Project description:Leishmania are medically relevant protozoan parasites that cause leishmaniasis, a neglected tropical disease that can differently manifest depending on the species and the immune status of the host. Previously, it has been suggested that the presence of an endosymbiont double stranded RNA virus, Leishmania RNA Virus 1 (LRV1), within the parasite may leed to an exarcerbation of the disease outcome and represents an important factor for treatment failure and relapse. Here, we provide gene expression data of wild-type (WT) and various knock-out (KO) bone marrow derived macrophages (BMDMs) from mice (C57BL/6) in different conditions of infections and treatments. We included BMDMs from WT, Ifnar-/-, IFNg-/-, iNOs-/-, Nlrx1-/-, Nox2-/- and Prx5-/- mice. BMDMs were either infected with a human protozoan parasite Leishmania guyanensis with or without its endosymbiant dsRNA virus, LRV1 (LgyLRV1+ and LgyLRV1-, respectively). Alternatively BMDMs were treated with poly I:C, a synthetic dsRNA or a TLR2 agonist FSL1 to identify virus dependetn pathways or to explore the impact of co-exposure to additional agents, respectively.
Project description:Leishmania RNA virus 1 (LRV1) is a double stranded RNA (dsRNA) virus found in some strains of the human protozoan parasite Leishmania, the causative agent of leishmaniasis, a neglected tropical disease. Interestingly, the presence of LRV1 inside Leishmania constitutes an important virulence factor which worsens leishmaniasis outcome in a type I interferon (type I IFN) dependent manner and contributes to treatment failure. Understanding how macrophages respond towards Leishmania alone or in combination with LRV1 as well as the role that type I IFNs may play during infection is fundamental to oversee new therapeutic strategies. In order to dissect the macrophage response towards infection, RNA Sequencing (RNA-Seq) was performed on murine wild-type (WT) bone marrow derived macrophages infected with Leishmania guyanensis (Lgy) devoid or not of LRV1 (LgyLRV1- and LgyLRV1+ respectively) or co-infected with LgyLRV1- and Lymphocytic choriomeningitis virus (LCMV) for 8 and 24 hours. Additionally, macrophages were treated with type I IFN (IFNα or IFNβ) after 6 hours of infection.
Project description:We provide gene expression data of wild-type (WT) and various knock-out (KO) bone marrow derived macrophages (BMDMs) from mice (C57BL/6) in different conditions of infections and treatments. We included BMDMs from WT (female and male), Ifnar-/-, IFNg-/-, iNOs-/-, Nlrx1-/- (female and male), Nox2-/- and Prx5-/- mice. BMDMs were either infected with a human protozoan parasite Leishmania guyanensis with or without its endosymbiant double-stranded RNA (dsRNA) virus, Leishmania RNA Virus 1 (LgyLRV1+ and LgyLRV1-, respectively). Alternatively BMDMs were treated with a TLR3 agonist poly I:C, a TLR2 agonist FSL1, with H2O2 or tBHQ.
Project description:Leishmania RNA virus is an endosymbiotic virus of obligate intracellular Leishmania parasites. The presence of Leishmania RNA virus has been associated to metastatic leishmaniasis in hamsters and the failure of the first-line treatment in humans. This experiment aims to find the differences in the microRNA profile of bone-marrow derived macrophages infected with Leishmania RNA virus containing L.guyanensis or virus-free parasites.
Project description:We performed threefold evolution experiment with tobacco etch potyvirus isolate At17b (TEV-At17b) in five different ecotypes of Arabidopsis thaliana L. (Di-2, Ei-2, Ler-0, St-0, and Wt-1,), that are heterogeneous in their susceptibility to TEV-At17b infection. After the evolution phase, (i) we characterized the fitness and virulence of the evolved lineages across all host ecotypes, (ii) the molecular changes fixed in the viral genomes. Next, we analyzed the transcriptoma of the plants using Agilent Microarray tecnology (i)plants infected with local adapted viral lineage, (ii)plants infected with evolved virus vs. ancestal virus, (iii) virus evolved in new host and infecting its original host, (iv) transcriptoma of most specialized and most generalized viruses infecting all five ecotypes.
