The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Diego Cadavid - One of the best experts on this subject based on the ideXlab platform.
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high production of cxcl13 in blood and brain during Persistent Infection with the relapsing fever spirochete borrelia turicatae
Journal of Neuropathology and Experimental Neurology, 2007Co-Authors: Harald Gelderblom, Diana Londono, Adriana Marques, Yunhong Bai, Jacqueline A Quandt, Ron Hornung, Roland Martin, Erik S Cabral, Diego CadavidAbstract:Relapsing fever (RF) is a multisystemic borrelial Infection with frequent neurologic involvement referred to as neuroborreliosis. The absence of an effective antibody response results in Persistent Infection. To study the consequences to the brain of Persistent Infection with the RF spirochete Borrelia turicatae, we studied B cell (Igh6-/-) and B and T (Rag1-/-) cell-deficient mice inoculated with isogenic serotypes 1 (Bt1) or 2 (Bt2). We found that Bt1 was more tissue tropic than Bt2, not only for brain but also for heart. Igh6-/- mice developed more severe clinical disease than Rag1-/- mice. Bt1-infected brains had widespread microgliosis/brain macrophage activation despite localization of spirochetes in the leptomeninges rather than the brain parenchyma itself. Oligoarray analysis revealed that CXCL13 was the most upregulated gene in the brain of Bt1-infected Igh6-/- mice. CXCL13 was also the most abundant of the chemokines we measured in infected blood. Persistent Infection did not result in injury to the brain. Treatment with exogenous interleukin-10 reduced microgliosis in the brain and production of CXCL13 in the blood. We concluded that brain involvement in B cell-deficient mice Persistently infected with B. turicatae is characterized by prominent microgliosis and production of CXCL13 without detectable injury.
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role of interleukin 10 during Persistent Infection with the relapsing fever spirochete borrelia turicatae
American Journal of Pathology, 2007Co-Authors: Diana Londono, Adriana Marques, Harald Gelderblom, Jens Schmidt, Yunhong Bai, Jacqueline A Quandt, Ron Hornung, Roland Martin, Diego CadavidAbstract:Relapsing fever is an Infection characterized by peaks of spirochetemia attributable to antibody selection against variable serotypes. In the absence of B cells, serotypes cannot be cleared, resulting in Persistent Infection. We previously identified differences in spirochetemia and disease severity during Persistent Infection of severe combined immunodeficiency mice with isogenic serotypes 1 (Bt1) or 2 (Bt2) of Borrelia turicatae. To investigate this further, we studied pathogen load, clinical disease, cytokine/chemokine production, and inflammation in mice deficient in B (Igh6−/−) or B and T (Rag1−/−) cells Persistently infected with Bt1 or Bt2. The results showed that Igh6−/− mice, despite lower spirochetemia, had a significantly aggravated disease course compared with Rag1−/− mice. Measurement of cytokines revealed a significant positive correlation between pathogen load and interleukin (IL)-10 in blood, brain, and heart. Bt2-infected Rag1−/− mice harbored the highest spirochetemia and, at the same time, displayed the highest IL-10 plasma levels. In the brain, Bt1, which was five times more neurotropic than Bt2, caused higher IL-10 production. Activated microglia were the main source of IL-10 in brain. IL-10 injected systemically reduced disease and spirochetemia. The results suggest IL-10 plays a protective role as a down-regulator of inflammation and pathogen load during Infection with relapsing fever spirochetes.
Harald Gelderblom - One of the best experts on this subject based on the ideXlab platform.
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high production of cxcl13 in blood and brain during Persistent Infection with the relapsing fever spirochete borrelia turicatae
Journal of Neuropathology and Experimental Neurology, 2007Co-Authors: Harald Gelderblom, Diana Londono, Adriana Marques, Yunhong Bai, Jacqueline A Quandt, Ron Hornung, Roland Martin, Erik S Cabral, Diego CadavidAbstract:Relapsing fever (RF) is a multisystemic borrelial Infection with frequent neurologic involvement referred to as neuroborreliosis. The absence of an effective antibody response results in Persistent Infection. To study the consequences to the brain of Persistent Infection with the RF spirochete Borrelia turicatae, we studied B cell (Igh6-/-) and B and T (Rag1-/-) cell-deficient mice inoculated with isogenic serotypes 1 (Bt1) or 2 (Bt2). We found that Bt1 was more tissue tropic than Bt2, not only for brain but also for heart. Igh6-/- mice developed more severe clinical disease than Rag1-/- mice. Bt1-infected brains had widespread microgliosis/brain macrophage activation despite localization of spirochetes in the leptomeninges rather than the brain parenchyma itself. Oligoarray analysis revealed that CXCL13 was the most upregulated gene in the brain of Bt1-infected Igh6-/- mice. CXCL13 was also the most abundant of the chemokines we measured in infected blood. Persistent Infection did not result in injury to the brain. Treatment with exogenous interleukin-10 reduced microgliosis in the brain and production of CXCL13 in the blood. We concluded that brain involvement in B cell-deficient mice Persistently infected with B. turicatae is characterized by prominent microgliosis and production of CXCL13 without detectable injury.
