Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “virulence evolution”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 919 records · Page 51Linked to original sources
PubMed1992

Cloning and sequence analysis of the genes encoding the nonstructural proteins of Langat virus and comparative analysis with other flaviviruses.

Langat virus, a member of the family Flaviviridae is antigenically very similar to highly pathogenic tick-borne encephalitis viruses. We cloned and sequenced the complete nonstructural gene-coding region of Langat virus (strain TP21) and compared the deduced amino acid sequences of each nonstructural protein to those of other flaviviruses. By alignment with the reported amino acid sequences of the nonstructural proteins of several flaviviruses, we were able to predict proteolytic cleavage sites and identify sequence motifs, which are highly conserved among flaviviruses. Sequence similarity calculations revealed that the NS3 and NS5 proteins are the most highly conserved of the flavivirus nonstructural proteins. The NS3 and NS5 proteins of Langat virus contained specific peptide sequences that have been demonstrated to be associated with helicase or polymerase activities, respectively. The NS1 protein of Langat virus displayed complete homology of potential N-linked glycosylation sites and cysteine residues with the NS1 proteins of other tick-borne flaviviruses, suggesting a highly conserved NS1 protein structure. The data presented in this report serve to complete the entire sequence of the Langat virus-coding region and provide the basis for comparison of this naturally attenuated virus to the other highly virulent tick-borne flaviviruses.

Amino Acid Sequence↗
PubMed1998

Complexity of trypanosomatid endocytosis pathways revealed by Rab4 and Rab5 isoforms in Trypanosoma brucei.

Small G proteins of the Rab family are responsible for vesicle fusion and control flux during intracellular transport. Rab5 is important in endosome maturation and Rab4 in recycling of endocytic material. Three Rab5 isoforms identified so far in mammals and three in the yeast genome suggest that conservation of multiple Rab5 isoforms is required for sophisticated regulation of endocytosis. Trypanosoma brucei homologues of Rab5 and Rab4 (TbRab5A and TbRab4) have been identified. Here we report cloning of a second Rab5 homologue, TbRab5Bp. The TbRAB5A and -5B genes are not linked in the genome, and phylogenetic reconstruction indicates that multiple Rab5 isoforms in yeast, mammals, and trypanosomes evolved independently. Northern blots demonstrate that TbRab5A, -5B, and TbRab4 messages are expressed in bloodstream form (BSF) and procyclic forms of the parasite even though endocytosis is not very active in the latter form. mRNA levels of TbRab5A and -4 are constitutive. Multiple-sized TbRab5B messages at very low abundance are detected, with greater expression in BSF. Also, the TbRab5B mRNA has a large 3'-untranslated region suggestive of potentially complex regulation, and therefore TbRab5Bp may be an important regulator of differential endocytosis levels between BSF and procyclic stage parasites. Affinity purified antibodies raised to C-terminal peptide sequences of all three TbRab proteins recognized small vesicular cytoplasmic structures, which for TbRab5Ap and -5Bp are predominantly near the flagellar pocket. TbRab5Bp colocalizes with invariant surface glycoprotein 100 (ISG100), a protein entering the endocytotic pathway in BSF parasites, whereas in procyclic cells populations of vesicles stained with both TbRab5Ap and -5Bp substantially overlap; TbRab5 proteins are therefore components of the endocytotic pathway. TbRab4p localizes to vesicular structures throughout the cytoplasm, with some overlap with TbRab5Bp, but the majority occupying a different compartment to the TbRab5s. Therefore the trypanosome endosomal system has been functionally dissected for the first time; these reagents provide a unique opportunity for manipulation of the protozoan endosomal system to further our understanding of drug uptake mechanisms and virulence.

Amino Acid Sequence↗
PubMed1996

Repeated transfer of small RNA virus populations leading to balanced fitness with infrequent stochastic drift.