Project description:Protozoan parasites of the genus Leishmania are the causative agent of leishmaniasis, one of the 13 most important tropical diseases. Leishmania persists as endo-parasite in host macrophages, where it uses multiple strategies to manipulate the microbicidal host cell functions and to escape from the host immune system. Understanding how Leishmania interacts with host macrophages during uptake, differentiation, intracellular replication, and release might be the key to develop new drugs in target-directed approaches to treat patient with leishmaniasis. Short non-coding RNAs are known to regulate the expression of protein-coding genes at post-transcriptional level. Characterization of these processes during Leishmania infection provides deeper insight in the interaction between host and parasites.
Project description:Zika virus (ZIKV) is largely known for causing brain abnormalities due to its ability to infect neural progenitor stem cells (NPC) during early development. Here we show that ZIKV is also capable of infecting and destroying stem-like cancer cells from aggressive human embryonal tumors of the central nervous system (CNS). When evaluating the oncolytic properties of Brazilian Zika virus strain (ZIKVBR) against human breast, prostate, colorectal and embryonal CNS tumor cell lines, a selective infection of CNS tumor cells, followed by a massive necrotic tumor cell death, was verified. Notably, ZIKVBR was more efficient in destroying CNS tumorspheres than normal stem cell neurospheres. A single intracerebroventricular injection of ZIKVBR in BALB/c nude mice bearing orthotopic human embryonal CNS tumor xenografts resulted in a significantly longer survival, reduced tumor burden, fewer metastasis and complete remission in some animals. Tumor cells closely resembling neural stem cells at the molecular level were more susceptible to ZIKVBR oncolytic effects. Altogether, these preclinical findings indicate that ZIKV could be an efficient oncolytic agent to treat aggressive forms of embryonal CNS tumors. Considering the poor effectiveness and severe side effects of available treatments for these tumors and that most ZIKV infections are asymptomatic, our findings open new avenues for novel therapies.
Project description:Autophagy generally participates in innate immunity by elimination of intracellular pathogens. However, many of them developed successful strategies to counteract their autolysosomal digestion and lastly to exploit this catabolic cellular process. Protozoan parasites of the genus Leishmania are the causative agent of leishmaniasis, one of the 13 most important tropical diseases. Leishmania persists as endo-parasite in host macrophages, where it uses multiple strategies to manipulate the microbicidal host cell functions and to escape from the host immune system. Understanding how Leishmania interacts with host macrophages during uptake, differentiation, intracellular replication, and release might be the key to develop new drugs in target-directed approaches to treat patient with leishmaniasis.
Project description:Mandlik2012 - Synthetic circuit of IPC synthase in Leishmania
A genetic circuit for the targeted enzyme inositol phosphorylceramide (IPC) synthase belonging to the protozoan parasite Leishmania
is constructed by Mandlik et al.
(2013).
This model is described in the article:
Synthetic circuit of inositol phosphorylceramide synthase in Leishmania: a chemical biology approach
Mandlik V., Limbachiya D., Shinde S., Mol M, S., Singh, S.
J Chem Biol. January 2013
Abstract:
Building circuits and studying their behavior in cells is a major goal of systems and synthetic biology. Synthetic biology enables the precise control of cellular states for systems studies, the discovery of novel parts, control strategies, and interactions for the design of robust synthetic systems. To the best of our knowledge, there are no literature reports for the synthetic circuit construction for protozoan parasites. This paper describes the construction of genetic circuit for the targeted enzyme inositol phosphorylceramide synthase belonging to the protozoan parasite Leishmania. To explore the dynamic nature of the circuit designed, simulation was done followed by circuit validation by qualitative and quantitative approaches. The genetic circuit designed for inositol phosphorylceramide synthase (Biomodels Database—MODEL1208030000) shows responsiveness, oscillatory and bistable behavior, together with intrinsic robustness.
This model is hosted on BioModels Database
and identified by: MODEL1208030000
.
To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource
for published quantitative kinetic models
.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to the public
domain worldwide. Please refer to CC0 Public Domain
Dedication
for more information.
Project description:To ascertain which genes are involved in pathogenesis of human visceral leishmaniasis (VL) caused by the protozoan parasite Leishmania infantum, we investigated the transcriptional profile of whole blood samples from patients diagnosed with active VL compared to healthy control samples.