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The role of IFI16 protein in viral infection
Karchňák, Jan ; Šroller, Vojtěch (advisor) ; Poláková, Ingrid (referee)
6 Abstract Viruses are obligate intracellular parasites causing a large variety of diseases. Most of their hosts, including humans, have developed particular mechanisms, which are meant to tackle such diseases. First line of defense against viruses are pattern recognition receptors. These receptors are responsible for detection of pathogen associated molecular patterns (PAMPs) and of damage associated molecular patterns (DAMPs). Inteferon γ inducible protein 16 (IFI16) is one of these receptors and is responsible for detecting alien and damaged DNA both in the nucleus and cytoplasm. Its structure contains two sequence independent DNA binding HIN domains and one PYD domain, which mediates its protein-protein interactions. In the cell it functions as a regulator of cell cycle, differentiation and plays a role in cell aging. IFI16 also triggers activation of non-specific immune response and it directly acts as a restrictive factor for many viruses. During evolution these viruses have evolved mechanism which they us to evade its imunne activity or even use it to their advantage. Keywords: IFI16, STING, DNA sensing, interferons, restriction factor, pattern recogniton receptors
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Molecular Factors of Cell Antiviral Immunity
SELINGER, Martin
The proposed thesis focuses on the description of flavivirus-host interactions in case of tick-borne encephalitis virus (TBEV) and Zika virus (ZIKV). In more detail, the TBEV-induced host responses in human cells of neural origin and interferon-mediated protection were described together with the identification of a new phenomenon of TBEV-induced host transcriptional and translational shut-off. In addition, virus-derived molecules with hypothetical immunomodulatory characteristics, TuORF and ZIKV sfRNA, were analysed for their presence and possible function during the infection.
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Negative regulation of the IFI16 and cGAS DNA sensing pathways
Muhič, Samra ; Huerfano Meneses, Sandra (advisor) ; Kanwal, Madiha (referee)
DNA sensors are molecules with the ability to sense DNA constituting an important tool of innate immunity. They are initiators of various signalling pathways, one of them being the production of interferons, which induce not only an anti-viral cell state but also protect cells of treats not related to pathogens. At least, fourteen DNA sensors have been described so far, among them - IFI16 and cGAS. Both sensors signal via an adaptor protein STING resulting in the production of type I IFN. All three of these molecules (cGAS, IFI16, STING) are strictly regulated either by host-cells in order to prevent immune over-activation or by viruses for the immune evasion. This work focuses on the mechanisms of negative regulation of the three molecules: post-translational modifications such as phosphorylation, ubiquitination, SUMOylation, acetylation and methylation; protein-protein interactions; degradation by the proteasomal system or by autophagy. Not surprisingly, viruses encode proteins able to down-regulate IFN responses for example, some proteins of herpes viruses interact with cGAS, IFI16 or STING preventing their activation or leading to their degradation. Other proteins of herpes viruses cause the degradation of the mRNA of the sensors or the adaptor. Dengue protease factor NS2B degrades cGAS or the...
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POSITIVE AND NEGATIVE HOST FACTORS OF AVIAN SARCOMA AND LEUKOSIS VIRUSES
Krchlíková, Veronika ; Elleder, Daniel (advisor) ; Růžek, Daniel (referee) ; Španielová, Hana (referee)
Identification and characterization of the host cell factors that either support or inhibit virus replication constitutes a major direction in virological research. In this work we focus on several such host factors in the context of avian cell. Chicken Tva, cell entry receptor for subgroups A and K of Avian sarcoma and leukosis virus (ASLV), was identified to be orthologous to human receptor for cellular uptake of cobalamin (Cbl). Here, we describe Cbl uptake in chicken cells and its dependency on Tva. Additionally, we characterize in vivo Tva knockout in chicken. Chicken Tvb receptor conferring susceptibility to subgroups B, D and E of ASLV was previously shown to participate in virus-induced cytopathic effects. In this work, we identify a natural ligand of Tvb and investigate its participation in apoptosis. RIG-I-like receptors (RLR) are a key family of cytosolic viral RNA sensors. The activation of these receptors leads to establishment of an antiviral state in the cell. In this study, we describe repeated evolutionary losses of RLR genes in birds: the loss of MDA5 in two avian orders and the loss of RIG-I in multiple species. Tetherin is an antiviral restriction factor blocking the release of newly formed viral particles. We identify tetherin orthologs in avian species and investigate...
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The role of Interferon regulatory factors in virus infections
Suchý, Tomáš ; Forstová, Jitka (advisor) ; Matyska Lišková, Petra (referee)
Viruses are intracellular parasites, which expose their proteins and nucleic acids during their interaction with a cell. Thanks to co-evolution the host immune system developed mechanims how to recognize these components and subsequently activate defensive mechanisms. This work summarizes the knowledge about selected transcription factors with interferon regulatory function. Induction of the antiviral state is complicated and strictly regulated process. Primary function of selected transcription factors is to connect virus detection and synthesis of cellular molecules with antiviral potential. The work includes information about the direct interaction of viral proteins with interferon regulatory factors. These facts enable us insight into the molecular struggle between a host and a virus. As the name of factors suggests, the most important function is to influence the interferon production. Gathering of information about coordination of the immune system is beneficial for humane medicine and future therapeutic purposes. Key words: interferon regulatory factors; viral infection; regulation of innate immunity; interferon; pathogen recognition
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Laboratory diagnosis of tuberculosis based on Interferon-Gamma Release Assay (IGRA)
BEDNÁŘOVÁ, Marcela
Interferon-gamma release assay (IGRA) methods have become a common part of the routine tuberculosis (TB) diagnosis. These are indirect diagnostic methods, which detect the cell-mediated immune reactivity to the presence of Mycobacterium tuberculosis antigens inside the human body. The methods are based on the principle of detection of interferon-gama(IFN-gama) produced by the T-lymphocytes sensitized by TB antigens. Currently, there are two tests available (QuantiFERON -TB Gold In -Tube and T - SPOT.TB). This thesis is dealing with the principle, the practical use and the place of IGRA methods in the comprehensive diagnosis of TB. The Collection of 1554 blood samples, examined by QuantiFERON-TB Gold In-Tube in the period from 1st June 2011 to 30th June 2013 in the Mycobacteriology Laboratory of the University Hospital in Pilsen was evaluated in the practical part. The percentage of various types of health care settings indicating this examination, as well as the percentage of positive, negative and undetermined results in some selected groups of patients (screening before the initiation of biological treatment, in patients with primary lung tumors, in person with a high-risk of TB and person in contact with active form of the disease) was monitored. The results of patients with active TB verified by culture were also assessed. The results of this study indicated, that IGRA methods are of a great contribution in the TB diagnosis, in particular in the latent form, under certain conditions also in the active form. At the same time it should bementioned, that the diagnosis of tuberculosis must always be complex. This method should not be used for the TB diagnosis solely.
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