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Mariano Esteban - One of the best experts on this subject based on the ideXlab platform.
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proteomics analysis reveals that structural proteins of the virion core and involved in gene expression are the main source for hla class ii ligands in vaccinia virus infected cells
Journal of Proteome Research, 2019Co-Authors: Elena Lorente, Pilar Lauzurica, Eilon Barnea, Alejandro Barriga, Carmen Mir, Mariano Esteban, Antonio J Martingaliano, Concepcion Palomo, Juan Garciaarriaza, Arie AdmonAbstract:Protective cellular and humoral immune responses require previous recognition of viral antigenic peptides complexed with human leukocyte antigen (HLA) class II molecules on the surface of the antigen presenting cells. The HLA class II-restricted immune response is important for the control and the clearance of Poxvirus Infection including vaccinia virus (VACV), the vaccine used in the worldwide eradication of smallpox. In this study, a mass spectrometry analysis was used to identify VACV ligands bound to HLA-DR and -DP class II molecules present on the surface of VACV-infected cells. Twenty-six naturally processed viral ligands among the tens of thousands of cell peptides bound to HLA class II proteins were identified. These viral ligands arose from 19 parental VACV proteins: A4, A5, A18, A35, A38, B5, B13, D1, D5, D7, D12, D13, E3, E8, H5, I2, I3, J2, and K2. The majority of these VACV proteins yielded one HLA ligand and were generated mainly, but not exclusively, by the classical HLA class II antigen processing pathway. Medium-sized and abundant proteins from the virion core and/or involved in the viral gene expression were the major source of VACV ligands bound to HLA-DR and -DP class II molecules. These findings will help to understand the effectiveness of current Poxvirus-based vaccines and will be important in the design of new ones.
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Proteomics Analysis Reveals That Structural Proteins of the Virion Core and Involved in Gene Expression Are the Main Source for HLA Class II Ligands in Vaccinia Virus-Infected Cells
2019Co-Authors: Elena Lorente, Pilar Lauzurica, Antonio J. Martín-galiano, Eilon Barnea, Alejandro Barriga, Concepción Palomo, Juan García-arriaza, Carmen Mir, Mariano Esteban, Arie AdmonAbstract:Protective cellular and humoral immune responses require previous recognition of viral antigenic peptides complexed with human leukocyte antigen (HLA) class II molecules on the surface of the antigen presenting cells. The HLA class II-restricted immune response is important for the control and the clearance of Poxvirus Infection including vaccinia virus (VACV), the vaccine used in the worldwide eradication of smallpox. In this study, a mass spectrometry analysis was used to identify VACV ligands bound to HLA-DR and -DP class II molecules present on the surface of VACV-infected cells. Twenty-six naturally processed viral ligands among the tens of thousands of cell peptides bound to HLA class II proteins were identified. These viral ligands arose from 19 parental VACV proteins: A4, A5, A18, A35, A38, B5, B13, D1, D5, D7, D12, D13, E3, E8, H5, I2, I3, J2, and K2. The majority of these VACV proteins yielded one HLA ligand and were generated mainly, but not exclusively, by the classical HLA class II antigen processing pathway. Medium-sized and abundant proteins from the virion core and/or involved in the viral gene expression were the major source of VACV ligands bound to HLA-DR and -DP class II molecules. These findings will help to understand the effectiveness of current Poxvirus-based vaccines and will be important in the design of new ones
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mc159l protein from the Poxvirus molluscum contagiosum virus inhibits nf kappab activation and apoptosis induced by pkr
Journal of General Virology, 2001Co-Authors: Jesus Gil, Joaquin Rullas, Jose Alcami, Mariano EstebanAbstract:Molluscum contagiosum virus (MCV) is a human Poxvirus that causes abnormal proliferation of epithelial cells. MCV encodes specific molecules to control host defences, such as MC159L, which as previously shown prevents apoptosis induced by death receptors. However, unlike most Poxviruses, MCV lacks a homologue to the E3L and K3L proteins of vaccinia virus, which are involved in the control of the key antiviral and pro-apoptotic dsRNA-dependent protein kinase, PKR. In this study, we analysed the relationship of MC159L to PKR. We found that MC159L is not a direct inhibitor of PKR since it does not associate with PKR and cannot block PKR-induced phosphorylation of eIF-2α. However, expression of MC159L inhibits apoptosis triggered by PKR through death receptor-mediated pathways. In addition, MC159L inhibits NF-κB activation induced in response to PKR. Expression of MC159L cannot counteract the PKR-mediated antiviral action in the context of a Poxvirus Infection, despite its ability to affect these signalling events. These findings show that MC159L is able to interfere with downstream events triggered by PKR in the absence of a direct physical interaction, and assign a role to MC159L in the control of some PKR-mediated biological effects.
