المؤلفون: Luca Ferretti, Eva Pérez-Martín, Fuquan Zhang, François Maree, Lin-Mari de Klerk-Lorist, Louis van Schalkwykc, Nicholas D Juleff, Bryan Charleston, Paolo Ribeca

المصدر: PLoS Pathogens, Vol 16, Iss 10, p e1009050 (2020)

مصطلحات موضوعية: Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5

الوصف: [This corrects the article DOI: 10.1371/journal.ppat.1008235.].

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1553-7366Test; https://doaj.org/toc/1553-7374Test

الوصول الحر: https://doaj.org/article/b0b350e896694344821d55dd2695be38Test

المؤلفون: Luca Ferretti, Eva Pérez-Martín, Fuquan Zhang, François Maree, Lin-Mari de Klerk-Lorist, Louis van Schalkwykc, Nicholas D Juleff, Bryan Charleston, Paolo Ribeca

المصدر: PLoS Pathogens, Vol 16, Iss 1, p e1008235 (2020)

مصطلحات موضوعية: Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5

الوصف: Although recombination is known to occur in foot-and-mouth disease virus (FMDV), it is considered only a minor determinant of virus sequence diversity. Analysis at phylogenetic scales shows inter-serotypic recombination events are rare, whereby recombination occurs almost exclusively in non-structural proteins. In this study we have estimated recombination rates within a natural host in an experimental setting. African buffaloes were inoculated with a SAT-1 FMDV strain containing two major viral sub-populations differing in their capsid sequence. This population structure enabled the detection of extensive within-host recombination in the genomic region coding for structural proteins and allowed recombination rates between the two sub-populations to be estimated. Quite surprisingly, the effective recombination rate in VP1 during the acute infection phase turns out to be about 0.1 per base per year, i.e. comparable to the mutation/substitution rate. Using a high-resolution map of effective within-host recombination in the capsid-coding region, we identified a linkage disequilibrium pattern in VP1 that is consistent with a mosaic structure with two main genetic blocks. Positive epistatic interactions between co-evolved variants appear to be present both within and between blocks. These interactions are due to intra-host selection both at the RNA and protein level. Overall our findings show that during FMDV co-infections by closely related strains, capsid-coding genes recombine within the host at a much higher rate than expected, despite the presence of strong constraints dictated by the capsid structure. Although these intra-host results are not immediately translatable to a phylogenetic setting, recombination and epistasis must play a major and so far underappreciated role in the molecular evolution of the virus at all scales.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1553-7366Test; https://doaj.org/toc/1553-7374Test

الوصول الحر: https://doaj.org/article/6e3100fb11844302b10a953fdafc4e5eTest

المؤلفون: Luca Ferretti, Antonello Di Nardo, Benjamin Singer, Lidia Lasecka-Dykes, Grace Logan, Caroline F. Wright, Eva Pérez-Martín, Donald P. King, Tobias J. Tuthill, Paolo Ribeca

المصدر: Viruses, Vol 10, Iss 5, p 221 (2018)

مصطلحات موضوعية: recombination, quasi-species, intra-host diversity, linkage disequilibrium, Microbiology, QR1-502

الوصف: Recombination is one of the determinants of genetic diversity in the foot-and-mouth disease virus (FMDV). FMDV sequences have a mosaic structure caused by extensive intra- and inter-serotype recombination, with the exception of the capsid-encoding region. While these genome-wide patterns of broad-scale recombination are well studied, not much is known about the patterns of recombination that may exist within infected hosts. In addition, detection of recombination among viruses evolving at the within-host level is challenging due to the similarity of the sequences and the limitations in differentiating recombination from point mutations. Here, we present the first analysis of recombination events between closely related FMDV sequences occurring within buffalo hosts. The detection of these events was made possible by the occurrence of co-infection of two viral swarms with about 1% nucleotide divergence. We found more than 15 recombination events, unequally distributed across eight samples from different animals. The distribution of these events along the FMDV genome was neither uniform nor related to the phylogenetic distribution of recombination breakpoints, suggesting a mismatch between within-host evolutionary pressures and long-term selection for infectivity and transmissibility.

