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At least 217 records · Page 12Linked to original sources

PubMed2006

Host life-history strategy explains pathogen-induced sterility.

Virulence is often equated with pathogen-induced mortality, even though loss of fecundity is also common. But while the former may be understood as a simple consequence of lost host resources for the purposes of pathogen transmission, pathogen-induced sterility is often not associated with changes in host mortality. As a result, a separate literature has emerged to explain fecundity effects of parasitism that has not been integrated into general theories of the evolution of virulence. Here, I present a model of pathogen-induced sterility that is based on the assumption that hosts and pathogens vie for the same host resources for both reproduction and maintenance. Loss of host fecundity can then be explained by the host compensating for its future loss of resources, before infection. Such preinfection ;;fecundity compensation" may often cause preinfection investment in maintenance to be as low as postinfection levels, despite a loss of total host resources after infection. Thus, sterility is simply explained as a host life-history strategy in a system where the pathogen necessarily steals host resources for its own transmission. In certain circumstances, the pathogen may even be able to manipulate the host to redirect resources away from reproduction and toward maintenance through castration, causing gigantism.

Animals↗

PubMed2002

The chlamydial inclusion: escape from the endocytic pathway.

Chlamydiae, bacterial obligate intracellular pathogens, are the etiologic agents of several human diseases. A large part of the chlamydial intracellular survival strategy involves the formation of a unique organelle called the inclusion that provides a protected site within which they replicate. The chlamydial inclusion is effectively isolated from endocytic pathways but is fusogenic with a subset of exocytic vesicles that deliver sphingomyelin from the Golgi apparatus to the plasma membrane. A combination of host and parasite functions contribute to the biogenesis of this compartment. Establishment of the mature inclusion is accompanied by the insertion of multiple chlamydial proteins, suggesting that chlamydiae actively modify the inclusion to define its interactions with the eukaryotic host cell. Despite being sequestered within a membrane-bound vacuole, chlamydiae clearly communicate with and manipulate the host cell from within this privileged intracellular niche.

Animals↗

PubMed2004

Wolbachia replication and host cell division in Aedes albopictus.

Wolbachia pipientis is an obligate intracellular endosymbiont of a range of arthropod species. The microbe is best known for its manipulations of host reproduction that include inducing cytoplasmic incompatibility, parthenogenesis, feminization, and male-killing. Like other vertically transmitted intracellular symbionts, Wolbachia's replication rate must not outpace that of its host cells if it is to remain benign. The mosquito Aedes albopictus is naturally infected both singly and doubly with different strains of Wolbachia pipientis. During diapause in mosquito eggs, no host cell division is believed to occur. Further development is triggered only by subsequent exposure of the egg to water. This study uses diapause in Wolbachia-infected Aedes albopictus eggs to determine whether symbiont replication slows or stops when host cell division ceases or whether it continues at a low but constant rate. We have shown that Wolbachia densities in eggs are greatest during embryonation and then decline throughout diapause, suggesting that Wolbachia replication is dependent on host cell replication.

Aedes↗

PubMed2004

African swine fever virus proteins involved in evading host defence systems.

