scholarly journals Two 20-Residue-Long Peptides Derived from Plasmodium vivax Merozoite Surface Protein 10 EGF-Like Domains Are Involved in Binding to Human Reticulocytes

2021 ◽  
Vol 22 (4) ◽  
pp. 1609
Author(s):  
Laura Alejandra Ricaurte-Contreras ◽  
Andrea Lovera ◽  
Darwin Andrés Moreno-Pérez ◽  
Michel David Bohórquez ◽  
Carlos Fernando Suárez ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Protein Interactions ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Cell Interaction ◽  
Target Cells ◽  
Initial Contact ◽  
T Cell Epitopes ◽  
Protein Protein Interactions ◽  
Protein Cell

Plasmodium parasites’ invasion of their target cells is a complex, multi-step process involving many protein-protein interactions. Little is known about how complex the interaction with target cells is in Plasmodium vivax and few surface molecules related to reticulocytes’ adhesion have been described to date. Natural selection, functional and structural analysis were carried out on the previously described vaccine candidate P. vivax merozoite surface protein 10 (PvMSP10) for evaluating its role during initial contact with target cells. It has been shown here that the recombinant carboxyl terminal region (rPvMSP10-C) bound to adult human reticulocytes but not to normocytes, as validated by two different protein-cell interaction assays. Particularly interesting was the fact that two 20-residue-long regions (388DKEECRCRANYMPDDSVDYF407 and 415KDCSKENGNCDVNAECSIDK434) were able to inhibit rPvMSP10-C binding to reticulocytes and rosette formation using enriched target cells. These peptides were derived from PvMSP10 epidermal growth factor (EGF)-like domains (precisely, from a well-defined electrostatic zone) and consisted of regions having the potential of being B- or T-cell epitopes. These findings provide evidence, for the first time, about the fragments governing PvMSP10 binding to its target cells, thus highlighting the importance of studying them for inclusion in a P. vivax antimalarial vaccine.

Engineering “Antimicrobial Peptides” and Other Peptides to Modulate Protein-Protein Interactions in Cancer

2020 ◽  
Vol 20 (32) ◽  
pp. 2970-2983
Author(s):  
Samuel J.S. Rubin ◽  
Nir Qvit
Keyword(s):  
Antimicrobial Peptides ◽  
Protein Interactions ◽  
Anticancer Agents ◽  
Cancer Therapeutics ◽  
Target Cells ◽  
Protein Protein Interactions ◽  
Peptide Backbone ◽  
Modified Peptides ◽  
Selective Death ◽  
Drug Leads

Antimicrobial peptides (AMPs) are a class of peptides found across a wide array of organisms that play key roles in host defense. AMPs induce selective death in target cells and orchestrate specific or nonspecific immune responses. Many AMPs exhibit native anticancer activity in addition to antibacterial activity, and others have been engineered as antineoplastic agents. We discuss the use of AMPs in the detection and treatment of cancer as well as mechanisms of AMP-induced cell death. We present key examples of cathelicidins and transferrins, which are major AMP families. Further, we discuss the critical roles of protein-protein interactions (PPIs) in cancer and how AMPs are well-suited to target PPIs based on their unique drug-like properties not exhibited by small molecules or antibodies. While peptides, including AMPs, can have limited stability and bioavailability, these issues can be overcome by peptide backbone modification or cyclization (e.g., stapling) and by the use of delivery systems such as cellpenetrating peptides (CPPs), respectively. We discuss approaches for optimizing drug properties of peptide and peptidomimetic leads (modified peptides), providing examples of promising techniques that may be applied to AMPs. These molecules represent an exciting resource as anticancer agents with unique therapeutic advantages that can target challenging mechanisms involving PPIs. Indeed, AMPs are suitable drug leads for further development of cancer therapeutics, and many studies to this end are underway.

scholarly journals PvMSP8 as a Novel Plasmodium vivax Malaria Sero-Marker for the Peruvian Amazon

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 282
Author(s):  
Elizabeth Villasis ◽  
Katherine Garro ◽  
Angel Rosas-Aguirre ◽  
Pamela Rodriguez ◽  
Jason Rosado ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Area Under The Curve ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Population Based ◽  
Peruvian Amazon ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Malaria Exposure ◽  
Plasmodium Vivax Malaria