وصف الملف: electronic resource

العلاقة: http://www.mdpi.com/1999-4915/10/5/221Test; https://doaj.org/toc/1999-4915Test

الوصول الحر: https://doaj.org/article/887f76236d5147179bf3a15c2d5743caTest

المؤلفون: Jordi M Argilaguet, Eva Pérez-Martín, Miquel Nofrarías, Carmina Gallardo, Francesc Accensi, Anna Lacasta, Mercedes Mora, Maria Ballester, Ivan Galindo-Cardiel, Sergio López-Soria, José M Escribano, Pedro A Reche, Fernando Rodríguez

المصدر: PLoS ONE, Vol 7, Iss 9, p e40942 (2012)

مصطلحات موضوعية: Medicine, Science

الوصف: The lack of available vaccines against African swine fever virus (ASFV) means that the evaluation of new immunization strategies is required. Here we show that fusion of the extracellular domain of the ASFV Hemagglutinin (sHA) to p54 and p30, two immunodominant structural viral antigens, exponentially improved both the humoral and the cellular responses induced in pigs after DNA immunization. However, immunization with the resulting plasmid (pCMV-sHAPQ) did not confer protection against lethal challenge with the virulent E75 ASFV-strain. Due to the fact that CD8(+) T-cell responses are emerging as key components for ASFV protection, we designed a new plasmid construct, pCMV-UbsHAPQ, encoding the three viral determinants above mentioned (sHA, p54 and p30) fused to ubiquitin, aiming to improve Class I antigen presentation and to enhance the CTL responses induced. As expected, immunization with pCMV-UbsHAPQ induced specific T-cell responses in the absence of antibodies and, more important, protected a proportion of immunized-pigs from lethal challenge with ASFV. In contrast with control pigs, survivor animals showed a peak of CD8(+) T-cells at day 3 post-infection, coinciding with the absence of viremia at this time point. Finally, an in silico prediction of CTL peptides has allowed the identification of two SLA I-restricted 9-mer peptides within the hemagglutinin of the virus, capable of in vitro stimulating the specific secretion of IFNγ when using PBMCs from survivor pigs. Our results confirm the relevance of T-cell responses in protection against ASF and open new expectations for the future development of more efficient recombinant vaccines against this disease.

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC3458849?pdf=renderTest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/ff9f0a0ee55543a6a8e7739ce0242728Test

المؤلفون: Felicitat Todolí, Alhelí Rodríguez-Cortés, María Del Carmen Núñez, Márcia D Laurenti, Silvia Gómez-Sebastián, Fernando Rodríguez, Eva Pérez-Martín, José M Escribano, Jordi Alberola

المصدر: PLoS ONE, Vol 7, Iss 12, p e51181 (2012)

مصطلحات موضوعية: Medicine, Science

الوصف: Parasitic diseases plague billions of people among the poorest, killing millions annually, and causing additional millions of disability-adjusted life years lost. Leishmaniases affect more than 12 million people, with over 350 million people at risk. There is an urgent need for efficacious and cheap vaccines and treatments against visceral leishmaniasis (VL), its most severe form. Several vaccination strategies have been proposed but to date no head-to-head comparison was undertaken to assess which is the best in a clinical model of the disease. We simultaneously assayed three vaccination strategies against VL in the hamster model, using KMPII, TRYP, LACK, and PAPLE22 vaccine candidate antigens. Four groups of hamsters were immunized using the following approaches: 1) raw extracts of baculovirus-infected Trichoplusia ni larvae expressing individually one of the four recombinant proteins (PROT); 2) naked pVAX1 plasmids carrying the four genes individually (DNA); 3) a heterologous prime-boost (HPB) strategy involving DNA followed by PROT (DNA-PROT); and 4) a Control including empty pVAX1 plasmid followed by raw extract of wild-type baculovirus-infected T. ni larvae. Hamsters were challenged with L. infantum promastigotes and maintained for 20 weeks. While PROT vaccine was not protective, DNA vaccination achieved protection in spleen. Only DNA-PROT vaccination induced significant NO production by macrophages, accompanied by a significant parasitological protection in spleen and blood. Thus, the DNA-PROT strategy elicits strong immune responses and high parasitological protection in the clinical model of VL, better than its corresponding naked DNA or protein versions. Furthermore, we show that naked DNA coupled with raw recombinant proteins produced in insect larvae biofactories -the cheapest way of producing DNA-PROT vaccines- is a practical and cost-effective way for potential "off the shelf" supplying vaccines at very low prices for the protection against leishmaniases, and possibly against other parasitic diseases affecting the poorest of the poor.