The population dynamics of RNA viruses have an important influence on fitness variation and, in consequence, on the adaptative potential and virulence of this ubiquitous group of pathogens. Earlier work with vesicular stomatitis virus showed that large population transfers were reproducibly associated with fitness increases, whereas repeated transfers from plaque to plaque (genetic bottlenecks) lead to losses in fitness. We demonstrate here that repeated five-plaque to five-plaque passage series yield long-term fitness stability, except for occasional stochastic fitness jumps. Repeated five-plaque passages regularly alternating with two consecutive large population transmissions did not cause fitness losses, but did limit the size of fitness gains that would otherwise have occurred. These results underscore the profound effects of bottleneck transmissions in virus evolution.

Animals↗
PubMed2005

Venezuelan equine encephalitis virus in the guinea pig model: evidence for epizootic virulence determinants outside the E2 envelope glycoprotein gene.

Epizootic strains of Venezuelan equine encephalitis virus (VEEV) cause epidemics by exploiting equines as highly efficient amplification hosts for mosquito transmission. Although phylogenetic studies indicate that epizootic VEEV strains emerge via mutation from enzootic progenitors that are incapable of efficient equine amplification, the molecular mechanism(s) involved remain enigmatic. The convergent evolution of E2 envelope glycoprotein mutations suggests that they are critical to VEEV emergence, but little is known about the role of non-envelope genes. We used the guinea pig, the small animal model that best predicts the ability to generate equine viremia, to assess the role of envelope versus other mutations in the epizootic phenotype. Using reciprocal chimeric viruses generated by swapping the envelope genes of closely related epizootic IC and enzootic ID strains, infections of guinea pigs demonstrated that envelope and non-envelope genes and sequences both contributed to virulence. However, early replication in lymphoid tissues appeared to be primarily envelope dependent.

Animals↗
PubMed2000

The evolution of song repertoires and immune defence in birds.

Song repertoires (the number of different song types sung by a male) in birds provide males with an advantage in sexual selection because females prefer males with large repertoires, and females may benefit because offspring sired by preferred males have high viability. Furthermore, males with large repertoires suffer less from malarial parasites, indicating that a large repertoire may reflect health status. We hypothesize that sexual selection may cause a coevolutionary increase in parasite virulence and host immune defence because sexual selection increases the risk of multiple infections that select for high virulence. Alternatively, a female mate preference for healthy males will affect the coevolutionary dynamics of host-parasite interactions by selecting for increased virulence and hence high investment by hosts in immune function. In a comparative study of birds, repertoire size and relative size of the spleen, which is an important immune defence organ, were strongly, positively correlated accounting for almost half of the variance. This finding suggests that host-parasite interactions have played an important role in the evolution of song repertoires in birds.

Animals↗
PubMed2005

Transcriptional profiling of Vibrio cholerae recovered directly from patient specimens during early and late stages of human infection.

Understanding gene expression by bacteria during the actual course of human infection may provide important insights into microbial pathogenesis. In this study, we evaluated the transcriptional profile of Vibrio cholerae, the causative agent of cholera, in clinical specimens from cholera patients. We collected samples of human stool and vomitus that were positive by dark-field microscopy for abundant vibrios and used a microarray to compare gene expression in organisms recovered directly from specimens collected during the early and late stages of human infection. Our results reveal that V. cholerae gene expression within the human host environment differs from patterns defined in in vitro models of pathogenesis. tcpA, the major subunit of the essential V. cholerae colonization factor, was significantly more highly expressed in early than in late stages of infection; however, the genes encoding cholera toxin were not highly expressed in either phase of human infection. Furthermore, expression of the virulence regulators toxRS and tcpPH was uncoupled. Interestingly, the pattern of gene expression indicates that the human upper intestine may be a uniquely suitable environment for the transfer of genetic elements that are important in the evolution of pathogenic strains of V. cholerae. These findings provide a more detailed assessment of the transcriptome of V. cholerae in the human host than previous studies of organisms in stool alone and have implications for cholera control and the design of improved vaccines.

