Comparison of two members of a multigene family coding for high-molecular mass rhoptry proteins of Plasmodium yoelii

Sinha, Katharine A.; Keen, Jane K.; Ogun, Solabomi A.; Holder, Anthony A.

doi:10.1016/0166-6851(95)02546-4

Cited by 25 publications

(16 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is known for the P. yoelii parasite that individual merozoites express a different Py235 gene (14). From analysis of the two Py235 genes for which sequence is available (e3 and e8 types), it appears that there are extensive differences at the protein level with approximately 25% sequence variation (18). In P. falciparum, the much more closely related proteins PfR2Ha and -Hb may be expressed differentially in individual merozoites.…”

Section: Discussionmentioning

confidence: 99%

Identification of Proteins from Plasmodium falciparum That Are Homologous to Reticulocyte Binding Proteins in Plasmodium vivax

et al. 2001

View full text Add to dashboard Cite

Plasmodium falciparum infections can be fatal, while P. vivax infections usually are not. A possible factor involved in the greater virulence of P. falciparum is that this parasite grows in red blood cells (RBCs) of all maturities whereas P. vivax is restricted to growth in reticulocytes, which represent only approximately 1% of total RBCs in the periphery. Two proteins, expressed at the apical end of the invasive merozoite stage from P. vivax, have been implicated in the targeting of reticulocytes for invasion by this parasite. A search of the P. falciparum genome databases has identified genes that are homologous to the P. vivax rbp-1 and -2 genes. Two of these genes are virtually identical over a large region of the 5 end but are highly divergent at the 3 end. They encode high-molecular-mass proteins of >300 kDa that are expressed in late schizonts and localized to the apical end of the merozoite. To test a potential role in merozoite invasion of RBCs, we analyzed the ability of these proteins to bind to mature RBCs and reticulocytes. No binding to mature RBCs or cell preparations enriched for reticulocytes was detected. We identified a parasite clone that lacks the gene for one of these proteins, showing that the gene is not required for normal in vitro growth. Antibodies to these proteins can inhibit merozoite invasion of RBCs.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification of Proteins from Plasmodium falciparum That Are Homologous to Reticulocyte Binding Proteins in Plasmodium vivax

et al. 2001

View full text Add to dashboard Cite

show abstract

“…2A) with the changes being detected within 2 days after the parasite was transferred to the new host, strongly suggesting that epigenetic factors rather then specific mutations play an important role in this upregulation and adaptation. An even more dramatic increase in the absolute amounts of total py235 was seen in YM with 100-1000-fold higher levels (P < 0.001) (Keen et al, 1994;Sinha et al, 1996) show differential pattern of expression of members of PY235 (indicated by asterisks) in YA and YM parasites. A. Quantitative real-time RT-PCR of total py235 levels transcribed in schizonts harvested from passages between mice and rats shows significant upregulation of py235 in rats (P < 0.004).…”

Section: Upregulation Of Py235 Transcription In Virulent and Adapted mentioning

confidence: 95%

“…Western blots were performed as previously described (Doolan, 2002), using either polyclonal S6 antibody (Fig. 1) (Keen et al, 1994;Sinha et al, 1996) or monoclonal 25.77 antibody (Fig. 2) (Freeman et al, 1980) on parasite lysates matched for number of schizonts loaded per lane.…”

Section: Western Blottingmentioning

confidence: 99%

“…Differences in the py235 repertoire and transcription profile observed between the YA and YM lines (Preiser and Jarra, 1998;Khan et al, 2001b), along with the challenge experiments is consistent with a role in virulence. There are at least 14 members of the approximately 8kb py235 gene (Keen et al, 1990a;Holder et al, 1991;Sinha et al, 1996;Khan et al, 2001b;Carlton et al, 2002;Preiser et al, 2002), distributed among multiple chromosomes ends of P. yoelii (Owen et al, 1999;Khan et al, 2001b) and members of this gene family are also found in Plasmodium berghei and Plasmodium chabaudi. At least one member of PY235 has been shown to bind to erythrocytes and in P. vivax and P. falciparum RBL proteins have also been shown to bind so far uncharacterized receptors on the erythrocyte (Rayner et al, 2001;Duraisingh et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Variable expression of the 235 kDa rhoptry protein of Plasmodium yoelii mediate host cell adaptation and immune evasion