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role of interleukin 10 during Persistent Infection with the relapsing fever spirochete borrelia turicatae
American Journal of Pathology, 2007Co-Authors: Diana Londono, Adriana Marques, Harald Gelderblom, Jens Schmidt, Yunhong Bai, Jacqueline A Quandt, Ron Hornung, Roland Martin, Diego CadavidAbstract:Relapsing fever is an Infection characterized by peaks of spirochetemia attributable to antibody selection against variable serotypes. In the absence of B cells, serotypes cannot be cleared, resulting in Persistent Infection. We previously identified differences in spirochetemia and disease severity during Persistent Infection of severe combined immunodeficiency mice with isogenic serotypes 1 (Bt1) or 2 (Bt2) of Borrelia turicatae. To investigate this further, we studied pathogen load, clinical disease, cytokine/chemokine production, and inflammation in mice deficient in B (Igh6−/−) or B and T (Rag1−/−) cells Persistently infected with Bt1 or Bt2. The results showed that Igh6−/− mice, despite lower spirochetemia, had a significantly aggravated disease course compared with Rag1−/− mice. Measurement of cytokines revealed a significant positive correlation between pathogen load and interleukin (IL)-10 in blood, brain, and heart. Bt2-infected Rag1−/− mice harbored the highest spirochetemia and, at the same time, displayed the highest IL-10 plasma levels. In the brain, Bt1, which was five times more neurotropic than Bt2, caused higher IL-10 production. Activated microglia were the main source of IL-10 in brain. IL-10 injected systemically reduced disease and spirochetemia. The results suggest IL-10 plays a protective role as a down-regulator of inflammation and pathogen load during Infection with relapsing fever spirochetes.
M H T Troedsson - One of the best experts on this subject based on the ideXlab platform.
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intrahost selection pressure drives equine arteritis virus evolution during Persistent Infection in the stallion reproductive tract
Journal of Virology, 2019Co-Authors: Bora Nam, Zelalem Mekuria, Mariano Carossino, Ying Zheng, Jianqiang Zhang, Frank R Cook, Kathleen M Shuck, J R Campos, E L Squires, M H T TroedssonAbstract:Equine arteritis virus (EAV) is the causative agent of equine viral arteritis (EVA), a reproductive and respiratory disease of horses. Following natural Infection, 10 to 70% of infected stallions can become carriers of EAV and continue to shed virus in the semen. In this study, sequential viruses isolated from nasal secretions, buffy coat cells, and semen of seven experimentally infected and two naturally infected EAV carrier stallions were deep sequenced to elucidate the intrahost microevolutionary process after a single transmission event. Analysis of variants from nasal secretions and buffy coat cells lacked extensive positive selection; however, characteristics of the mutant spectra were different in the two sample types. In contrast, the initial semen virus populations during acute Infection have undergone a selective bottleneck, as reflected by the reduction in population size and diversifying selection at multiple sites in the viral genome. Furthermore, during Persistent Infection, extensive genome-wide purifying selection shaped variant diversity in the stallion reproductive tract. Overall, the nonstochastic nature of EAV evolution during Persistent Infection was driven by active intrahost selection pressure. Among the open reading frames within the viral genome, ORF3, ORF5, and the nsp2-coding region of ORF1a accumulated the majority of nucleotide substitutions during persistence, with ORF3 and ORF5 having the highest intrahost evolutionary rates. The findings presented here provide a novel insight into the evolutionary mechanisms of EAV and identified critical regions of the viral genome likely associated with the establishment and maintenance of Persistent Infection in the stallion reproductive tract.IMPORTANCE EAV can persist in the reproductive tract of infected stallions, and consequently, long-term carrier stallions constitute its sole natural reservoir. Previous studies demonstrated that the ampullae of the vas deferens are the primary site of viral persistence in the stallion reproductive tract and the persistence is associated with a significant inflammatory response that is unable to clear the Infection. This is the first study that describes EAV full-length genomic evolution during acute and long-term Persistent Infection in the stallion reproductive tract using next-generation sequencing and contemporary sequence analysis techniques. The data provide novel insight into the intrahost evolution of EAV during acute and Persistent Infection and demonstrate that Persistent Infection is characterized by extensive genome-wide purifying selection and a nonstochastic evolutionary pattern mediated by intrahost selective pressure, with important nucleotide substitutions occurring in ORF1a (region encoding nsp2), ORF3, and ORF5.
Nadezda Urosevic - One of the best experts on this subject based on the ideXlab platform.