Felix N Toka - One of the best experts on this subject based on the ideXlab platform.
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ectromelia virus suppresses expression of cathepsins and cystatins in conventional dendritic cells to efficiently execute the replication process
BMC Microbiology, 2019Co-Authors: Magdalena Bossowskanowicka, Malgorzata Gierynska, Karolina P Gregorczykzboroch, Matylda B Mielcarska, Justyna Struzik, Felix N Toka, Marta Romaniewicz, Monika M Kaczmarek, Marta GrodzikAbstract:Cathepsins are a group of endosomal proteases present in many cells including dendritic cells (DCs). The activity of cathepsins is regulated by their endogenous inhibitors – cystatins. Cathepsins are crucial to antigen processing during viral and bacterial Infections, and as such are a prerequisite to antigen presentation in the context of major histocompatibility complex class I and II molecules. Due to the involvement of DCs in both innate and adaptive immune responses, and the quest to understand the impact of Poxvirus Infection on host cells, we investigated the influence of ectromelia virus (ECTV) Infection on cathepsin and cystatin levels in murine conventional DCs (cDCs). ECTV is a Poxvirus that has evolved many mechanisms to avoid host immune response and is able to replicate productively in DCs. Our results showed that ECTV-Infection of JAWS II DCs and primary murine GM-CSF-derived bone marrow cells down-regulated both mRNA and protein of cathepsin B, L and S, and cystatin B and C, particularly during the later stages of Infection. Moreover, the activity of cathepsin B, L and S was confirmed to be diminished especially at later stages of Infection in JAWS II cells. Consequently, ECTV-infected DCs had diminished ability to endocytose and process a soluble antigen. Close examination of cellular protein distribution showed that beginning from early stages of Infection, the remnants of cathepsin L and cystatin B co-localized and partially co-localized with viral replication centers (viral factories), respectively. Moreover, viral yield increased in cDCs treated with siRNA against cathepsin B, L or S and subsequently infected with ECTV. Taken together, our results indicate that Infection of cDCs with ECTV suppresses cathepsins and cystatins, and alters their cellular distribution which impairs the cDC function. We propose this as an additional viral strategy to escape immune responses, enabling the virus to replicate effectively in infected cells.