African swine fever virus (ASFV) can cause an acutely fatal haemorrhagic fever in domestic pigs although in its natural hosts, warthogs, bushpigs and the soft tick vector, Ornithodoros moubata, ASFV causes inapparent persistent infections. The virus is a large, cytoplasmic, double-stranded DNA virus which has a tropism for macrophages. As it is the only member of the Asfarviridae family, ASFV encodes many novel genes not encoded by other virus families. The ability of the virus to persist in its natural hosts and in domestic pigs, which recover from infection with less virulent isolates, shows that the virus has effective mechanisms to evade host defence systems. This review focuses on recent progress made in understanding the function of ASFV-encoded proteins, which are involved in modulating the host response to infection. Growing evidence suggests that a major strategy used by the virus is to modulate signalling pathways in infected macrophages, thus interfering with the expression of a large number of immunomodulatory genes. One potent immunomodulatory protein, A238L, inhibits both activation of the host NFkappaB transcription factor and inhibits calcineurin phosphatase activity. Calcineurin-dependent pathways, including activation of the NFAT transcription factor, are therefore inhibited. Another ASFV-encoded protein, CD2v, resembles the host CD2 protein, which is expressed on T cells and NK cells. This virus protein causes the adsorption of red blood cells around virus-infected cells and extracellular virus particles. Expression of the CD2v protein aids virus dissemination in pigs and the protein also has a role in impairing bystander lymphocyte function. This may be mediated either by a direct interaction of CD2v extracellular domain with ligands on lymphocytes or by an indirect mechanism involving interaction of the CD2v cytoplasmic tail with host proteins involved in signalling or trafficking pathways. Two ASFV proteins, an IAP and a Bcl2 homologue, inhibit apoptosis in infected cells and thus facilitate production of progeny virions. The prediction is that half to two-thirds of the approximately 150 genes encoded by ASFV are not essential for replication in cells but have an important role for virus survival and transmission in its hosts. These genes provide an untapped repository, and will be valuable tools for deciphering not only how the virus manipulates the host response to infection to avoid elimination, but also useful for understanding important host anti-viral mechanisms. In addition, they may provide leads for discovery of novel immunomodulatory drugs.

Adjuvants, Immunologic↗

PubMed2006

Gene expression profiling of Spodoptera frugiperda hemocytes and fat body using cDNA microarray reveals polydnavirus-associated variations in lepidopteran host genes transcript levels.

BACKGROUND: Genomic approaches provide unique opportunities to study interactions of insects with their pathogens. We developed a cDNA microarray to analyze the gene transcription profile of the lepidopteran pest Spodoptera frugiperda in response to injection of the polydnavirus HdIV associated with the ichneumonid wasp Hyposoter didymator. Polydnaviruses are associated with parasitic ichneumonoid wasps and are required for their development within the lepidopteran host, in which they act as potent immunosuppressive pathogens. In this study, we analyzed transcriptional variations in the two main effectors of the insect immune response, the hemocytes and the fat body, after injection of filter-purified HdIV. RESULTS: Results show that 24 hours post-injection, about 4% of the 1750 arrayed host genes display changes in their transcript levels with a large proportion (76%) showing a decrease. As a comparison, in S. frugiperda fat body, after injection of the pathogenic JcDNV densovirus, 8 genes display significant changes in their transcript level. They differ from the 7 affected by HdIV and, as opposed to HdIV injection, are all up-regulated. Interestingly, several of the genes that are modulated by HdIV injection have been shown to be involved in lepidopteran innate immunity. Levels of transcripts related to calreticulin, prophenoloxidase-activating enzyme, immulectin-2 and a novel lepidopteran scavenger receptor are decreased in hemocytes of HdIV-injected caterpillars. This was confirmed by quantitative RT-PCR analysis but not observed after injection of heat-inactivated HdIV. Conversely, an increased level of transcripts was found for a galactose-binding lectin and, surprisingly, for the prophenoloxidase subunits. The results obtained suggest that HdIV injection affects transcript levels of genes encoding different components of the host immune response (non-self recognition, humoral and cellular responses). CONCLUSION: This analysis of the host-polydnavirus interactions by a microarray approach indicates that the presence of HdIV induces, directly or indirectly, variations in transcript levels of specific host genes, changes that could be responsible in part for the alterations observed in the parasitized host physiology. Development of such global approaches will allow a better understanding of the strategies employed by parasites to manipulate their host physiology, and will permit the identification of potential targets of the immunosuppressive polydnaviruses.

Animals↗

PubMed1988

Selection of antibody repertoires by anti-idiotypes can occur at multiple steps of B cell differentiation.

These experiments were designed to evaluate whether alterations in Id expression after anti-Id treatments result from direct modulation of Id-producing B cells, and whether idiotypic selection operates in bone marrow or spleen B cells. By using the NPb Id model, we have studied the functional behavior of isolated LPS-reactive B cells transferred from B6 mice into histocompatible LPS-NR B10.Cr hosts and primed with LPS conjugates of anti-Id antibodies. We have found that previous anti-idiotypic manipulation of host mice by neonatal administration of suppressive doses of Ac 38 antibodies, or adult injection of enhancing doses of Ac 146 antibodies, modulated the T cell-independent Id response of either immature bone marrow or mature splenic responding cells, transferred from normal, untreated donors. These results are interpreted to suggest that selection of antibody repertoires by anti-Id may occur at multiple steps of B cell differentiation.

