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John Stanley - One of the best experts on this subject based on the ideXlab platform.

  • replication promiscuity of dna beta satellites associated with monopartite begomoviruses deletion mutagenesis of the ageratum yellow vein virus dna beta satellite localizes sequences involved in replication
    Journal of General Virology, 2008
    Co-Authors: Keith Saunders, Rob W Briddon, John Stanley
    Abstract:

    Pseudorecombination studies in Nicotiana benthamiana demonstrate that Ageratum yellow vein virus (AYVV) and Eupatorium yellow vein virus (EpYVV) can functionally interact with DNA-beta satellites associated with AYVV, EpYVV, cotton leaf curl Multan virus (CLCuMV) and honeysuckle yellow vein virus (HYVV). In contrast, CLCuMV shows some specificity in its ability to interact with distinct satellites and HYVV is able to interact only with its own satellite. Using an N. benthamiana leaf disk assay, we have demonstrated that HYVV is unable to trans-replicate other satellites. To investigate the basis of trans-replication compatibility, deletion mutagenesis of AYVV DNA-beta has been used to localize the origin of replication to approximately 360 nt, encompassing the ubiquitous nonanucleotide/stem-loop structure, satellite conserved Region (SCR) and part of the Intergenic Region immediately upstream of the SCR. Additional deletions within this Intergenic Region have identified a Region that is essential for replication. The capacity for DNA-beta satellites to functionally interact with distinct geminivirus species and its implications for disease diversification are discussed.

  • replication promiscuity of dna β satellites associated with monopartite begomoviruses deletion mutagenesis of the ageratum yellow vein virus dna β satellite localizes sequences involved in replication
    Journal of General Virology, 2008
    Co-Authors: Keith Saunders, Rob W Briddon, John Stanley
    Abstract:

    Pseudorecombination studies in Nicotiana benthamiana demonstrate that Ageratum yellow vein virus (AYVV) and Eupatorium yellow vein virus (EpYVV) can functionally interact with DNA-β satellites associated with AYVV, EpYVV, cotton leaf curl Multan virus (CLCuMV) and honeysuckle yellow vein virus (HYVV). In contrast, CLCuMV shows some specificity in its ability to interact with distinct satellites and HYVV is able to interact only with its own satellite. Using an N. benthamiana leaf disk assay, we have demonstrated that HYVV is unable to trans-replicate other satellites. To investigate the basis of trans-replication compatibility, deletion mutagenesis of AYVV DNA-β has been used to localize the origin of replication to approximately 360 nt, encompassing the ubiquitous nonanucleotide/stem–loop structure, satellite conserved Region (SCR) and part of the Intergenic Region immediately upstream of the SCR. Additional deletions within this Intergenic Region have identified a Region that is essential for replication. The capacity for DNA-β satellites to functionally interact with distinct geminivirus species and its implications for disease diversification are discussed.

Ayse Cefle - One of the best experts on this subject based on the ideXlab platform.

  • genetic association of a gain of function interferon gamma receptor 1 ifngr1 polymorphism and the Intergenic Region lncarod dkk1 with behcet s disease
    Arthritis & Rheumatism, 2021
    Co-Authors: Lourdes Ortiz Fernandez, Patrick Coit, Vuslat Yilmaz, Sibel P Yentur, Fatma Alibazoner, Kenan Aksu, Eren Erken, Nursen Duzgun, Gokhan Keser, Ayse Cefle
    Abstract:

    Objective Behcet's disease is a complex systemic inflammatory vasculitis of incompletely understood etiology. We performed a large genetic study in Behcet's disease in a diverse multi-ethnic population. Methods A total of 9,444 patients and controls from seven different populations were included in this study. Genotyping was performed using the Infinium ImmunoArray-24 V.1.0 or V.2.0 BeadChip. Analysis of expression data from stimulated monocytes, and epigenetic and chromatin interaction analyses were performed. Results We identified two novel genetic susceptibility loci for Behcet's disease, including a risk locus in IFNGR1 (rs4896243, p value= 2.42 X 10-9 ; OR=1.25) and within the Intergenic Region LNCAROD/DKK1 (rs1660760, p value= 2.75 x 10-8 ; OR= 0.78). The risk variants in IFNGR1 significantly increase IFNGR1 mRNA expression in lipopolysaccharide-stimulated monocytes. In addition, our results replicated the association (p value 30 genetic susceptibility loci with a suggestive level of association (p value Conclusion We performed the largest genetic association study in Behcet's disease to date and revealed novel putative functional variants associated with the disease. We also replicate and extend the genetic associations in other loci across multiple ancestries.

  • genetic association of a gain of function interferon gamma receptor 1 ifngr1 polymorphism and the Intergenic Region lncarod dkk1 with behcet s disease
    Arthritis & Rheumatism, 2021
    Co-Authors: Lourdes Ortiz Fernandez, Patrick Coit, Vuslat Yilmaz, Sibel P Yentur, Fatma Alibazoner, Kenan Aksu, Eren Erken, Nursen Duzgun, Gokhan Keser, Ayse Cefle
    Abstract:

    OBJECTIVE Behcet's disease is a complex systemic inflammatory vasculitis of incompletely understood etiology. We performed a large genetic study in Behcet's disease in a diverse multi-ethnic population. METHODS A total of 9,444 patients and controls from seven different populations were included in this study. Genotyping was performed using the Infinium ImmunoArray-24 V.1.0 or V.2.0 BeadChip. Analysis of expression data from stimulated monocytes, and epigenetic and chromatin interaction analyses were performed. RESULTS We identified two novel genetic susceptibility loci for Behcet's disease, including a risk locus in IFNGR1 (rs4896243, p value= 2.42 X 10-9 ; OR=1.25) and within the Intergenic Region LNCAROD/DKK1 (rs1660760, p value= 2.75 x 10-8 ; OR= 0.78). The risk variants in IFNGR1 significantly increase IFNGR1 mRNA expression in lipopolysaccharide-stimulated monocytes. In addition, our results replicated the association (p value 30 genetic susceptibility loci with a suggestive level of association (p value< 5 x 10-5 ), which will require replication. Finally, functional annotation of genetic susceptibility loci in Behcet's disease uncovered their possible regulatory roles and suggested potential causal genes and molecular mechanisms that could be further investigated. CONCLUSION We performed the largest genetic association study in Behcet's disease to date and revealed novel putative functional variants associated with the disease. We also replicate and extend the genetic associations in other loci across multiple ancestries.

Milton A Typas - One of the best experts on this subject based on the ideXlab platform.

  • phylogenetic and biogeographic implications inferred by mitochondrial Intergenic Region analyses and its1 5 8s its2 of the entomopathogenic fungi beauveria bassiana and b brongniartii
    BMC Microbiology, 2010
    Co-Authors: Dimitri V Ghikas, Vassili N Kouvelis, Milton A Typas
    Abstract:

    Background The entomopathogenic fungi of the genus Beauveria are cosmopolitan with a variety of different insect hosts. The two most important species, B. bassiana and B. brongniartii, have already been used as biological control agents of pests in agriculture and as models for the study of insect host - pathogen interactions. Mitochondrial (mt) genomes, due to their properties to evolve faster than the nuclear DNA, to contain introns and mobile elements and to exhibit extended polymorphisms, are ideal tools to examine genetic diversity within fungal populations and genetically identify a species or a particular isolate. Moreover, mt Intergenic Region can provide valuable phylogenetic information to study the biogeography of the fungus.