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Ectromelia virus suppresses expression of cathepsins and cystatins in conventional dendritic cells to efficiently execute the replication process
BMC, 2019Co-Authors: Magdalena Bossowska-nowicka, Malgorzata Gierynska, Matylda B Mielcarska, Justyna Struzik, Felix N Toka, Marta Romaniewicz, Monika M Kaczmarek, Marta Grodzik, Karolina P. Gregorczyk-zboroch, Lidia Szulc-dąbrowskaAbstract:Abstract Background Cathepsins are a group of endosomal proteases present in many cells including dendritic cells (DCs). The activity of cathepsins is regulated by their endogenous inhibitors – cystatins. Cathepsins are crucial to antigen processing during viral and bacterial Infections, and as such are a prerequisite to antigen presentation in the context of major histocompatibility complex class I and II molecules. Due to the involvement of DCs in both innate and adaptive immune responses, and the quest to understand the impact of Poxvirus Infection on host cells, we investigated the influence of ectromelia virus (ECTV) Infection on cathepsin and cystatin levels in murine conventional DCs (cDCs). ECTV is a Poxvirus that has evolved many mechanisms to avoid host immune response and is able to replicate productively in DCs. Results Our results showed that ECTV-Infection of JAWS II DCs and primary murine GM-CSF-derived bone marrow cells down-regulated both mRNA and protein of cathepsin B, L and S, and cystatin B and C, particularly during the later stages of Infection. Moreover, the activity of cathepsin B, L and S was confirmed to be diminished especially at later stages of Infection in JAWS II cells. Consequently, ECTV-infected DCs had diminished ability to endocytose and process a soluble antigen. Close examination of cellular protein distribution showed that beginning from early stages of Infection, the remnants of cathepsin L and cystatin B co-localized and partially co-localized with viral replication centers (viral factories), respectively. Moreover, viral yield increased in cDCs treated with siRNA against cathepsin B, L or S and subsequently infected with ECTV. Conclusions Taken together, our results indicate that Infection of cDCs with ECTV suppresses cathepsins and cystatins, and alters their cellular distribution which impairs the cDC function. We propose this as an additional viral strategy to escape immune responses, enabling the virus to replicate effectively in infected cells
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influence of ectromelia virus ectv mos Infection on mrna transcript levels of selected genes encoding antiviral proteins in a macrophage cell line raw 264 7 in vitro studies
Journal of Immunology, 2016Co-Authors: Matylda B Mielcarska, Felix N Toka, Patryk Dolega, Karolina Gregorczyk, Magdalena Bossowska, Lidia SzulcdabrowskaAbstract:Poxviruses have evolved a number of mechanisms to avoid immune response by the infected host. We investigated the impact of Poxvirus Infection on the level of mRNA transcripts of selected genes encoding antiviral proteins in the macrophage cell line (RAW 264.7). We observed reduction of mRNA transcript level in four groups of signalling pathways (Toll-like receptor signalling, NOD-like receptor signalling, RIG-I-like receptor signalling, and Type I interferon signalling) involved in innate immune response. Seventy-three genes had a statistically significantly decreased mRNA expression, 4 genes had a statistically significantly sustained mRNA expression. Only Cxcl11 and Ifna2 were statistically significantly increased. The results confirmed that the mouse Poxvirus ECTV may interfere with or inhibit many signalling pathways, which are involved in inducing an antiviral immune response in infected macrophages.
Sally R Isberg - One of the best experts on this subject based on the ideXlab platform.
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crocodilepox virus evolutionary genomics supports observed Poxvirus Infection dynamics on saltwater crocodile crocodylus porosus
Viruses, 2019Co-Authors: Subir Sarker, Lorna Melville, Sally R Isberg, Jasmin Moran, Rachel De Araujo, Nikki Elliott, Travis Clarke Beddoe, Karla J HelbigAbstract:Saltwater crocodilepox virus (SwCRV), belonging to the genus CrocodylidPoxvirus, are large DNA viruses posing an economic risk to Australian saltwater crocodile (Crocodylus porosus) farms by extending production times. Although Poxvirus-like particles and sequences have been confirmed, their Infection dynamics, inter-farm genetic variability and evolutionary relationships remain largely unknown. In this study, a Poxvirus Infection dynamics study was conducted on two C. porosus farms. One farm (Farm 2) showed twice the Infection rate, and more concerningly, an increase in the number of early- to late-stage Poxvirus lesions as crocodiles approached harvest size, reflecting the extended production periods observed on this farm. To determine if there was a genetic basis for this difference, 14 complete SwCRV genomes were isolated from lesions sourced from five Australian farms. They encompassed all the conserved genes when compared to the two previously reported SwCRV genomes and fell within three major clades. Farm 2′s SwCRV sequences were distributed across all three clades, highlighting the likely mode of inter-farm transmission. Twenty-four recombination events were detected, with one recombination event resulting in consistent fragmentation of the P4c gene in the majority of the Farm 2 SwCRV isolates. Further investigation into the evolution of Poxvirus Infection in farmed crocodiles may offer valuable insights in evolution of this viral family and afford the opportunity to obtain crucial information into natural viral selection processes in an in vivo setting.