The measurement of recent malaria exposure can support malaria control efforts. This study evaluated serological responses to an in-house Plasmodium vivax Merozoite Surface Protein 8 (PvMSP8) expressed in a Baculovirus system as sero-marker of recent exposure to P. vivax (Pv) in the Peruvian Amazon. In a first evaluation, IgGs against PvMSP8 and PvMSP10 proteins were measured by Luminex in a cohort of 422 Amazonian individuals with known history of Pv exposure (monthly data of infection status by qPCR and/or microscopy over five months). Both serological responses were able to discriminate between exposed and non-exposed individuals in a good manner, with slightly higher performance of anti-PvMSP10 IgGs (area under the curve AUC = 0.78 [95% CI = 0.72–0.83]) than anti-PvMSP8 IgGs (AUC = 0.72 [95% CI = 0.67–0.78]) (p = 0.01). In a second evaluation, the analysis by ELISA of 1251 plasma samples, collected during a population-based cross-sectional survey, confirmed the good performance of anti-PvMSP8 IgGs for discriminating between individuals with Pv infection at the time of survey and/or with antecedent of Pv in the past month (AUC = 0.79 [95% CI = 0.74–0.83]). Anti-PvMSP8 IgG antibodies can be considered as a good biomarker of recent Pv exposure in low-moderate transmission settings of the Peruvian Amazon.

scholarly journals TRIM22. A Multitasking Antiviral Factor

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1864
Author(s):  
Isabel Pagani ◽  
Guido Poli ◽  
Elisa Vicenzi
Keyword(s):  
Protein Interactions ◽  
Influenza A ◽  
Direct Interaction ◽  
Type I Interferons ◽  
Viral Gene ◽  
Target Cells ◽  
Type I ◽  
Protein Protein Interactions ◽  
Viral Genomes ◽  
Dna And Rna

Viral invasion of target cells triggers an immediate intracellular host defense system aimed at preventing further propagation of the virus. Viral genomes or early products of viral replication are sensed by a number of pattern recognition receptors, leading to the synthesis and production of type I interferons (IFNs) that, in turn, activate a cascade of IFN-stimulated genes (ISGs) with antiviral functions. Among these, several members of the tripartite motif (TRIM) family are antiviral executors. This article will focus, in particular, on TRIM22 as an example of a multitarget antiviral member of the TRIM family. The antiviral activities of TRIM22 against different DNA and RNA viruses, particularly human immunodeficiency virus type 1 (HIV-1) and influenza A virus (IAV), will be discussed. TRIM22 restriction of virus replication can involve either direct interaction of TRIM22 E3 ubiquitin ligase activity with viral proteins, or indirect protein–protein interactions resulting in control of viral gene transcription, but also epigenetic effects exerted at the chromatin level.

scholarly journals Mosaic organization and heterogeneity in frequency of allelic recombination of the Plasmodium vivax merozoite surface protein-1 locus

2002 ◽  
Vol 99 (25) ◽  
pp. 16348-16353 ◽  
Author(s):  
C. Putaporntip ◽  
S. Jongwutiwes ◽  
N. Sakihama ◽  
M. U. Ferreira ◽  
W.-G. Kho ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Merozoite Surface Protein 1

Plasmodium vivax merozoite surface protein PvMSP-3β is radically polymorphic through mutation and large insertions and deletions

2004 ◽  
Vol 4 (4) ◽  
pp. 309-319 ◽  
Author(s):  
Julian C. Rayner ◽  
Curtis S. Huber ◽  
Dmitry Feldman ◽  
Paul Ingravallo ◽  
Mary R. Galinski ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Insertions And Deletions

scholarly journals Application of 23 novel serological markers for identifying recent exposure to Plasmodium vivax parasites in an endemic population of western Thailand

2021 ◽  
Author(s):  
Sadudee Chotirat ◽  
Narimane Nekkab ◽  
Chalermpon Kumpitak ◽  
Jenni Hietanen ◽  
Michael T White ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Spatial Clustering ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Serological Markers ◽  
Igg Antibody ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Recent Exposure ◽  
Increased Risk

