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  1. Article ; Online: Proteomics approaches for the identification of protease substrates during virus infection.

    Martiáñez-Vendrell, Xavier / Kikkert, Marjolein

    Advances in virus research

    2021  Volume 109, Page(s) 135–161

    Abstract: Proteases precisely and irreversibly catalyze the hydrolysis of peptide bonds, regulating the fate, localization, and activity of many proteins. Consequently, proteolytic activity plays an important role in fundamental cellular processes such as ... ...

    Abstract Proteases precisely and irreversibly catalyze the hydrolysis of peptide bonds, regulating the fate, localization, and activity of many proteins. Consequently, proteolytic activity plays an important role in fundamental cellular processes such as differentiation and migration, immunological and inflammatory reactions, apoptosis and survival. During virus infection, host proteases are involved in several processes, from cell entry to initiation, progression and resolution of inflammation. On the other hand, many viruses encode their own highly specific proteases, responsible for the proteolytic processing of viral proteins, but, at the same time, to cleave host proteins to corrupt antiviral host responses and adjust protein activity to favor viral replication. Traditionally, protease substrate identification has been addressed by means of hypothesis-driven approaches, but recent advances in proteomics have made a toolkit available to uncover the extensive repertoire of host proteins cleaved during infection, either by viral or host proteases. Here, we review the currently available proteomics-based methods that can and have contributed to the systematic and unbiased identification of new protease substrates in the context of virus-host interactions. The role of specific proteases during the course of virus infections will also be highlighted.
    MeSH term(s) Animals ; Books ; Host Microbial Interactions ; Humans ; Mice ; Peptide Hydrolases/metabolism ; Proteolysis ; Proteomics/methods ; Viral Proteins/metabolism ; Virus Diseases/physiopathology ; Virus Replication
    Chemical Substances Viral Proteins ; Peptide Hydrolases (EC 3.4.-)
    Language English
    Publishing date 2021-04-20
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 195-8
    ISSN 1557-8399 ; 0065-3527
    ISSN (online) 1557-8399
    ISSN 0065-3527
    DOI 10.1016/bs.aivir.2021.03.003
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Factors Affecting the Performance of HRP2-Based Malaria Rapid Diagnostic Tests.

    Martiáñez-Vendrell, Xavier / Skjefte, Malia / Sikka, Ruhi / Gupta, Himanshu

    Tropical medicine and infectious disease

    2022  Volume 7, Issue 10

    Abstract: The recent COVID-19 pandemic has profoundly impacted global malaria elimination programs, resulting in a sharp increase in malaria morbidity and mortality. To reduce this impact, unmet needs in malaria diagnostics must be addressed while resuming malaria ...

    Abstract The recent COVID-19 pandemic has profoundly impacted global malaria elimination programs, resulting in a sharp increase in malaria morbidity and mortality. To reduce this impact, unmet needs in malaria diagnostics must be addressed while resuming malaria elimination activities. Rapid diagnostic tests (RDTs), the unsung hero in malaria diagnosis, work to eliminate the prevalence of
    Language English
    Publishing date 2022-09-25
    Publishing country Switzerland
    Document type Journal Article ; Review
    ISSN 2414-6366
    ISSN (online) 2414-6366
    DOI 10.3390/tropicalmed7100265
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Plasma MicroRNA Profiling of Plasmodium falciparum Biomass and Association with Severity of Malaria Disease.

    Gupta, Himanshu / Rubio, Mercedes / Sitoe, Antonio / Varo, Rosauro / Cisteró, Pau / Madrid, Lola / Cuamba, Inocencia / Jimenez, Alfons / Martiáñez-Vendrell, Xavier / Barrios, Diana / Pantano, Lorena / Brimacombe, Allison / Bustamante, Mariona / Bassat, Quique / Mayor, Alfredo

    Emerging infectious diseases

    2021  Volume 27, Issue 2, Page(s) 430–442

    Abstract: Severe malaria (SM) is a major public health problem in malaria-endemic countries. Sequestration of Plasmodium falciparum-infected erythrocytes in vital organs and the associated inflammation leads to organ dysfunction. MicroRNAs (miRNAs), which are ... ...