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impact of Poxvirus lesions on saltwater crocodile crocodylus porosus skins
Veterinary Microbiology, 2017Co-Authors: Rhiannon L Moore, Sally R Isberg, Cathy M Shilton, Natalie L MilicAbstract:Abstract Cutaneous Poxvirus Infections are common in several crocodilian species and are of importance in crocodile farming due to their potential impact on the tanned hide. To confirm Poxvirus Infection and understand the impact on saltwater crocodile (Crocodylus porosus) skin, fourteen animals from different age groups (five hatchlings, five yearlings and four grow-outs) were selected based on a criterion of ten Poxvirus-like lesions per animal. One lesion on each animal was extruded for genetic analysis and transmission electron microscopy. Both methods confirmed Poxvirus so the remainder of lesions were re-examined every six weeks over a 24 week study period. Each lesion went through four distinct phases: early active, active, expulsion and healing. To understand how these lesions impact on the final skin product, one crocodile from each age group was euthanised and the lesions examined. Using standard skin grading techniques (light-table), the early phase (early active – expulsion) lesions were all translucent and would lead to downgrading of the skin or, at worst, rendering them unsaleable. At the later stages of healing, the translucency reduces. Histological examination of the phases confirm that the basement membrane is not breached by the Infection further indicating that Poxvirus lesions, given enough time, will eventually have no detrimental effect on skin quality. This is obviously dependent upon no more lesions developing in the interim.
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pathology of runting in farmed saltwater crocodiles crocodylus porosus in australia
Veterinary Pathology, 2014Co-Authors: Catherine M Shilton, L Chambers, Suresh Benedict, Steven S Davis, Shlomzion Aumann, Sally R IsbergAbstract:Extremely poor growth of some individuals within a birth cohort (runting) is a significant problem in crocodile farming. We conducted a pathological investigation to determine if infectious disease is associated with runting in farmed saltwater crocodiles (Crocodylus porosus) and to look for evidence of other etiologies. In each of 2005 and 2007, 10 normal and 10 runt crocodiles, with an average age of 5.5 months and reared under identical conditions, were sampled. Laboratory testing included postmortem; histological examination of a wide variety of tissues (with quantitation of features that were noted subjectively to be different between groups); hematology; serum biochemistry (total protein, albumin, globulins, total calcium, phosphorus, and iron); bacterial culture of liver and spleen (2005 only); viral culture of liver, thymus, tonsil, and spleen using primary crocodile cell lines (2007 only); and serum corticosterone (2007 only). The only evidence of infectious disease was mild cutaneous Poxvirus Infection in 45% of normal and 40% of runt crocodiles and rare intestinal coccidia in 5% of normal and 15% of runt crocodiles. Bacterial and viral culture did not reveal significant differences between the 2 groups. However, runt crocodiles exhibited significant (P < .05) increases in adrenocortical cell cytoplasmic vacuolation and serum corticosterone, decreased production of bone (osteoporosis), and reduced lymphoid populations in the spleen, tonsil, and thymus. Runts also exhibited moderate anemia, hypoalbuminemia, and mild hypophosphatemia. Taken together, these findings suggest an association between runting and a chronic stress response (hyperactivity of the hypothalamic-pituitary-adrenal axis).
Pilar Lauzurica - One of the best experts on this subject based on the ideXlab platform.