Animals↗

PubMed2005

Solving a sticky problem: new genetic approaches to host cell adhesion by the Lyme disease spirochete.

The Lyme disease spirochetes, comprised of at least three closely related species, Borrelia burgdorferi, Borrelia garinii and Borrelia afzelii, are fascinating and enigmatic bacterial pathogens. They are maintained by tick-mediated transmission between mammalian hosts, usually small rodents. The ability of these bacteria, which have relatively small genomes, to survive and disseminate in both an immunocompetent mammal and in an arthropod vector suggests that they have evolved elegant and indispensable strategies for interacting with their hosts. Recognition of specific mammalian and tick tissues is likely to be essential for successful completion of the enzootic life cycle but, given the historical difficulties in genetic manipulation of these organisms, characterization of factors promoting cell adhesion has until recently largely been confined to either the manipulation of host cells or the analysis of potential bacterial ligands in the form of recombinant proteins. These studies have led to the identification of several mammalian receptors for Lyme disease spirochetes, including glycosaminoglycans, decorin, fibronectin and integrins, as well as a tick receptor for the bacterium, and also candidate cognate bacterial ligands. Recent advances in our ability to genetically manipulate Lyme disease spirochetes, particularly B. burgdorferi, are now providing us with firm evidence that these ligands indeed do promote bacterial adherence to host cells, and with new insights into the roles of these multifacted Borrelia-host cell interactions during mammalian and arthropod infection.

Animals↗

PubMed2001

Parasites and supernormal manipulation.

Social parasites may exploit their hosts by mimicking other organisms that the hosts normally benefit from investing in or responding to in some other way. Some parasites exaggerate key characters of the organisms they mimic, possibly in order to increase the response from the hosts. The huge gape and extreme begging intensity of the parasitic common cuckoo chick (Cuculus canorus) may be an example. In this paper, the evolutionary stability of manipulating hosts through exaggerated signals is analysed using game theory. Our model indicates that a parasite's signal intensity must be below a certain threshold in order to ensure acceptance and that this threshold depends directly on the rate of parasitism. The only evolutionarily stable strategy (ESS) combination is when hosts accept all signallers and parasites signal at their optimal signal intensity, which must be below the threshold. Supernormal manipulation by parasites is only evolutionarily stable under sufficiently low rates of parasitism. If the conditions for the ESS combination are not satisfied, rejector hosts can invade using signal intensity as a cue for identifying parasites. These qualitative predictions are discussed with respect to empirical evidence from parasitic mimicry systems that have been suggested to involve supernormal signalling, including evicting avian brood parasites and insect-mimicking Ophrys orchids.

Adaptation, Physiological↗

PubMed2004

Molecular modifications of host cells by Toxoplasma gondii.

Toxoplasma gondii, the etiological agent of toxoplasmosis, is an Apicomplexa obligate intracellular protozoan parasite, which is able to infect any nucleated cell of numerous endothermic vertebrates. The combined abilities to actively penetrate host cells and perfectly control the fate of the parasite-containing vacuole (parasitophorus vacuole, PV) contribute to the remarkable global success of Toxoplasma as an intracellular parasite. Very broad host range and the relative ease of growth both in cell cultures in vitro and in vivo suggest that the parasite is able to manipulate the host cell apoptotic machinery. The article describes different aspects of host-parasite interplay focusing on molecular modifications of infected host cells.

Animals↗

PubMed2001

Unexpected anthropophagic behaviour in Anopheles quadriannulatus.