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC3517401?pdf=renderTest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/f765df0972784e4cbb8167c1b8d1d0dfTest

المؤلفون: Lucy Gordon, Neil Mabbott, Joanna Wells, Liudmila Kulik, Nick Juleff, Bryan Charleston, Eva Perez-Martin

المصدر: PLoS Pathogens, Vol 18, Iss 5, p e1009942 (2022)

مصطلحات موضوعية: Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5

الوصف: Previous studies have shown after the resolution of acute infection and viraemia, foot-and-mouth disease virus (FMDV) capsid proteins and/or genome are localised in the light zone of germinal centres of lymphoid tissue in cattle and African buffalo. The pattern of staining for FMDV proteins was consistent with the virus binding to follicular dendritic cells (FDCs). We have now demonstrated a similar pattern of FMDV protein staining in mouse spleens after acute infection and showed FMDV proteins are colocalised with FDCs. Blocking antigen binding to complement receptor type 2 and 1 (CR2/CR1) prior to infection with FMDV significantly reduced the detection of viral proteins on FDCs and FMDV genomic RNA in spleen samples. Blocking the receptors prior to infection also significantly reduced neutralising antibody titres, through significant reduction in their avidity to the FMDV capsid. Therefore, the binding of FMDV to FDCs and sustained induction of neutralising antibody responses are dependent on FMDV binding to CR2/CR1 in mice.

العلاقة: https://doi.org/10.1371/journal.ppat.1009942Test; https://doaj.org/toc/1553-7366Test; https://doaj.org/toc/1553-7374Test; https://doaj.org/article/0491e520f37f4b9689b8552a64d5adcfTest

الإتاحة: https://doi.org/10.1371/journal.ppat.1009942Test
https://doaj.org/article/0491e520f37f4b9689b8552a64d5adcfTest

المؤلفون: Eva Perez-Martin, Brianna Beechler, Fuquan Zhang, Katherine Scott, Lin-Mari de Klerk-Lorist, Georgina Limon, Brian Dugovich, Simon Gubbins, Arista Botha, Robyn Hetem, Louis van Schalkwyk, Nicholas Juleff, Francois F. Maree, Anna Jolles, Bryan Charleston

المصدر: Veterinary Research, Vol 53, Iss 1, Pp 1-14 (2022)

مصطلحات موضوعية: SAT, FMDV, host-viral interaction, innate immune response, acute phase proteins, fever, Veterinary medicine, SF600-1100