Iyer

Amaladoss

Ganesan

et al. 2007

Molecular Microbiology

View full text Add to dashboard Cite

SummaryThe severity of infections caused by the malaria parasite Plasmodium is in part due to the rapid multiplication cycles in the blood of an infected individual. A fundamental step in this phenomenon is the invasion of selected erythrocytes of the host by the parasite. The py235 rhoptry protein multigene family of the rodent malaria parasite Plasmodium yoelii has been implicated in mediating host cell selection during erythrocyte invasion and virulence. Here we show using quantitative real-time polymerase chain reaction and Western blot analysis that variations in the amounts of py235 may be a mechanism that the parasite uses to define its host cell repertoire. High levels of py235 expression leads to a wider range of erythrocytes invaded and therefore increased virulence. In contrast, to evade PY235-specific immunity, the parasite downregulates py235 thereby decreasing the host cell repertoire and virulence. These results demonstrate a new mechanism where variations in the amounts of parasite ligand define the parasite host cell repertoire and enable it to evade host immunity.

show abstract

“…When these sequences were compared to the known P235 protein sequences (15,25,31,45) and P. yoelii genome sequence data [http://www.plasmodb.org], no region of similarity was identified.…”

Section: Resultsmentioning

confidence: 99%

Passive Immunization with a Multicomponent Vaccine against Conserved Domains of Apical Membrane Antigen 1 and 235-Kilodalton Rhoptry Proteins Protects Mice againstPlasmodium yoeliiBlood-Stage Challenge Infection

Narum

Ogun²,

Batchelor

et al. 2006

Infect Immun

Self Cite

View full text Add to dashboard Cite

During malaria parasite invasion of red blood cells, merozoite proteins bind receptors on the surface of the erythrocyte. Two candidate Plasmodium yoelii adhesion proteins are apical membrane antigen 1 (AMA1) and the 235-kDa rhoptry proteins (P235). Previously, we have demonstrated that passive immunization with monoclonal antibodies (MAbs) 45B1 and 25.77 against AMA1 and P235, respectively, protects against a lethal challenge infection with P. yoelii YM. We show that MAb 45B1 recognizes an epitope located on a conserved surface of PyAMA1, as determined by phage display and analysis of the three-dimensional structure of AMA1, in a region similar to that bound by the P. falciparum AMA1-specific inhibitory antibody 4G2. The epitope recognized by 25.77 could not be assigned. We report here that MAbs 45B1 and 25.77 also protect against challenge with the nonlethal parasite line 17X, in which PyAMA1 has a significantly different amino acid sequence from that in YM. When administered together, the two MAbs acted at least additively in providing protection against challenge with the virulent YM parasite. These results support the concept of developing a multicomponent blood-stage vaccine and the inclusion of polymorphic targets such as AMA1, which these results suggest contain conserved domains recognized by inhibitory antibodies.

show abstract

Comparison of two members of a multigene family coding for high-molecular mass rhoptry proteins of Plasmodium yoelii

Cited by 25 publications

References 11 publications

Identification of Proteins from Plasmodium falciparum That Are Homologous to Reticulocyte Binding Proteins in Plasmodium vivax

Identification of Proteins from Plasmodium falciparum That Are Homologous to Reticulocyte Binding Proteins in Plasmodium vivax

Variable expression of the 235 kDa rhoptry protein of Plasmodium yoelii mediate host cell adaptation and immune evasion

Passive Immunization with a Multicomponent Vaccine against Conserved Domains of Apical Membrane Antigen 1 and 235-Kilodalton Rhoptry Proteins Protects Mice againstPlasmodium yoeliiBlood-Stage Challenge Infection

Contact Info

Product

Resources

About