The strongly anthropophilic behaviour of Anopheles gambiae Giles sensu stricto (Diptera: Culicidae), the most important malaria vector in Africa, has been demonstrated by field and laboratory studies. Other members of the An. gambiae complex express varied degrees of anthropophily. Anopheles quadriannulatus (Theobald) species A and B are more zoophilic members of the complex and hence are considered to be of no medical importance. Olfactometer experiments with An. quadriannulatus species A have demonstrated attraction to both human and cow odour. To extend these olfactometer observations a choice experiment was conducted in an outdoor cage with a human and a calf as baits, using laboratory-reared mosquitoes. Anopheles gambiae s.s. (from Liberia) and two strains of An. quadriannulatus species A (SKUQUA from South Africa, SANGQUA from Zimbabwe), marked with different coloured fluorescent powders for identification purposes, were released simultaneously and given an equal opportunity to feed on either host. The experiment was repeated six times. Bloodmeals were identified using the precipitin technique. Anopheles gambiae s.s. showed highly anthropophagic behaviour, taking 88% of bloodmeals from the human host. In contrast, both strains of An. quadriannulatus fed with equal frequency on the human or the calf; the response to either host was not significantly different. These results confirm the olfactometer findings and demonstrate anthropophagic behaviour not previously recorded in this species. This finding has implications for prospective manipulation of host preference for genetic control purposes.

Animals↗

PubMed2001

Genetic structure in natural populations of flukes and snails: a practical approach and review.

Several aspects of the coevolutionary dynamics in host-parasite systems may be better quantified based on analyses of population structure using neutral genetic markers. This includes, for example, the migration rates of hosts and parasites. In this respect, the current situation, especially in fluke-snail systems is unsatisfactory, since basic population genetics data are lacking and the appropriate methodology has rarely been used. After reviewing the forces acting on population structure (e.g. genetic drift or the mating system) and how they can be analysed in models of structured populations, we propose a simplified, indicative framework for conducting analyses of population structure in hosts and parasites. This includes consideration of markers, sampling, data analysis, comparison of structure in hosts and parasites and use of external data (e.g. from population dynamics). We then focus on flukes and snails, highlighting important biological traits with regard to population structure. The few available studies indicate that asexual amplification of flukes within snails strongly influences adult flukes populations. They also show that the genetic structure among populations in strongly affected by traits in other than snails (e.g. definitive host dispersal behaviour), as snails populations have limited migration. Finally more studies would allow us to deepen our current understanding of selective interference between flukes and snails (e.g. manipulation of host mating system by parasites), and evaluate how this affect population structure at neutral markers.

Animals↗

PubMed2005

Bacterial toxins that modulate host cell-cycle progression.

The mammalian cell cycle is involved in many processes--such as immune responses, maintenance of epithelial barrier functions, and cellular differentiation--that affect the growth and colonization of pathogenic bacteria. Therefore it is not surprising that many bacterial pathogens manipulate the host cell cycle with respect to these functions. Cyclomodulins are a growing family of bacterial toxins and effectors that interfere with the eukaryotic cell cycle. Here, we review some of these cyclomodulins such as cytolethal distending toxins, vacuolating cytotoxin, the polyketide-derived macrolide mycolactone, cycle-inhibiting factor, cytotoxic necrotizing factors, dermonecrotic toxin, Pasteurella multocida toxin and cytotoxin-associated antigen A. We describe and compare their effects on the mammalian cell cycle and their putative role in disease, commensalism and symbiosis. We also discuss a possible link between these cyclomodulins and cancer.

Animals↗

PubMed2002

The injured brain interacts reciprocally with neural stem cells supported by scaffolds to reconstitute lost tissue.

Hypoxic-ischemic injury is a prototype for insults characterized by extensive tissue loss. Seeding neural stem cells (NSCs) onto a polymer scaffold that was subsequently implanted into the infarction cavities of mouse brains injured by hypoxia-ischemia allowed us to observe the multiple reciprocal interactions that spontaneously ensue between NSCs and the extensively damaged brain: parenchymal loss was dramatically reduced, an intricate meshwork of many highly arborized neurites of both host- and donor-derived neurons emerged, and some anatomical connections appeared to be reconstituted. The NSC-scaffold complex altered the trajectory and complexity of host cortical neurites. Reciprocally, donor-derived neurons were seemingly capable of directed, target-appropriate neurite outgrowth (extending axons to the opposite hemisphere) without specific external instruction, induction, or genetic manipulation of host brain or donor cells. These "biobridges" appeared to unveil or augment a constitutive reparative response by facilitating a series of reciprocal interactions between NSC and host, including promoting neuronal differentiation, enhancing the elaboration of neural processes, fostering the re-formation of cortical tissue, and promoting connectivity. Inflammation and scarring were also reduced, facilitating reconstitution.