Cholera↗
PubMed1998

Differential patterns of acquired virulence genes distinguish Salmonella strains.

Analysis of several Salmonella typhimurium in vivo-induced genes located in regions of atypical base composition has uncovered acquired genetic elements that cumulatively engender pathogenicity. Many of these regions are associated with mobile elements, encode predicted adhesin and invasin-like functions, and are required for full virulence. Some of these regions distinguish broad host range from host-adapted Salmonella serovars and may contribute to inherent differences in host specificity, tissue tropism, and disease manifestation. Maintenance of this archipelago of acquired sequence by selection in specific hosts reveals a fossil record of the evolution of pathogenic species.

Animals↗
PubMed2026

Salmonella uses sulfate reductases with unique catalytic activity to promote gut colonization in mice.

Non-typhoidal Salmonella use molybdenum cofactor-containing MopB- or DMSO reductase-family members to respire chemically diverse substrates, including formate, nitrate and methionine sulfoxide, during infection. The DmsABC enzymatic complex encodes one such DMSO reductase to promote oxidative stress resistance. The Salmonella genome encodes several gene paralogues but their role in virulence is unclear. Here we characterize three Salmonella MopB-family extracytoplasmic sulfate reductases, which we call Xsr1A, Xsr2A and Xsr3A. Infection experiments in mice and macrophages show that these sulfate reductases support Salmonella growth and virulence in the gut and during systemic infection, countering the oxidative effects of host respiratory burst activity. Further experiments show that they are molybdenum cofactor-independent enzymes, and instead depend on the nearby redox-active [4Fe-4S] prosthetic group for catalytic activity. Orthologues of these sulfate reductases were found across distant evolutionary branches, suggesting that [4Fe-4S]-dependent catalysis may occur across the ubiquitous MopB superfamily. Our findings offer insights into the modular evolution of redox centres in the widespread MopB superfamily.

Animals↗
PubMedDate not supplied

[Plasticity of bacterial genomes: pathogenicity islands and the locus of enterocyte effacement (LEE)].

Many bacterial virulence attributes, like toxins, adhesins, invasins, iron uptake systems, are encoded within specific regions of the bacterial genome. These in size varying regions are termed pathogenicity islands (PAIs) since they confer pathogenic properties to the respective micro-organism. Per definition PAIs are exclusively found in pathogenic strains and are often inserted near transfer-RNA genes. Nevertheless, non-pathogenic bacteria also possess foreign DNA elements that confer advantageous features, leading to improved fitness. These additional DNA elements as well as PAIs are termed genomic islands and were acquired during bacterial evolution. Significant G+C content deviation in pathogenicity islands with respect to the rest of the genome, the presence of direct repeat sequences at the flanking regions, the presence of integrase gene determinants as other mobility features,the particular insertion site (tRNA gene) as well as the observed genetic instability suggests that pathogenicity islands were acquired by horizontal gene transfer. PAIs are the fascinating proof of the plasticity of bacterial genomes. PAIs were originally described in human pathogenic Escherichia (E.) coli strains. In the meantime PAIs have been found in various pathogenic bacteria of humans, animals and even plants. The Locus of Enterocyte Effacement (LEE) is one particular widely distributed PAI of E coli. In addition, it also confers pathogenicity to the related species Citrobacter (C.) rodentium and Escherichia (E.) alvei. The LEE is an important virulence feature of several animal pathogens. It is an obligate PAI of all animal and human enteropathogenic E. coli (EPEC), and most enterohaemorrhegic E. coli (EHEC) also harbor the LEE. The LEE encodes a type III secretion system, an adhesion (intimin) that mediates the intimate contact between the bacterium and the epithelial cell, as well as various proteins which are secreted via the type III secretion system. The LEE encoded virulence features are responsible for the formation of so called attaching and effacing (AE) lesions in the intestinal epithelium. Due to its wide distribution in animal pathogens, LEE encoded antigens are suitable vaccine antigens. Acquisition and structure of the LEE pathogenicity island is the crucial point of numerous investigations. However, the evolution of the LEE, its origin and further spread in E. coli, are far from being resolved.