    Abstract Severe malaria (SM) is a major public health problem in malaria-endemic countries. Sequestration of Plasmodium falciparum-infected erythrocytes in vital organs and the associated inflammation leads to organ dysfunction. MicroRNAs (miRNAs), which are rapidly released from damaged tissues into the host fluids, constitute a promising biomarker for the prognosis of SM. We applied next-generation sequencing to evaluate the differential expression of miRNAs in SM and in uncomplicated malaria (UM) in children in Mozambique. Six miRNAs were associated with in vitro P. falciparum cytoadhesion, severity in children, and P. falciparum biomass. Relative expression of hsa-miR-4497 quantified by TaqMan-quantitative reverse transcription PCR was higher in plasma of children with SM than those with UM (p<0.048) and again correlated with P. falciparum biomass (p = 0.033). These findings suggest that different physiopathological processes in SM and UM lead to differential expression of miRNAs and suggest a pathway for assessing their prognostic value malaria.
    MeSH term(s) Biomass ; Child ; Humans ; Malaria ; Malaria, Falciparum ; MicroRNAs/genetics ; Mozambique ; Plasmodium falciparum/genetics
    Chemical Substances MicroRNAs
    Language English
    Publishing date 2021-01-26
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1380686-5
    ISSN 1080-6059 ; 1080-6040
    ISSN (online) 1080-6059
    ISSN 1080-6040
    DOI 10.3201/eid2702.191795
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Quantification of malaria antigens PfHRP2 and pLDH by quantitative suspension array technology in whole blood, dried blood spot and plasma.

    Martiáñez-Vendrell, Xavier / Jiménez, Alfons / Vásquez, Ana / Campillo, Ana / Incardona, Sandra / González, Raquel / Gamboa, Dionicia / Torres, Katherine / Oyibo, Wellington / Faye, Babacar / Macete, Eusebio / Menéndez, Clara / Ding, Xavier C / Mayor, Alfredo

    Malaria journal

    2020  Volume 19, Issue 1, Page(s) 12

    Abstract: Background: Malaria diagnostics by rapid diagnostic test (RDT) relies primarily on the qualitative detection of Plasmodium falciparum histidine-rich protein 2 (PfHRP2) and Plasmodium spp lactate dehydrogenase (pLDH). As novel RDTs with increased ... ...

    Abstract Background: Malaria diagnostics by rapid diagnostic test (RDT) relies primarily on the qualitative detection of Plasmodium falciparum histidine-rich protein 2 (PfHRP2) and Plasmodium spp lactate dehydrogenase (pLDH). As novel RDTs with increased sensitivity are being developed and implemented as point of care diagnostics, highly sensitive laboratory-based assays are needed for evaluating RDT performance. Here, a quantitative suspension array technology (qSAT) was developed, validated and applied for the simultaneous detection of PfHRP2 and pLDH in a variety of biological samples (whole blood, plasma and dried blood spots) from individuals living in different endemic countries.
    Results: The qSAT was specific for the target antigens, with analytical ranges of 6.8 to 762.8 pg/ml for PfHRP2 and 78.1 to 17076.6 pg/ml for P. falciparum LDH (Pf-LDH). The assay detected Plasmodium vivax LDH (Pv-LDH) at a lower sensitivity than Pf-LDH (analytical range of 1093.20 to 187288.5 pg/ml). Both PfHRP2 and pLDH levels determined using the qSAT showed to positively correlate with parasite densities determined by quantitative PCR (Spearman r = 0.59 and 0.75, respectively) as well as microscopy (Spearman r = 0.40 and 0.75, respectively), suggesting the assay to be a good predictor of parasite density.
    Conclusion: This immunoassay can be used as a reference test for the detection and quantification of PfHRP2 and pLDH, and could serve for external validation of RDT performance, to determine antigen persistence after parasite clearance, as well as a complementary tool to assess malaria burden in endemic settings.
    MeSH term(s) Adolescent ; Adult ; Africa ; Animals ; Antigens, Protozoan/blood ; Biotin ; Calibration ; Child ; Cross-Sectional Studies ; Female ; High-Throughput Nucleotide Sequencing/methods ; Humans ; L-Lactate Dehydrogenase/blood ; Malaria, Falciparum/blood ; Malaria, Falciparum/diagnosis ; Malaria, Vivax/blood ; Malaria, Vivax/diagnosis ; Mice ; Microspheres ; Parasitemia/blood ; Parasitemia/diagnosis ; Pregnancy ; Protozoan Proteins/blood ; Real-Time Polymerase Chain Reaction ; South America ; Spain ; Young Adult
    Chemical Substances Antigens, Protozoan ; HRP-2 antigen, Plasmodium falciparum ; Protozoan Proteins ; Biotin (6SO6U10H04) ; L-Lactate Dehydrogenase (EC 1.1.1.27)
    Language English
    Publishing date 2020-01-09
    Publishing country England
    Document type Journal Article
    ISSN 1475-2875
    ISSN (online) 1475-2875
    DOI 10.1186/s12936-019-3083-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Prevalence and clinical impact of malaria infections detected with a highly sensitive HRP2 rapid diagnostic test in Beninese pregnant women.