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proteomics analysis reveals that structural proteins of the virion core and involved in gene expression are the main source for hla class ii ligands in vaccinia virus infected cells
Journal of Proteome Research, 2019Co-Authors: Elena Lorente, Pilar Lauzurica, Eilon Barnea, Alejandro Barriga, Carmen Mir, Mariano Esteban, Antonio J Martingaliano, Concepcion Palomo, Juan Garciaarriaza, Arie AdmonAbstract:Protective cellular and humoral immune responses require previous recognition of viral antigenic peptides complexed with human leukocyte antigen (HLA) class II molecules on the surface of the antigen presenting cells. The HLA class II-restricted immune response is important for the control and the clearance of Poxvirus Infection including vaccinia virus (VACV), the vaccine used in the worldwide eradication of smallpox. In this study, a mass spectrometry analysis was used to identify VACV ligands bound to HLA-DR and -DP class II molecules present on the surface of VACV-infected cells. Twenty-six naturally processed viral ligands among the tens of thousands of cell peptides bound to HLA class II proteins were identified. These viral ligands arose from 19 parental VACV proteins: A4, A5, A18, A35, A38, B5, B13, D1, D5, D7, D12, D13, E3, E8, H5, I2, I3, J2, and K2. The majority of these VACV proteins yielded one HLA ligand and were generated mainly, but not exclusively, by the classical HLA class II antigen processing pathway. Medium-sized and abundant proteins from the virion core and/or involved in the viral gene expression were the major source of VACV ligands bound to HLA-DR and -DP class II molecules. These findings will help to understand the effectiveness of current Poxvirus-based vaccines and will be important in the design of new ones.
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Proteomics Analysis Reveals That Structural Proteins of the Virion Core and Involved in Gene Expression Are the Main Source for HLA Class II Ligands in Vaccinia Virus-Infected Cells
2019Co-Authors: Elena Lorente, Pilar Lauzurica, Antonio J. Martín-galiano, Eilon Barnea, Alejandro Barriga, Concepción Palomo, Juan García-arriaza, Carmen Mir, Mariano Esteban, Arie AdmonAbstract:Protective cellular and humoral immune responses require previous recognition of viral antigenic peptides complexed with human leukocyte antigen (HLA) class II molecules on the surface of the antigen presenting cells. The HLA class II-restricted immune response is important for the control and the clearance of Poxvirus Infection including vaccinia virus (VACV), the vaccine used in the worldwide eradication of smallpox. In this study, a mass spectrometry analysis was used to identify VACV ligands bound to HLA-DR and -DP class II molecules present on the surface of VACV-infected cells. Twenty-six naturally processed viral ligands among the tens of thousands of cell peptides bound to HLA class II proteins were identified. These viral ligands arose from 19 parental VACV proteins: A4, A5, A18, A35, A38, B5, B13, D1, D5, D7, D12, D13, E3, E8, H5, I2, I3, J2, and K2. The majority of these VACV proteins yielded one HLA ligand and were generated mainly, but not exclusively, by the classical HLA class II antigen processing pathway. Medium-sized and abundant proteins from the virion core and/or involved in the viral gene expression were the major source of VACV ligands bound to HLA-DR and -DP class II molecules. These findings will help to understand the effectiveness of current Poxvirus-based vaccines and will be important in the design of new ones
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cd69 deficiency enhances the host response to vaccinia virus Infection through altered nk cell homeostasis
Journal of Virology, 2016Co-Authors: Laura Notario, Elisenda Alaripahissa, Antonio De Molina, Pilar LauzuricaAbstract:UNLABELLED During the host response to viral Infection, the transmembrane CD69 protein is highly upregulated in all immune cells. We have studied the role of CD69 in the murine immune response to vaccinia virus (VACV) Infection, and we report that the absence of CD69 enhances protection against VACV at both short and long times postInfection in immunocompetent and immunodeficient mice. Natural killer (NK) cells were implicated in the increased Infection control, since the differences were greatly diminished when NK cells were depleted. This role of NK cells was not based on an altered NK cell reactivity, since CD69 did not affect the NK cell activation threshold in response to major histocompatibility complex class I NK cell targets or protein kinase C activation. Instead, NK cell numbers were increased in the spleen and peritoneum of CD69-deficient infected mice. That was not just secondary to better Infection control in CD69-deficient mice, since NK cell numbers in the spleens and the blood of uninfected CD69(-/-) mice were already augmented. CD69-deficient NK cells from infected mice did not have an altered proliferation capacity. However, a lower spontaneous cell death rate was observed for CD69(-/-) lymphocytes. Thus, our results suggest that CD69 limits the innate immune response to VACV Infection at least in part through cell homeostatic survival. IMPORTANCE We show that increased natural killer (NK) cell numbers augment the host response and survival after Infection with vaccinia virus. This phenotype is found in the absence of CD69 in immunocompetent and immunodeficient hosts. As part of the innate immune system, NK lymphocytes are activated and participate in the defense against Infection. Several studies have focused on the contribution of NK cells to protection against Infection with vaccinia virus. In this study, it was demonstrated that the augmented early NK cell response in the absence of CD69 is responsible for the increased protection seen during Infection with vaccinia virus even at late times of Infection. This work indicates that the CD69 molecule may be a target of therapy to augment the response to Poxvirus Infection.