Bacteria↗
PubMed2005

Enterohaemorrhagic E. coli in veterinary medicine.

The emergence of enterohaemorrhagic Escherichia coli (EHEC) as major human pathogens began with the identification of serotype O157:H7 in the early 1980s as the cause of various food-borne outbreaks of severe intestinal disease. The key virulence factors include verocytotoxins (Vt) and effectors and adhesins associated with type III secretion systems. Tracing the origins of human outbreaks reveals that the primary source of this organism is the ruminant gastro-intestinal tract and a variety of transmission routes to humans have been identified. The epidemiology of E. coli O157:H7 within cattle and other ruminants has been studied extensively and the prevalence of non-O157:H7 serotypes contrasts with the observed dominance of E. coli O157:H7 amongst human EHEC isolates. Although there is some evidence that EHEC cause disease in young animals, the high prevalence of Vt within healthy ruminants suggests that this is not a virulence factor within these species. An understanding of the mechanisms underpinning EHEC persistence within their natural reservoir hosts and the development of a molecular understanding of EHEC biology and evolution could eventually allow a reduction in the incidence of human disease and may reduce future threats. The use of animal models to replicate and study human EHEC pathogenesis is described.

Animals↗
PubMed2005

Design, validation, and application of a seven-strain Staphylococcus aureus PCR product microarray for comparative genomics.

Bacterial comparative genomics has been revolutionized by microarrays, but the power of any microarray is dependent on the number and diversity of gene reporters it contains. Staphylococcus aureus is an important human pathogen causing a wide range of invasive and toxin-mediated diseases, and more than 20% of the genome of any isolate consists of variable genes. Seven whole-genome sequences of S. aureus are available, and we exploited this rare opportunity to design, build, and validate a comprehensive, nonredundant PCR product microarray carrying reporters that represent every predicted open reading frame (3,623 probes). Such a comprehensive microarray necessitated a novel design strategy. Validation with the seven sequenced strains showed correct identification of 93.9% of genes present or absent/divergent but was dependent on the method of analysis chosen. Microarray data were highly reproducible, reducing the need for many replicate slides. Interpretation of microarray data was enhanced by focusing on the major areas of variation--the presence or absence of mobile genetic elements (MGEs). We compiled "composite genomes" of every individual MGE and visualized their distribution. This allowed the sensitive discrimination of related isolates, including the first clear description of how isolates of the same clone of epidemic methicillin-resistant S. aureus differ substantially in their carriage of MGEs. These MGEs carry virulence and resistance genes, suggesting differences in pathogenic potential. The novel methods of design and interpretation of data generated from this microarray will enable further studies of S. aureus evolution, epidemiology, and pathogenesis.

Bacterial Proteins↗
PubMed2006

Deterministic, compensatory mutational events in the capsid of foot-and-mouth disease virus in response to the introduction of mutations found in viruses from persistent infections.

The evolution of foot-and-mouth disease virus (FMDV) (biological clone C-S8c1) in persistently infected cells led to the emergence of a variant (R100) that displayed increased virulence, reduced stability, and other modified phenotypic traits. Some mutations fixed in the R100 genome involved a cluster of highly conserved residues around the capsid pores that participate in interactions with each other and/or between capsid protomers. We have investigated phenotypic and genotypic changes that occurred when these replacements were introduced into the C-S8c1 capsid. The C3007V and M3014L mutations exerted no effect on plaque size or viral yield during lytic infections, or on virion stability, but led to a reduction in biological fitness; the D3009A mutation caused drastic reductions in plaque size and viability. Remarkably, competition of the C3007V mutant with the nonmutated virus invariably resulted in the fixation of the D3009A mutation in the C3007V capsid. In turn, the presence of the D3009A mutation invariably led to the fixation of the M3014L mutation. In both cases, two individually disadvantageous mutations led, together, to an increase in fitness, as the double mutants outcompeted the nonmutated genotype. The higher fitness of C3007V/D3009A was related to a faster multiplication rate. These observations provide evidence for a chain of linked, compensatory mutational events in a defined region of the FMDV capsid. Furthermore, they indicate that the clustering of unique amino acid replacements in viruses from persistent infections may also occur in cytolytic infections in response to changes caused by previous mutations without an involvement of the new mutations in the adaptation to a different environment.

