Search results for "infektio"

Real-time Fluorescence Measurement of Enterovirus Uncoating

2019

Viruses need to open, i.e., uncoat, in order to release their genomes for efficient replication and translation. Especially for non-enveloped viruses, such as enteroviruses, the cues leading to uncoating are less well known. The status of the virus has previously been observed mainly by transmission electron microscopy using negative staining, cryo electron microscopy, X-ray crystallography or gradient separation (reviewed in Tuthill et al., 2010, Myllynen et al., 2016, Ruokolainen et al., 2019). However, monitoring of uncoating has been limited by the lack of methods detecting dynamic changes of the virions. Here, we present a real-time fluorescence based protocol, which detects the viral …

Outside-host phage therapy as a biological control against environmental infectious diseases

2018

Background Environmentally growing pathogens present an increasing threat for human health, wildlife and food production. Treating the hosts with antibiotics or parasitic bacteriophages fail to eliminate diseases that grow also in the outside-host environment. However, bacteriophages could be utilized to suppress the pathogen population sizes in the outside-host environment in order to prevent disease outbreaks. Here, we introduce a novel epidemiological model to assess how the phage infections of the bacterial pathogens affect epidemiological dynamics of the environmentally growing pathogens. We assess whether the phage therapy in the outside-host environment could be utilized as a biologi…

Functional roles of the membrane-associated AAV protein MAAP

2021

AbstractWith a limited coding capacity of 4.7 kb, adeno-associated virus (AAV) genome has evolved over-lapping genes to maximise the usage of its genome. An example is the recently found ORF in the cap gene, encoding membrane-associated accessory protein (MAAP), located in the same genomic region as the VP1/2 unique domain, but in a different reading frame. This 13 KDa protein, unique to the dependovirus genus, is not homologous to any known protein. Our studies confirm that MAAP translation initiates from the first CTG codon found in the VP1 ORF2. We have further observed MAAP localised in the plasma membrane, in the membranous structures in close proximity to the nucleus and to the nuclea…

Relationship between the endangered freshwater pearl mussel Margaritifera margaritifera, its salmonid host and co-infectants

2018

The relationship between the freshwater pearl mussel (hereafter FPM), Margaritifera margaritifera, and its salmonid host — pivotal for the conservation of this endangered bivalve — is characterized by a long parasitic stage (up to 11 months) and excessive host specificity. This thesis focuses on this relationship by experimentally studying the effect of FPM infection on the growth and resistance of salmonid fish and how the infection influences vulnerability of the host to other parasites and diseases, as well as how exposure of the host to other parasites affects vulnerability to FPM. Infection with FPM results in (i) reduced growth of the host, brown trout, during the parasitic period. Gl…

The influence of infective dose, nutrient availability and coinfection on virulence of Flavobacterium columnare : implications of intensive aquacultu…

2016

Ecological factors are known to affect disease dynamics and even lead to disease emergence. Especially in opportunistic, environmentally transmitted pathogens, the environment may significantly contribute to pathogen virulence. Intensive farming, including aquaculture, has been suggested to create conditions favouring development of highly virulent pathogens. At Finnish fish farms, epidemics caused by opportunistic Flavobacterium columnare have been constantly increasing in their prevalence and severity since the 1980’s. Yet, factors behind the increased virulence of the pathogen and their mechanisms of action have largely remained unsolved. In this thesis, I explore the effects of infectio…

Impact of biotic and abiotic factors on bacterial virulence

2013

Human enterovirus group B viruses rely on vimentin dynamics for efficient processing of viral nonstructural proteins

2020

We report that several viruses from the human enterovirus group B cause massive vimentin rearrangements during lytic infection. Comprehensive studies suggested that viral protein synthesis was triggering the vimentin rearrangements. Blocking the host cell vimentin dynamics with IDPN did not significantly affect the production of progeny viruses and only moderately lowered the synthesis of structural proteins such as VP1. In contrast, the synthesis of the non-structural proteins 2A, 3C, and 3D was drastically lowered. This led to attenuation of the cleavage of the host cell substrates PABP and G3BP1 and reduced caspase activation, thus leading to prolonged cell survival. Furthermore, the loc…

Vemurafenib Inhibits Acute and Chronic Enterovirus Infection by Affecting Cellular Kinase Phosphatidylinositol 4-Kinase Type IIIβ

2023

Enteroviruses are one of the most abundant viruses causing mild to serious acute infections in humans and also contributing to chronic diseases like type 1 diabetes. Presently, there are no approved antiviral drugs against enteroviruses. Here, we studied the potency of vemurafenib, an FDA-approved RAF kinase inhibitor for treating BRAFV600E mutant-related melanoma, as an antiviral against enteroviruses. We showed that vemurafenib prevented enterovirus translation and replication at low micromolar dosage in an RAF/MEK/ERK-independent manner. Vemurafenib was effective against group A, B, and C enteroviruses, as well as rhinovirus, but not parechovirus or more remote viruses such as Semliki Fo…

Slow infection due to lowering amount of intact versus empty particles is a characteristic feature of Coxsackievirus B5, dictated by the structural p…

2019

Enterovirus B species typically cause a rapid cytolytic infection leading to efficient release of progeny viruses. However, they are also capable of persistent infections in tissues, which are suggested to contribute to severe chronic states such as myocardial inflammation and type 1 diabetes. In order to understand the factors contributing to differential infection strategies, we constructed a chimera by combining the capsid proteins from a fast cytolysis causing echovirus 1 (EV1) with non-structural proteins from Coxsackievirus B5 (CVB5) showing persistent infection in RD cells. The results showed that the chimera behaved similar to the parental EV1 leading to efficient cytolysis in both …

Development of novel probes for enterovirus B group to study uncoating and infection

2016

Enterovirus B group (EV-B) viruses are important human pathogens which cause a variety of diseases from mild respiratory illnesses to more severe acute infections such as myocarditis and meningitis. EV-Bs have also been associated with chronic infections and autoimmune diseases such as type I diabetes. Because of their significance, better and more accurate methods are necessary to track and visualize viruses in vitro and in vivo. This thesis focus on the development of novel probes to label viruses site-specifically and track infection in vitro. First, we established a covalent conjugation between gold nanocluster markers and EV-B viruses. We were able to visualize through electron microsc…