle of Plasmodium falciparum

Ntumngia¹,

Bahamontes-Rosa²,

Kun³

2005

Parasitol Res

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Multigene families are a common feature in Plasmodia spp. and constitute a substantial content of the parasite genome. Here, we analyse the structural organisation and sequence diversity of two further members of the Trp-rich multigene family of P. falciparum. The complete DNA sequence of both genes was determined from a series of laboratory adapted and field isolates. Based on the amino acid sequences, we have termed them tryptophan-rich antigen-3 (TrpA-3) and lysine-tryptophan-rich antigen (LysTrpA). Analysis of the genes using reverse transcriptase-polymerase chain reaction (RT-PCR), showed that both genes are transcribed and that introns are spliced out at predicted positions. Gene expression profiles obtained from microarray analysis indicate that both genes are expressed in the mid-stages of the asexual cycle. In-frame stop codons were detected which interrupted the reading frame of LysTrpA. Whereas the number of the Trp-rich proteins is rather low in P. falciparum, P. chabaudi, P. berghei and P. yoelii, this family seems to have 15 or more members in P. knowlesi and P. vivax.

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Cloning and analysis of the RESA-2 gene: a DNA homologue of the ring-infected erythrocyte surface antigen gene of Plasmodium falciparum

Cited by 20 publications

References 30 publications

In Vivo Transcriptome ofPlasmodium falciparumReveals Overexpression of Transcripts That Encode Surface Proteins

In Vivo Transcriptome ofPlasmodium falciparumReveals Overexpression of Transcripts That Encode Surface Proteins

Possible association of the Plasmodium falciparum T1526C resa2 gene mutation with severe malaria

Genes coding for tryptophan-rich proteins are transcribed throughout the asexual cycle of Plasmodium falciparum

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