    Briand, Valérie / Cottrell, Gilles / Tuike Ndam, Nicaise / Martiáñez-Vendrell, Xavier / Vianou, Bertin / Mama, Atika / Kouwaye, Bienvenue / Houzé, Sandrine / Bailly, Justine / Gbaguidi, Erasme / Sossou, Darius / Massougbodji, Achille / Accrombessi, Manfred / Mayor, Alfredo / Ding, Xavier C / Fievet, Nadine

    Malaria journal

    2020  Volume 19, Issue 1, Page(s) 188

    Abstract: Background: While sub-microscopic malarial infections are frequent and potentially deleterious during pregnancy, routine molecular detection is still not feasible. This study aimed to assess the performance of a Histidine Rich Protein 2 (HRP2)-based ... ...

    Abstract Background: While sub-microscopic malarial infections are frequent and potentially deleterious during pregnancy, routine molecular detection is still not feasible. This study aimed to assess the performance of a Histidine Rich Protein 2 (HRP2)-based ultrasensitive rapid diagnostic test (uRDT, Alere Malaria Ag Pf) for the detection of infections of low parasite density in pregnant women.
    Methods: This was a retrospective study based on samples collected in Benin from 2014 to 2017. A total of 942 whole blood samples collected in 327 women in the 1st and 3rd trimesters and at delivery were tested by uRDT, conventional RDT (cRDT, SD BIOLINE Malaria Ag Pf), microscopy, quantitative polymerase chain-reaction (qPCR) and Luminex-based suspension array technology targeting P. falciparum HRP2. The performance of each RDT was evaluated using qPCR as reference standard. The association between infections detected by uRDT, but not by cRDT, with poor maternal and birth outcomes was assessed using multivariate regression models.
    Results: The overall positivity rate detected by cRDT, uRDT, and qPCR was 11.6% (109/942), 16.2% (153/942) and 18.3% (172/942), respectively. Out of 172 qPCR-positive samples, 68 were uRDT-negative. uRDT had a significantly better sensitivity (60.5% [52.7-67.8]) than cRDT (44.2% [36.6-51.9]) and a marginally decreased specificity (93.6% [91.7-95.3] versus 95.7% [94.0-97.0]). The gain in sensitivity was particularly high (33%) and statistically significant in the 1st trimester. Only 28 (41%) out of the 68 samples which were qPCR-positive, but uRDT-negative had detectable but very low levels of HRP2 (191 ng/mL). Infections that were detected by uRDT but not by cRDT were associated with a 3.4-times (95%CI 1.29-9.19) increased risk of anaemia during pregnancy.
    Conclusions: This study demonstrates the higher performance of uRDT, as compared to cRDTs, to detect low parasite density P. falciparum infections during pregnancy, particularly in the 1st trimester. uRDT allowed the detection of infections associated with maternal anaemia.
    MeSH term(s) Adult ; Antigens, Protozoan/analysis ; Diagnostic Tests, Routine/statistics & numerical data ; Female ; Humans ; Malaria, Falciparum/epidemiology ; Malaria, Falciparum/parasitology ; Plasmodium falciparum/isolation & purification ; Pregnancy ; Prevalence ; Protozoan Proteins/analysis ; Retrospective Studies ; Sensitivity and Specificity ; Young Adult
    Chemical Substances Antigens, Protozoan ; HRP-2 antigen, Plasmodium falciparum ; Protozoan Proteins
    Language English
    Publishing date 2020-05-24
    Publishing country England
    Document type Journal Article
    ISSN 1475-2875
    ISSN (online) 1475-2875
    DOI 10.1186/s12936-020-03261-1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Correction to: Prevalence and clinical impact of malaria infections detected with a highly sensitive HRP2 rapid diagnostic test in Beninese pregnant women.

    Briand, Valérie / Cottrell, Gilles / Tuikue Ndam, Nicaise / Martiáñez-Vendrell, Xavier / Vianou, Bertin / Mama, Atika / Kouwaye, Bienvenue / Houzé, Sandrine / Bailly, Justine / Gbaguidi, Erasme / Sossou, Darius / Massougbodji, Achille / Accrombessi, Manfred / Mayor, Alfredo / Ding, Xavier C / Fievet, Nadine

    Malaria journal

    2020  Volume 19, Issue 1, Page(s) 328

    Abstract: An amendment to this paper has been published and can be accessed via the original article. ...

    Abstract An amendment to this paper has been published and can be accessed via the original article.
    Language English
    Publishing date 2020-09-07
    Publishing country England
    Document type Published Erratum
    ISSN 1475-2875
    ISSN (online) 1475-2875
    DOI 10.1186/s12936-020-03400-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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