Search results for "Host-pathogen interactions"
showing 10 items of 171 documents
Echovirus 1 Entry into Polarized Caco-2 Cells Depends on Dynamin, Cholesterol, and Cellular Factors Associated with Macropinocytosis
2013
ABSTRACT Enteroviruses invade their hosts by crossing the intestinal epithelium. We have examined the mechanism by which echovirus 1 (EV1) enters polarized intestinal epithelial cells (Caco-2). Virus binds to VLA-2 on the apical cell surface and moves rapidly to early endosomes. Using inhibitory drugs, dominant negative mutants, and small interfering RNAs (siRNAs) to block specific endocytic pathways, we found that virus entry requires dynamin GTPase and membrane cholesterol but is independent of both clathrin- and caveolin-mediated endocytosis. Instead, infection requires factors commonly associated with macropinocytosis, including amiloride-sensitive Na + /H + exchange, protein kinase C, …
Within-host evolution decreases virulence in an opportunistic bacterial pathogen
2015
Abstract Background Pathogens evolve in a close antagonistic relationship with their hosts. The conventional theory proposes that evolution of virulence is highly dependent on the efficiency of direct host-to-host transmission. Many opportunistic pathogens, however, are not strictly dependent on the hosts due to their ability to reproduce in the free-living environment. Therefore it is likely that conflicting selection pressures for growth and survival outside versus within the host, rather than transmission potential, shape the evolution of virulence in opportunists. We tested the role of within-host selection in evolution of virulence by letting a pathogen Serratia marcescens db11 sequent…
Slow Infection due to Lowering the Amount of Intact versus Empty Particles Is a Characteristic Feature of Coxsackievirus B5 Dictated by the Structura…
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 fast-cytolysis-causing echovirus 1 (EV1) with nonstructural proteins from coxsackievirus B5 (CVB5), which shows persistent infection in RD cells. The results showed that the chimera behaved similarly to parental EV1, leading to efficient cytolysis in both…
The endocytic trafficking pathway of oncogenic papillomaviruses
2019
Over the last two decades many host cell proteins have been described to be involved in the process of infectious entry of oncogenic human papillomaviruses (HPV). After initial binding and priming of the capsid, a sequence of events on the cell surface precedes the formation of the HPV entry platform. It has been shown that the virus-associated entry complex consists of membrane organizers, tetraspanins CD151 and CD63, and their associated partner proteins such as integrins, growth factor receptors, and the annexin A2 heterotetramer. Further recruitment of cytoplasmic factors such as the obscurin-like protein 1 and actin results in a non-canonical clathrin-independent endocytosis of the vir…
Did the ancient crenarchaeal viruses from the dawn of life survive exceptionally well the eons of meteorite bombardment?
2009
The viruses of Crenarchaeota are unexpectedly diverse in their morphologies, and most have no, or few, genes related to bacterial, eukaryal, euryarchaeal, or other crenarchaeal viruses. Though several different virus morphotypes have been discovered in enrichment cultures of microbial communities collected from geothermally heated environments around the world, the origins of such differences are unknown. We present a model that combines consideration of Earth's geological history, the early emergence of hyperthermophiles, and the early formation of viruses from primordial genes with the intent to explain this vast diversity of crenarchaeal viruses. Several meteorite- or flood basalt-induce…
Intensive fish farming and the evolution of pathogen virulence: the case of columnaris disease in Finland.
2009
Ecological changes affect pathogen epidemiology and evolution and may trigger the emergence of novel diseases. Aquaculture radically alters the ecology of fish and their pathogens. Here we show an increase in the occurrence of the bacterial fish disease Flavobacterium columnare in salmon fingerlings at a fish farm in northern Finland over 23 years. We hypothesize that this emergence was owing to evolutionary changes in bacterial virulence. We base this argument on several observations. First, the emergence was associated with increased severity of symptoms. Second, F. columnare strains vary in virulence, with more lethal strains inducing more severe symptoms prior to death. Third, more vir…
Outside-host growth of pathogens attenuates epidemiological outbreaks.
2012
Opportunist saprotrophic pathogens differ from obligatory pathogens due to their capability in host-independent growth in environmental reservoirs. Thus, the outside-host environment potentially influences host-pathogen dynamics. Despite the socio-economical importance of these pathogens, theory on their dynamics is practically missing. We analyzed a novel epidemiological model that couples outside-host density-dependent growth to host-pathogen dynamics. Parameterization was based on columnaris disease, a major hazard in fresh water fish farms caused by saprotrophic Flavobacterium columnare. Stability analysis and numerical simulations revealed that the outside-host growth maintains high pr…
Open Field Study of Some Zea mays Hybrids, Lipid Compounds and Fumonisins Accumulation
2015
Lipid molecules are increasingly recognized as signals exchanged by organisms interacting in pathogenic and/or symbiotic ways. Some classes of lipids actively determine the fate of the interactions. Host cuticle/cell wall/membrane components such as sphingolipids and oxylipins may contribute to determining the fate of host–pathogen interactions. In the present field study, we considered the relationship between specific sphingolipids and oxylipins of different hybrids of Zea mays and fumonisin by F. verticillioides, sampling ears at different growth stages from early dough to fully ripe. The amount of total and free fumonisin differed significantly between hybrids and increased significantl…
Enhancerless Cytomegalovirus Is Capable of Establishing a Low-Level Maintenance Infection in Severely Immunodeficient Host Tissues but Fails in Expon…
2010
ABSTRACT Major immediate-early transcriptional enhancers are genetic control elements that act, through docking with host transcription factors, as a decisive regulatory unit for efficient initiation of the productive virus cycle. Animal models are required for studying the function of enhancers paradigmatically in host organs. Here, we have sought to quantitatively assess the establishment, maintenance, and level of in vivo growth of enhancerless mutants of murine cytomegalovirus in comparison with those of an enhancer-bearing counterpart in models of the immunocompromised or immunologically immature host. Evidence is presented showing that enhancerless viruses are capable of forming restr…
Impact of Safety-Related Dose Reductions or Discontinuations on Sustained Virologic Response in HCV-Infected Patients: Results from the GUARD-C Cohor…
2015
Background: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the i…