Animals↗

PubMed2002

Cell signalling and Trypanosoma cruzi invasion.

Mammalian cell invasion by the protozoan pathogen Trypanosoma cruzi is critical to its survival in the host. To promote its entry into a wide variety of non-professional phagocytic cells, infective trypomastigotes exploit an arsenal of heterogenous surface glycoproteins, secreted proteases and signalling agonists to actively manipulate multiple host cell signalling pathways. Signals initiated in the parasite upon contact with mammalian cells also function as critical regulators of the invasion process. Whereas the full spectrum of cellular responses modulated by T. cruzi is not yet known, mounting evidence suggests that these pathways impinge on a number of cellular processes, in particular the ubiquitous wound-repair mechanism exploited for lysosome-mediated parasite entry. Furthermore, differential engagement of host cell signalling pathways in a cell type-specific manner and modulation of host cell gene expression by T. cruzi are becoming recognized as essential determinants of infectivity and intracellular survival by this pathogen.

Animals↗

PubMed2005

Kaposi's sarcoma-associated herpesvirus modulates microtubule dynamics via RhoA-GTP-diaphanous 2 signaling and utilizes the dynein motors to deliver its DNA to the nucleus.

Human herpesvirus 8 (HHV-8; also called Kaposi's sarcoma-associated herpesvirus), which is implicated in the pathogenesis of Kaposi's sarcoma (KS) and lymphoproliferative disorders, infects a variety of target cells both in vivo and in vitro. HHV-8 binds to several in vitro target cells via cell surface heparan sulfate and utilizes the alpha3beta1 integrin as one of its entry receptors. Interactions with cell surface molecules induce the activation of host cell signaling cascades and cytoskeletal changes (P. P. Naranatt, S. M. Akula, C. A. Zien, H. H. Krishnan, and B. Chandran, J. Virol. 77:1524-1539, 2003). However, the mechanism by which the HHV-8-induced signaling pathway facilitates the complex events associated with the internalization and nuclear trafficking of internalized viral DNA is as yet undefined. Here we examined the role of HHV-8-induced cytoskeletal dynamics in the infectious process and their interlinkage with signaling pathways. The depolymerization of microtubules did not affect HHV-8 binding and internalization, but it inhibited the nuclear delivery of viral DNA and infection. In contrast, the depolymerization of actin microfilaments did not have any effect on virus binding, entry, nuclear delivery, or infection. Early during infection, HHV-8 induced the acetylation of microtubules and the activation of the RhoA and Rac1 GTPases. The inactivation of Rho GTPases by Clostridium difficile toxin B significantly reduced microtubular acetylation and the delivery of viral DNA to the nucleus. In contrast, the activation of Rho GTPases by Escherichia coli cytotoxic necrotizing factor significantly augmented the nuclear delivery of viral DNA. Among the Rho GTPase-induced downstream effector molecules known to stabilize the microtubules, the activation of RhoA-GTP-dependent diaphanous 2 was observed, with no significant activation in the Rac- and Cdc42-dependent PAK1/2 and stathmin molecules. The nuclear delivery of viral DNA increased in cells expressing a constitutively active RhoA mutant and decreased in cells expressing a dominant-negative mutant of RhoA. HHV-8 capsids colocalized with the microtubules, as observed by confocal microscopic examination, and the colocalization was abolished by the destabilization of microtubules with nocodazole and by the phosphatidylinositol 3-kinase inhibitor affecting the Rho GTPases. These results suggest that HHV-8 induces Rho GTPases, and in doing so, modulates microtubules and promotes the trafficking of viral capsids and the establishment of infection. This is the first demonstration of virus-induced host cell signaling pathways in the modulation of microtubule dynamics and in the trafficking of viral DNA to the infected cell nucleus. These results further support our hypothesis that HHV-8 manipulates the host cell signaling pathway to create an appropriate intracellular environment that is conducive to the establishment of a successful infection.