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characterization of defective viral rna produced during Persistent Infection of vero cells with murray valley encephalitis virus
Journal of Virology, 1998Co-Authors: Morag U Lancaster, John S. Mackenzie, Stuart I Hodgetts, Nadezda UrosevicAbstract:Defective interfering viral particles are readily produced in cell culture after a high multiplicity of Infection with many animal RNA viruses. Due to defects that they carry in their genomes, their life cycle needs to be complemented by the helper functions provided by a parental virus which makes them both dependent on and competitive with the parental virus. In many instances, this may cause the abrogation of a lytic cycle of the parental virus, leading to a Persistent Infection. In this paper, we describe for the first time the presence of truncated or defective interfering viral RNAs produced in Vero cells Persistently infected with the flavivirus Murray Valley encephalitis virus. While these RNAs have not been detected in acutely infected Vero cells, their appearance coincided with the establishment of Persistent Infection. We also show for the first time that the defective viral RNAs replicate well in both cell culture and cell-free virus replication systems, indicating that they may interfere with the replication of parental virus at the level of viral RNA synthesis. Significantly, structural analyses of these RNA species including nucleotide sequencing have revealed that they carry similar nucleotide deletions encompassing the genes coding for the prM and E proteins and various gene segments coding for the N terminus of the NS1 protein. These deletions are in frame, allowing the synthesis of truncated NS1 proteins to occur in Persistently infected cells. This may have further implications for the interference with the parental virus at the level of viral RNA synthesis in addition to a major one at the level of virion assembly and release.
Diana Londono - One of the best experts on this subject based on the ideXlab platform.
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high production of cxcl13 in blood and brain during Persistent Infection with the relapsing fever spirochete borrelia turicatae
Journal of Neuropathology and Experimental Neurology, 2007Co-Authors: Harald Gelderblom, Diana Londono, Adriana Marques, Yunhong Bai, Jacqueline A Quandt, Ron Hornung, Roland Martin, Erik S Cabral, Diego CadavidAbstract:Relapsing fever (RF) is a multisystemic borrelial Infection with frequent neurologic involvement referred to as neuroborreliosis. The absence of an effective antibody response results in Persistent Infection. To study the consequences to the brain of Persistent Infection with the RF spirochete Borrelia turicatae, we studied B cell (Igh6-/-) and B and T (Rag1-/-) cell-deficient mice inoculated with isogenic serotypes 1 (Bt1) or 2 (Bt2). We found that Bt1 was more tissue tropic than Bt2, not only for brain but also for heart. Igh6-/- mice developed more severe clinical disease than Rag1-/- mice. Bt1-infected brains had widespread microgliosis/brain macrophage activation despite localization of spirochetes in the leptomeninges rather than the brain parenchyma itself. Oligoarray analysis revealed that CXCL13 was the most upregulated gene in the brain of Bt1-infected Igh6-/- mice. CXCL13 was also the most abundant of the chemokines we measured in infected blood. Persistent Infection did not result in injury to the brain. Treatment with exogenous interleukin-10 reduced microgliosis in the brain and production of CXCL13 in the blood. We concluded that brain involvement in B cell-deficient mice Persistently infected with B. turicatae is characterized by prominent microgliosis and production of CXCL13 without detectable injury.
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role of interleukin 10 during Persistent Infection with the relapsing fever spirochete borrelia turicatae
American Journal of Pathology, 2007Co-Authors: Diana Londono, Adriana Marques, Harald Gelderblom, Jens Schmidt, Yunhong Bai, Jacqueline A Quandt, Ron Hornung, Roland Martin, Diego CadavidAbstract:Relapsing fever is an Infection characterized by peaks of spirochetemia attributable to antibody selection against variable serotypes. In the absence of B cells, serotypes cannot be cleared, resulting in Persistent Infection. We previously identified differences in spirochetemia and disease severity during Persistent Infection of severe combined immunodeficiency mice with isogenic serotypes 1 (Bt1) or 2 (Bt2) of Borrelia turicatae. To investigate this further, we studied pathogen load, clinical disease, cytokine/chemokine production, and inflammation in mice deficient in B (Igh6−/−) or B and T (Rag1−/−) cells Persistently infected with Bt1 or Bt2. The results showed that Igh6−/− mice, despite lower spirochetemia, had a significantly aggravated disease course compared with Rag1−/− mice. Measurement of cytokines revealed a significant positive correlation between pathogen load and interleukin (IL)-10 in blood, brain, and heart. Bt2-infected Rag1−/− mice harbored the highest spirochetemia and, at the same time, displayed the highest IL-10 plasma levels. In the brain, Bt1, which was five times more neurotropic than Bt2, caused higher IL-10 production. Activated microglia were the main source of IL-10 in brain. IL-10 injected systemically reduced disease and spirochetemia. The results suggest IL-10 plays a protective role as a down-regulator of inflammation and pathogen load during Infection with relapsing fever spirochetes.