  • phylogenetic and biogeographic implications inferred by mitochondrial Intergenic Region analyses and its1 5 8s its2 of the entomopathogenic fungi beauveria bassiana and b brongniartii
    BMC Microbiology, 2010
    Co-Authors: Dimitri V Ghikas, Vassili N Kouvelis, Milton A Typas
    Abstract:

    The entomopathogenic fungi of the genus Beauveria are cosmopolitan with a variety of different insect hosts. The two most important species, B. bassiana and B. brongniartii, have already been used as biological control agents of pests in agriculture and as models for the study of insect host - pathogen interactions. Mitochondrial (mt) genomes, due to their properties to evolve faster than the nuclear DNA, to contain introns and mobile elements and to exhibit extended polymorphisms, are ideal tools to examine genetic diversity within fungal populations and genetically identify a species or a particular isolate. Moreover, mt Intergenic Region can provide valuable phylogenetic information to study the biogeography of the fungus. The complete mt genomes of B. bassiana (32,263 bp) and B. brongniartii (33,920 bp) were fully analysed. Apart from a typical gene content and organization, the Beauveria mt genomes contained several introns and had longer Intergenic Regions when compared with their close relatives. The phylogenetic diversity of a population of 84 Beauveria strains -mainly B. bassiana (n = 76) - isolated from temperate, sub-tropical and tropical habitats was examined by analyzing the nucleotide sequences of two mt Intergenic Regions (atp 6-rns and nad 3-atp 9) and the nuclear ITS1-5.8S-ITS2 domain. Mt sequences allowed better differentiation of strains than the ITS Region. Based on mt and the concatenated dataset of all genes, the B. bassiana strains were placed into two main clades: (a) the B. bassiana s. l. and (b) the "pseudobassiana". The combination of molecular phylogeny with criteria of geographic and climatic origin showed for the first time in entomopathogenic fungi, that the B. bassiana s. l. can be subdivided into seven clusters with common climate characteristics. This study indicates that mt genomes and in particular Intergenic Regions provide molecular phylogeny tools that combined with criteria of geographic and climatic origin can subdivide the B. bassiana s.l. entomopathogenic fungi into seven clusters with common climate characteristics.

Elena Postnikova - One of the best experts on this subject based on the ideXlab platform.

  • a lassa virus live attenuated vaccine candidate based on rearrangement of the Intergenic Region
    Mbio, 2020
    Co-Authors: Yingyun Cai, David X Liu, Randy Hart, Masaharu Iwasaki, Daisuke Motooka, Kurt Cooper, Ricky Adams, Tracey Burdette, Elena Postnikova
    Abstract:

    Lassa virus (LASV) poses a significant public health problem within the Regions of Lassa fever endemicity in Western Africa. LASV infects several hundred thousand individuals yearly, and a considerable number of Lassa fever cases are associated with high morbidity and lethality. No approved LASV vaccine is available, and current therapy is limited to an off-label usage of ribavirin that is only partially effective and associated with significant side effects. The impact of Lassa fever on human health, together with the limited existing countermeasures, highlights the importance of developing effective vaccines against LASV. Here, we present the development and characterization of a recombinant LASV (rLASV) vaccine candidate [rLASV(IGR/S-S)], which is based on the presence of the noncoding Intergenic Region (IGR) of the small (S) genome segment (S-IGR) in both large (L) and S LASV segments. In cultured cells, rLASV(IGR/S-S) was modestly less fit than wild-type rLASV (rLASV-WT). rLASV(IGR/S-S) was highly attenuated in guinea pigs, and a single subcutaneous low dose of the virus completely protected against otherwise lethal infection with LASV-WT. Moreover, rLASV(IGR/S-S) was genetically stable during serial passages in cultured cells. These findings indicate that rLASV(IGR/S-S) can be developed into a LASV live-attenuated vaccine (LAV) that has the same antigenic composition as LASV-WT and a well-defined mechanism of attenuation that overcomes concerns about increased virulence that could be caused by genetic changes in the LAV during multiple rounds of multiplication.IMPORTANCE Lassa virus (LASV), the causative agent of Lassa fever, infects several hundred thousand people in Western Africa, resulting in many lethal Lassa fever cases. No U.S. Food and Drug Administration-licensed countermeasures are available to prevent or treat LASV infection. We describe the generation of a novel LASV live-attenuated vaccine candidate rLASV(IGR/S-S), which is based on the replacement of the large genomic segment noncoding Intergenic Region (IGR) with that of the small genome segment. rLASV(IGR/S-S) is less fit in cell culture than wild-type virus and does not cause clinical signs in inoculated guinea pigs. Importantly, rLASV(IGR/S-S) protects immunized guinea pigs against an otherwise lethal exposure to LASV.