الوصف: Foot-and-mouth disease (FMD) is one of the most important livestock diseases restricting international trade. While African buffalo (Syncerus caffer) act as the main wildlife reservoir, viral and immune response dynamics during FMD virus acute infection have not been described before in this species. We used experimental needle inoculation and contact infections with three Southern African Territories serotypes to assess clinical, virological and immunological dynamics for thirty days post infection. Clinical FMD in the needle inoculated buffalo was mild and characterised by pyrexia. Despite the absence of generalised vesicles, all contact animals were readily infected with their respective serotypes within the first two to nine days after being mixed with needle challenged buffalo. Irrespective of the route of infection or serotype, there were positive associations between the viral loads in blood and the induction of host innate pro-inflammatory cytokines and acute phase proteins. Viral loads in blood and tonsil swabs were tightly correlated during the acute phase of the infection, however, viraemia significantly declined after a peak at four days post-infection (dpi), which correlated with the presence of detectable neutralising antibodies. In contrast, infectious virus was isolated in the tonsil swabs until the last sampling point (30 dpi) in most animals. The pattern of virus detection in serum and tonsil swabs was similar for all three serotypes in the direct challenged and contact challenged animals. We have demonstrated for the first time that African buffalo are indeed systemically affected by FMD virus and clinical FMD in buffalo is characterized by a transient pyrexia. Despite the lack of FMD lesions, infection of African buffalo was characterised by high viral loads in blood and oropharynx, rapid and strong host innate and adaptive immune responses and high transmissibility.

العلاقة: https://doi.org/10.1186/s13567-022-01076-3Test; https://doaj.org/toc/1297-9716Test; https://doaj.org/article/b822a936ea7347549e9e26c36ebbadf0Test

الإتاحة: https://doi.org/10.1186/s13567-022-01076-3Test
https://doaj.org/article/b822a936ea7347549e9e26c36ebbadf0Test

المؤلفون: Jumari Steyn, Pebetsi Motlou, Charmaine van Eeden, Marthi Pretorius, Voula I. Stivaktas, June Williams, Louwtjie P. Snyman, Peter E. Buss, Brianna Beechler, Anna Jolles, Eva Perez-Martin, Jan G. Myburgh, Johan Steyl, Marietjie Venter

المصدر: Emerging Infectious Diseases, Vol 26, Iss 7, Pp 1521-1525 (2020)

مصطلحات موضوعية: Domestic animals, neurological disease, orthobunyavirus, RT-PCR, Shuni virus, South Africa, Medicine, Infectious and parasitic diseases, RC109-216

الوصف: We screened nonequine animals with unexplained neurologic signs or death in South Africa during 2010–2018 for Shuni virus (SHUV). SHUV was detected in 3.3% of wildlife, 1.1% of domestic, and 2.0% of avian species. Seropositivity was also demonstrated in wildlife. These results suggest a range of possible SHUV hosts in Africa.

العلاقة: https://wwwnc.cdc.gov/eid/article/26/7/19-0770_articleTest; https://doaj.org/toc/1080-6040Test; https://doaj.org/toc/1080-6059Test; https://doaj.org/article/42ebf8cd3a5642bd9cb5480d7d1179bdTest

الإتاحة: https://doi.org/10.3201/eid2607.190770Test
https://doaj.org/article/42ebf8cd3a5642bd9cb5480d7d1179bdTest

المؤلفون: Bryan Charleston, Ginette Wilsden, Julian Seago, Ben Jackson, Yongjie Harvey, Eva Pérez-Martín, Nicholas Juleff

المصدر: Vaccine

مصطلحات موضوعية: Serotype, animal diseases, viruses, Serogroup, Article, Virus, Serology, Vaccine strain, medicine, Animals, Strain stability, General Veterinary, General Immunology and Microbiology, biology, Foot-and-mouth disease, Foot-and-mouth disease virus, Public Health, Environmental and Occupational Health, virus diseases, Viral Vaccines, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, medicine.disease, Virology, Vaccination, Infectious Diseases, Capsid, Virus neutralisation test, Foot-and-Mouth Disease, Molecular Medicine, Capsid Proteins, FMD vaccine, human activities