AbstractThailand is aiming for malaria elimination by the year 2030. However, the high proportion of asymptomatic infections and the presence of the hidden hypnozoite stage of Plasmodium vivax are impeding these efforts. We hypothesized that a validated surveillance tool utilizing serological markers of recent exposure to P. vivax infection could help to identify areas of ongoing transmission. The objective of this exploratory study was to assess the ability of P. vivax serological exposure markers to detect residual transmission ‘hot-spots’ in Western Thailand. Total IgG levels were measured against a panel of 23 candidate P. vivax serological exposure markers using a multiplexed bead-based assay. A total of 4255 plasma samples from a cross-sectional survey conducted in 2012 of endemic areas in the Kanchanaburi and Ratchaburi provinces were assayed. We compared IgG levels with multiple epidemiological factors that are associated with an increased risk of P. vivax infection in Thailand, including age, gender and spatial location, as well as Plasmodium infection status itself. IgG levels to all proteins were significantly higher in the presence of a P. vivax infection (n=144) (t test, p<0.0001). Overall seropositivity rates varied from 2.5% (PVX_097625, merozoite surface protein 8) to 16.8% (PVX_082670, merozoite surface protein 7), with 43% of individuals seropositive to at least 1 protein. Higher IgG levels were associated with older age (>18 years, p<0.05) and males (17/23 proteins, p<0.05), supporting the paradigm that men have a higher risk of infection than females in this setting. We used a Random Forests algorithm to predict which individuals had exposure to P. vivax parasites in the last 9-months, based on their IgG antibody levels to a panel of 8 previously validated P. vivax proteins. Spatial clustering was observed at the village and regional level, with a moderate correlation between PCR prevalence and sero-prevalence as predicted by the algorithm. Our data provides proof-of-concept for application of such surrogate markers as evidence of recent exposure in low transmission areas. These data can be used to better identify geographical areas with asymptomatic infection burdens that can be targeted in elimination campaigns.

scholarly journals Merozoite Surface Protein 1 of Plasmodium vivax Induces a Protective Response against Plasmodium cynomolgi Challenge in Rhesus Monkeys

2005 ◽  
Vol 73 (9) ◽  
pp. 5936-5944 ◽  
Author(s):  
Sheetij Dutta ◽  
Deep C. Kaushal ◽  
Lisa A. Ware ◽  
Sunil K. Puri ◽  
Nuzhat A. Kaushal ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Protective Efficacy ◽  
High Titer ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Control Group ◽  
Merozoite Surface Protein 1 ◽  
Significant Difference ◽  
Peak Parasitemia

ABSTRACT The 42-kDa fragment of the merozoite surface protein 1 (MSP-142) is a leading candidate for the development of a vaccine to control malaria. We previously reported a method for the production of Plasmodium vivax MSP-142 (PvMSP-142) as a soluble protein (S. Dutta, L. W. Ware, A. Barbosa, C. F. Ockenhouse, and D. E. Lanar, Infect. Immun. 69:5464-5470, 2001). We report here a process to manufacture the same PvMSP-142 protein but as an insoluble inclusion body-derived protein which was then refolded in vitro. We compared the immunogenicity and protective efficacy of the soluble and refolded forms of PvMSP-142 protein by using a heterologous but closely related P. cynomolgi-rhesus monkey challenge model. As comparative controls we also expressed, purified, and immunized rhesus with the soluble and refolded forms of the P. cynomolgi MSP-142 (PcMSP-142) proteins. All proteins induced equally high-titer, cross-reacting antibodies. Upon challenge with P. cynomolgi, none of the MSP-142-vaccinated groups demonstrated sterile protection or a delay in the prepatent period. However, following an initial rise in parasitemia, all MSP-1-vaccinated animals had significantly lower parasite burdens as indicated by lower cumulative parasitemia, lower peak parasitemia, lower secondary peak parasitemia, and lower average daily parasitemia compared to the adjuvant control group (P < 0.05). Except the soluble PcMSP-142 group, monkeys in all other groups had fewer numbers of days with parasitemia of >10,000 parasites mm−3. Interestingly, there was no significant difference in the level of partial protection observed in the homologous and heterologous groups in this challenge model. The soluble and refolded forms of PcMSP-142 and PvMSP-142 proteins also appeared to have a similar partially protective effect.

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