  • A Lassa Virus Live-Attenuated Vaccine Candidate Based on Rearrangement of the Intergenic Region
    'American Society for Microbiology', 2020
    Co-Authors: Yingyun Cai, David X Liu, Randy Hart, Masaharu Iwasaki, Daisuke Motooka, Kurt Cooper, Ricky Adams, Tracey Burdette, Elena Postnikova
    Abstract:

    Lassa virus (LASV), the causative agent of Lassa fever, infects several hundred thousand people in Western Africa, resulting in many lethal Lassa fever cases. No U.S. Food and Drug Administration-licensed countermeasures are available to prevent or treat LASV infection. We describe the generation of a novel LASV live-attenuated vaccine candidate rLASV(IGR/S-S), which is based on the replacement of the large genomic segment noncoding Intergenic Region (IGR) with that of the small genome segment. rLASV(IGR/S-S) is less fit in cell culture than wild-type virus and does not cause clinical signs in inoculated guinea pigs. Importantly, rLASV(IGR/S-S) protects immunized guinea pigs against an otherwise lethal exposure to LASV.Lassa virus (LASV) poses a significant public health problem within the Regions of Lassa fever endemicity in Western Africa. LASV infects several hundred thousand individuals yearly, and a considerable number of Lassa fever cases are associated with high morbidity and lethality. No approved LASV vaccine is available, and current therapy is limited to an off-label usage of ribavirin that is only partially effective and associated with significant side effects. The impact of Lassa fever on human health, together with the limited existing countermeasures, highlights the importance of developing effective vaccines against LASV. Here, we present the development and characterization of a recombinant LASV (rLASV) vaccine candidate [rLASV(IGR/S-S)], which is based on the presence of the noncoding Intergenic Region (IGR) of the small (S) genome segment (S-IGR) in both large (L) and S LASV segments. In cultured cells, rLASV(IGR/S-S) was modestly less fit than wild-type rLASV (rLASV-WT). rLASV(IGR/S-S) was highly attenuated in guinea pigs, and a single subcutaneous low dose of the virus completely protected against otherwise lethal infection with LASV-WT. Moreover, rLASV(IGR/S-S) was genetically stable during serial passages in cultured cells. These findings indicate that rLASV(IGR/S-S) can be developed into a LASV live-attenuated vaccine (LAV) that has the same antigenic composition as LASV-WT and a well-defined mechanism of attenuation that overcomes concerns about increased virulence that could be caused by genetic changes in the LAV during multiple rounds of multiplication

Masaharu Iwasaki - One of the best experts on this subject based on the ideXlab platform.

  • a lassa virus live attenuated vaccine candidate based on rearrangement of the Intergenic Region
    Mbio, 2020
    Co-Authors: Yingyun Cai, David X Liu, Randy Hart, Masaharu Iwasaki, Daisuke Motooka, Kurt Cooper, Ricky Adams, Tracey Burdette, Elena Postnikova
    Abstract:

    Lassa virus (LASV) poses a significant public health problem within the Regions of Lassa fever endemicity in Western Africa. LASV infects several hundred thousand individuals yearly, and a considerable number of Lassa fever cases are associated with high morbidity and lethality. No approved LASV vaccine is available, and current therapy is limited to an off-label usage of ribavirin that is only partially effective and associated with significant side effects. The impact of Lassa fever on human health, together with the limited existing countermeasures, highlights the importance of developing effective vaccines against LASV. Here, we present the development and characterization of a recombinant LASV (rLASV) vaccine candidate [rLASV(IGR/S-S)], which is based on the presence of the noncoding Intergenic Region (IGR) of the small (S) genome segment (S-IGR) in both large (L) and S LASV segments. In cultured cells, rLASV(IGR/S-S) was modestly less fit than wild-type rLASV (rLASV-WT). rLASV(IGR/S-S) was highly attenuated in guinea pigs, and a single subcutaneous low dose of the virus completely protected against otherwise lethal infection with LASV-WT. Moreover, rLASV(IGR/S-S) was genetically stable during serial passages in cultured cells. These findings indicate that rLASV(IGR/S-S) can be developed into a LASV live-attenuated vaccine (LAV) that has the same antigenic composition as LASV-WT and a well-defined mechanism of attenuation that overcomes concerns about increased virulence that could be caused by genetic changes in the LAV during multiple rounds of multiplication.IMPORTANCE Lassa virus (LASV), the causative agent of Lassa fever, infects several hundred thousand people in Western Africa, resulting in many lethal Lassa fever cases. No U.S. Food and Drug Administration-licensed countermeasures are available to prevent or treat LASV infection. We describe the generation of a novel LASV live-attenuated vaccine candidate rLASV(IGR/S-S), which is based on the replacement of the large genomic segment noncoding Intergenic Region (IGR) with that of the small genome segment. rLASV(IGR/S-S) is less fit in cell culture than wild-type virus and does not cause clinical signs in inoculated guinea pigs. Importantly, rLASV(IGR/S-S) protects immunized guinea pigs against an otherwise lethal exposure to LASV.

  • A Lassa Virus Live-Attenuated Vaccine Candidate Based on Rearrangement of the Intergenic Region
    'American Society for Microbiology', 2020
    Co-Authors: Yingyun Cai, David X Liu, Randy Hart, Masaharu Iwasaki, Daisuke Motooka, Kurt Cooper, Ricky Adams, Tracey Burdette, Elena Postnikova
    Abstract:

    Lassa virus (LASV), the causative agent of Lassa fever, infects several hundred thousand people in Western Africa, resulting in many lethal Lassa fever cases. No U.S. Food and Drug Administration-licensed countermeasures are available to prevent or treat LASV infection. We describe the generation of a novel LASV live-attenuated vaccine candidate rLASV(IGR/S-S), which is based on the replacement of the large genomic segment noncoding Intergenic Region (IGR) with that of the small genome segment. rLASV(IGR/S-S) is less fit in cell culture than wild-type virus and does not cause clinical signs in inoculated guinea pigs. Importantly, rLASV(IGR/S-S) protects immunized guinea pigs against an otherwise lethal exposure to LASV.Lassa virus (LASV) poses a significant public health problem within the Regions of Lassa fever endemicity in Western Africa. LASV infects several hundred thousand individuals yearly, and a considerable number of Lassa fever cases are associated with high morbidity and lethality. No approved LASV vaccine is available, and current therapy is limited to an off-label usage of ribavirin that is only partially effective and associated with significant side effects. The impact of Lassa fever on human health, together with the limited existing countermeasures, highlights the importance of developing effective vaccines against LASV. Here, we present the development and characterization of a recombinant LASV (rLASV) vaccine candidate [rLASV(IGR/S-S)], which is based on the presence of the noncoding Intergenic Region (IGR) of the small (S) genome segment (S-IGR) in both large (L) and S LASV segments. In cultured cells, rLASV(IGR/S-S) was modestly less fit than wild-type rLASV (rLASV-WT). rLASV(IGR/S-S) was highly attenuated in guinea pigs, and a single subcutaneous low dose of the virus completely protected against otherwise lethal infection with LASV-WT. Moreover, rLASV(IGR/S-S) was genetically stable during serial passages in cultured cells. These findings indicate that rLASV(IGR/S-S) can be developed into a LASV live-attenuated vaccine (LAV) that has the same antigenic composition as LASV-WT and a well-defined mechanism of attenuation that overcomes concerns about increased virulence that could be caused by genetic changes in the LAV during multiple rounds of multiplication