الوصف: Highlights • Development of improved FMD vaccines for East Africa. • Selection of candidate FMDV vaccine strains based on stability and serology. • Stability diversity between and within FMDV serotypes.
Foot-and-mouth disease (FMD) is a global burden on the livestock industry. The causative agent, FMD virus (FMDV), is highly infectious and exists in seven distinct serotypes. Vaccination remains the most effective control strategy in endemic regions and current FMD vaccines are made from inactivated preparations of whole virus. The inherent instability of FMDV and the emergence of new strains presents challenges to efficacious vaccine development. Currently, vaccines available in East Africa are comprised of relatively historic strains with unreported stabilities. As an initial step to produce an improved multivalent FMD vaccine we have identified naturally stable East African FMDV strains for each of the A, O, SAT1 and SAT2 serotypes and investigated their potential for protecting ruminants against strains that have recently circulated in East Africa. Interestingly, high diversity in stability between and within serotypes was observed, and in comparison to non-African A serotype viruses reported to date, the East African strains tested in this study are less stable. Candidate vaccine strains were adapted to propagation in BHK-21 cells with minimal capsid changes and used to generate vaccinate sera that effectively neutralised a panel of FMDV strains selected to improve FMD vaccines used in East Africa. This work highlights the importance of combining tools to predict and assess FMDV vaccine stability, with cell culture adaptation and serological tests in the development of FMD vaccines.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::170dea3f81dce73d81722d238d1f0c1eTest
https://doi.org/10.1016/j.vaccine.2021.07.001Test

المؤلفون: Caroline K. Glidden, Brianna Beechler, Peter Erik Buss, Bryan Charleston, Lin-Mari de Klerk-Lorist, Francois Frederick Maree, Timothy Muller, Eva Pérez-Martin, Katherine Anne Scott, Ockert Louis van Schalkwyk, Anna Jolles

المصدر: Frontiers in Immunology, Vol 8 (2018)

مصطلحات موضوعية: emerging infectious disease, disease surveillance, wildlife, inflammation, haptoglobin, serum amyloid A, Immunologic diseases. Allergy, RC581-607

الوصف: Detecting exposure to new or emerging pathogens is a critical challenge to protecting human, domestic animal, and wildlife health. Yet, current techniques to detect infections typically target known pathogens of humans or economically important animals. In the face of the current surge in infectious disease emergence, non-specific disease surveillance tools are urgently needed. Tracking common host immune responses indicative of recent infection may have potential as a non-specific diagnostic approach for disease surveillance. The challenge to immunologists is to identify the most promising markers, which ideally should be highly conserved across pathogens and host species, become upregulated rapidly and consistently in response to pathogen invasion, and remain elevated beyond clearance of infection. This study combined an infection experiment and a longitudinal observational study to evaluate the utility of non-specific markers of inflammation [NSMI; two acute phase proteins (haptoglobin and serum amyloid A), two pro-inflammatory cytokines (IFNγ and TNF-α)] as indicators of pathogen exposure in a wild mammalian species, African buffalo (Syncerus caffer). Specifically, in the experimental study, we asked (1) How quickly do buffalo mount NSMI responses upon challenge with an endemic pathogen, foot-and-mouth disease virus; (2) for how long do NSMI remain elevated after viral clearance and; (3) how pronounced is the difference between peak NSMI concentration and baseline NSMI concentration? In the longitudinal study, we asked (4) Are elevated NSMI associated with recent exposure to a suite of bacterial and viral respiratory pathogens in a wild population? Among the four NSMI that we tested, haptoglobin showed the strongest potential as a surveillance marker in African buffalo: concentrations quickly and consistently reached high levels in response to experimental infection, remaining elevated for almost a month. Moreover, elevated haptoglobin was indicative of recent exposure to two respiratory pathogens assessed ...

العلاقة: http://journal.frontiersin.org/article/10.3389/fimmu.2017.01944/fullTest; https://doaj.org/toc/1664-3224Test; https://doaj.org/article/37cf29d91bab4099b0d8ca215caf8169Test

الإتاحة: https://doi.org/10.3389/fimmu.2017.01944Test
https://doaj.org/article/37cf29d91bab4099b0d8ca215caf8169Test