Adaptation, Physiological↗
PubMed1992

Protection of mice and swine from pseudorabies virus conferred by vaccinia virus-based recombinants.

Glycoproteins gp50, gII, and gIII of pseudorabies virus (PRV) were expressed either individually or in combination by vaccinia virus recombinants. In vitro analysis by immunoprecipitation and immunofluorescence demonstrated the expression of a gII protein of approximately 120 kDa that was proteolytically processed to the gIIb (67- to 74-kDa) and gIIc (58-kDa) mature protein species similar to those observed in PRV-infected cells. Additionally, the proper expression of the 90-kDa gIII and 50-kDa gp50 was observed. All three of these PRV-derived glycoproteins were detectable on the surface of vaccinia virus-PRV recombinant-infected cells. In vivo, mice were protected against a virulent PRV challenge after immunization with the PRV glycoprotein-expressing vaccinia virus recombinants. The coexpression of gII and gIII by a single vaccinia virus recombinant resulted in a significantly reduced vaccination dose required to protect mice against PRV challenge. Inoculation of piglets with the various vaccinia virus-PRV glycoprotein recombinants also resulted in protection against virulent PRV challenge as measured by weight gain. The simultaneous expression of gII and gp50 in swine resulted in a significantly enhanced level of protection as evaluated by weight evolution following challenge with live PRV.

Animals↗
PubMed2004

An approach to large scale identification of non-obvious structural similarities between proteins.

BACKGROUND: A new sequence independent bioinformatics approach allowing genome-wide search for proteins with similar three dimensional structures has been developed. By utilizing the numerical output of the sequence threading it establishes putative non-obvious structural similarities between proteins. When applied to the testing set of proteins with known three dimensional structures the developed approach was able to recognize structurally similar proteins with high accuracy. RESULTS: The method has been developed to identify pathogenic proteins with low sequence identity and high structural similarity to host analogues. Such protein structure relationships would be hypothesized to arise through convergent evolution or through ancient horizontal gene transfer events, now undetectable using current sequence alignment techniques. The pathogen proteins, which could mimic or interfere with host activities, would represent candidate virulence factors. The developed approach utilizes the numerical outputs from the sequence-structure threading. It identifies the potential structural similarity between a pair of proteins by correlating the threading scores of the corresponding two primary sequences against the library of the standard folds. This approach allowed up to 64% sensitivity and 99.9% specificity in distinguishing protein pairs with high structural similarity. CONCLUSION: Preliminary results obtained by comparison of the genomes of Homo sapiens and several strains of Chlamydia trachomatis have demonstrated the potential usefulness of the method in the identification of bacterial proteins with known or potential roles in virulence.

Bacterial Proteins↗
PubMedDate not supplied

Invasive amebiasis in a spider monkey (Ateles geoffroyi). Case report and a short review of the literature of amebiasis in non-human primates.

A spider monkey (Ateles geoffroyi) studied at the San Juan de Aragon Zoo died with symptoms of amoebic dysentery verified by coprologic investigation of the parasite, his female partner was cured with conventional antiamoebic treatment. At autopsy widespread ulcerations in the colon and multiple liver abscesses were found, containing trophozoites of Entamoeba histolytica. Both lesions were identical to those observed in human amoebiasis. A short review of the literature in nonhuman primates infections points out that the so-called spontaneous amoebiasis seen in colonies of captive monkeys, and transmission to their newborns within the same species of monkeys, have been in contact with humans. It is proposed that amoebiasis in monkeys should be considered as an excellent model for experimental studies on amoebiasis because other phylogenetically distant species have shown different pathology or are resistant to the infection. Also, it should raise concern that monkeys may become carriers of cysts and trophozoites of virulent strains of E. histolytica. Entamoeba histolytica DNA hybridization techniques should be considered for comparing genomic similarities with other protozoa, including the genera Amoeba to establish its pattern of evolution.