Arie Admon - One of the best experts on this subject based on the ideXlab platform.
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proteomics analysis reveals that structural proteins of the virion core and involved in gene expression are the main source for hla class ii ligands in vaccinia virus infected cells
Journal of Proteome Research, 2019Co-Authors: Elena Lorente, Pilar Lauzurica, Eilon Barnea, Alejandro Barriga, Carmen Mir, Mariano Esteban, Antonio J Martingaliano, Concepcion Palomo, Juan Garciaarriaza, Arie AdmonAbstract:Protective cellular and humoral immune responses require previous recognition of viral antigenic peptides complexed with human leukocyte antigen (HLA) class II molecules on the surface of the antigen presenting cells. The HLA class II-restricted immune response is important for the control and the clearance of Poxvirus Infection including vaccinia virus (VACV), the vaccine used in the worldwide eradication of smallpox. In this study, a mass spectrometry analysis was used to identify VACV ligands bound to HLA-DR and -DP class II molecules present on the surface of VACV-infected cells. Twenty-six naturally processed viral ligands among the tens of thousands of cell peptides bound to HLA class II proteins were identified. These viral ligands arose from 19 parental VACV proteins: A4, A5, A18, A35, A38, B5, B13, D1, D5, D7, D12, D13, E3, E8, H5, I2, I3, J2, and K2. The majority of these VACV proteins yielded one HLA ligand and were generated mainly, but not exclusively, by the classical HLA class II antigen processing pathway. Medium-sized and abundant proteins from the virion core and/or involved in the viral gene expression were the major source of VACV ligands bound to HLA-DR and -DP class II molecules. These findings will help to understand the effectiveness of current Poxvirus-based vaccines and will be important in the design of new ones.
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Proteomics Analysis Reveals That Structural Proteins of the Virion Core and Involved in Gene Expression Are the Main Source for HLA Class II Ligands in Vaccinia Virus-Infected Cells
2019Co-Authors: Elena Lorente, Pilar Lauzurica, Antonio J. Martín-galiano, Eilon Barnea, Alejandro Barriga, Concepción Palomo, Juan García-arriaza, Carmen Mir, Mariano Esteban, Arie AdmonAbstract:Protective cellular and humoral immune responses require previous recognition of viral antigenic peptides complexed with human leukocyte antigen (HLA) class II molecules on the surface of the antigen presenting cells. The HLA class II-restricted immune response is important for the control and the clearance of Poxvirus Infection including vaccinia virus (VACV), the vaccine used in the worldwide eradication of smallpox. In this study, a mass spectrometry analysis was used to identify VACV ligands bound to HLA-DR and -DP class II molecules present on the surface of VACV-infected cells. Twenty-six naturally processed viral ligands among the tens of thousands of cell peptides bound to HLA class II proteins were identified. These viral ligands arose from 19 parental VACV proteins: A4, A5, A18, A35, A38, B5, B13, D1, D5, D7, D12, D13, E3, E8, H5, I2, I3, J2, and K2. The majority of these VACV proteins yielded one HLA ligand and were generated mainly, but not exclusively, by the classical HLA class II antigen processing pathway. Medium-sized and abundant proteins from the virion core and/or involved in the viral gene expression were the major source of VACV ligands bound to HLA-DR and -DP class II molecules. These findings will help to understand the effectiveness of current Poxvirus-based vaccines and will be important in the design of new ones