Acetylation↗

PubMed2005

Early and sustained expression of latent and host modulating genes in coordinated transcriptional program of KSHV productive primary infection of human primary endothelial cells.

Coordinated expression of viral genes in primary infection is essential for successful infection of host cells. We examined the expression profiles of Kaposi's sarcoma-associated herpesvirus (KSHV) transcripts in productive primary infection of primary human umbilical vein endothelial cells by whole-genome reverse-transcription real-time quantitative PCR. The latent transcripts were expressed early and sustained at high levels throughout the infection while the lytic transcripts were expressed in the order of immediate early, early, and lytic transcripts, all of which culminated before the production of infectious virions. Significantly, transcripts encoding genes with host modulating functions, including mitogenic and cell cycle-regulatory, immune-modulating, and anti-apoptotic genes, were expressed before those encoding viral structure and replication genes, and sustained at high levels throughout the infection, suggesting KSHV manipulation of host environment to facilitate infection. The KSHV transcriptional program in a primary infection defined in this study should provide a basis for further investigation of virus-cell interactions.

Apoptosis↗

PubMed2005

Role of protein phosphorylation on serine/threonine and tyrosine in the virulence of bacterial pathogens.

Bacterial pathogens have developed a diversity of strategies to interact with host cells, manipulate their behaviors, and thus to survive and propagate. During the process of pathogenesis, phosphorylation of proteins on hydroxyl amino acids (serine, threonine, tyrosine) occurs at different stages, including cell-cell interaction and adherence, translocation of bacterial effectors into host cells, and changes in host cellular structure and function induced by infection. The phosphorylation reactions are catalyzed in a reversible fashion by specific protein kinases and phosphatases that belong to either the invading bacterial cells or the infected eukaryotic host cells. Among the various virulence factors involved in bacterial pathogenesis, special attention has been paid recently to the cell wall components, exopolysaccharides. A major breakthrough has been made by showing the existence of a biological link between the activity of certain protein-tyrosine kinases/phosphatases and the production and/or transport of surface polysaccharides. In addition, genetic studies have revealed a key role played by some serine/threonine kinases in pathogenesis. Considering the structural organization and membrane topology of these different kinases, it can be envisaged that they operate as one-component systems in signal transduction pathways, in the form of single proteins containing input and output domains on the same polypeptide chain. From a general standpoint, the demonstration of a direct relationship between protein phosphorylation on serine/threonine/tyrosine and bacterial virulence represents a novel concept of great importance in deciphering the molecular and cellular mechanisms that underlie pathogenesis.

Adaptation, Physiological↗

PubMed1999

Molecular domestication--more than a sporadic episode in evolution.

Transposable elements are short but complex pieces of DNA or RNA containing a streamlined minimal-genome with the capacity for its selfish replication in a foreign genomic environment. Cis-regulatory sections within the elements orchestrate tempo and mode of TE expression. Proteins encoded by TEs mainly direct their own propagation within the genome by recruitment of host-encoded factors. On the other hand, TE-encoded proteins harbor a very attractive repertoire of functional abilities for a cell. These proteins mediate excision, replication and integration of defined DNA fragments. Furthermore, some of these proteins are able to manipulate important host factors by altering their original function. Thus, if the host genome succeeds in domesticating such TE-encoded proteins by taming their 'anarchistic behavior,' such an event can be considered as an important evolutionary innovation for its own benefit. In fact, the domestication of TE-derived cis-regulatory modules and protein coding sections took place repeatedly in the course of genome evolution. We will present prominent cases that impressively demonstrate the beneficial impact of TEs on host biology over evolutionary time. Furthermore, we will propose that molecular domestication might be considered as a resumption of the same evolutionary process that drove the transition from 'primitive genomes' to 'modern' ones at the early dawn of life, that is, the adaptive integration of a short piece of autonomous DNA into a complex regulatory network.

Amino Acid Sequence↗