Animals↗
PubMed1991

[Deep venous thrombosis of the upper extremity].

After a description of this disease, the authors report on a clinical case they observed, and the evolution of this case over a period of time. In analysing this case and comparing the data reported in the literature, we want to underline the high degree of virulence in this disease over a period of time, due to the frequency of the development of chronic cases. We would like to point out that surgeons should rely on surgical procedures and a new decompression technique rather than relying on pharmacological therapy, as the best way of definitively resolving a chronic stasis. This is particularly important in acute manifestations of the disease where the limb is in serious danger.

Acute Disease↗
PubMed1990

[Evolution of recombination in "host-parasite" systems. Multilocus models].

Evolution of the recombination system caused by antagonistic species interactions (host and parasite, for example) was studied. The genetic structure of host population as well as that of parasite is explicitly present in our models. The selection intensity depends on host's resistance and parasite's virulence, both controlled by polygenic systems. The rec-system dynamics was numerically studied using the genetic operators method. It is shown that high-recombination alleles of the rec-modificator can have a short-term selective advantage in both interacting populations simultaneously.

Animals↗
PubMed1998

Evolution of a simian immunodeficiency virus pathogen.

Analysis of disease induction by simian immunodeficiency viruses (SIV) in macaques was initially hampered by a lack of molecularly defined pathogenic strains. The first molecularly cloned SIV strains inoculated into macaques, SIVmacBK28 and SIVmacBK44 (hereafter designated BK28 and BK44, respectively), were cases in point, since they failed to induce disease within 1 year postinoculation in any inoculated animal. Here we report the natural history of infection with BK28 and BK44 in inoculated rhesus macaques and efforts to increase the pathogenicity of BK28 through genetic manipulation and in vivo passage. BK44 infection resulted in no disease in four animals infected for more than 7 years, whereas BK28 induced disease in less than half of animals monitored for up to 7 years. Elongation of the BK28 transmembrane protein (TM) coding sequence truncated by prior passage in human cells marginally increased pathogenicity, with two of four animals dying in the third year and one dying in the seventh year of infection. Modification of the BK28 long terminal repeat to include four consensus nuclear factor SP1 and two consensus NF-kappaB binding sites enhanced early virus replication without augmenting pathogenicity. In contrast, in vivo passage of BK28 from the first animal to die from immunodeficiency disease (1.5 years after infection) resulted in a consistently pathogenic strain and a 50% survival time of about 1.3 years, thus corresponding to one of the most pathogenic SIV strains identified to date. To determine whether the diverse viral quasispecies that evolved during in vivo passage was required for pathogenicity or whether a more virulent virus variant had evolved, we generated a molecular clone composed of the 3' half of the viral genome derived from the in vivo-passaged virus (H824) fused with the 5' half of the BK28 genome. Kinetics of disease induction with this cloned virus (BK28/H824) were similar to those with the in vivo-passaged virus, with four of five animals surviving less than 1.7 years. Thus, evolution of variants with enhanced pathogenicity can account for the increased pathogenicity of this SIV strain. The genetic changes responsible for this virulent transformation included at most 59 point mutations and 3 length-change mutations. The critical mutations were likely to have been multiple and dispersed, including elongation of the TM and Nef coding sequences; changes in RNA splice donor and acceptor sites, TATA box sites, and Sp1 sites; multiple changes in the V2 region of SU, including a consensus neutralization epitope; and five new N-linked glycosylation sites in SU.

Amino Acid Sequence↗