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PubMed2001

Pathogenicity, morphology, and differentiation of Acanthamoeba.

Acanthamoeba keratitis is sight threatening corneal infection caused by pathogenic Acanthamoeba. Previous studies have shown the genotypic differences between pathogenic and non-pathogenic species/strains of Acanthamoeba. In this study, we examined the morphological differences between pathogenic and non-pathogenic species/strains using scanning electron microscopy. Pathogenic Acanthamoeba exhibited higher number of acanthopodia (structures associated with the binding of amoeba to the target cells) as compared to non-pathogens. In addition, interactions of amoeba with the corneal epithelial cells were studied. Only pathogenic amoeba exhibited adhesion to epithelial cells. Further results indicated that phagocytosis occurs in the pathogenic amoeba by the formation of amoebastome (characteristic of amoeba phagocyte). This study showed that Acanthamoeba phagocytosis may be both an efficient means of obtaining nutrients for the amoeba and a significant factor in the pathogenesis of Acanthamoeba infections.

Acanthamoeba↗

PubMed2006

Helminths as vectors of pathogens in vertebrate hosts: a theoretical approach.

Pathogens frequently use vectors to facilitate transmission between hosts and, for vertebrate hosts, the vectors are typically ectoparasitic arthropods. However, other parasites that are intimately associated with their hosts may also be ideal candidate vectors; namely the parasitic helminths. Here, we present empirical evidence that helminth vectoring of pathogens occurs in a range of vertebrate systems by a variety of helminth taxa. Using a novel theoretical framework we explore the dynamics of helminth vectoring and determine which host-helminth-pathogen characteristics may favour the evolution of helminth vectoring. We use two theoretical models: the first is a population dynamic model amalgamated from standard macro- and microparasite models, which serves as a framework for investigation of within-host interactions between co-infecting pathogens and helminths. The second is an evolutionary model, which we use to predict the ecological conditions under which we would expect helminth vectoring to evolve. We show that, like arthropod vectors, helminth vectors increase pathogen fitness. However, unlike arthropod vectors, helminth vectoring increases the pathogenic impact on the host and may allow the evolution of high pathogen virulence. We show that concomitant infection of a host with a helminth and pathogen are not necessarily independent of one another, due to helminth vectoring of microparasites, with profound consequences for pathogen persistence and the impact of disease on the host population.

Animals↗

PubMed2006

Mitochondrial tRNA sequences as unusual replication origins: pathogenic implications for Homo sapiens.

The heavy strand of vertebrate mitochondrial genomes accumulates deaminations proportionally to the time it spends single-stranded during replication. A previous study showed that the strength of genome-wide deamination gradients originating from tRNA gene's locations increases with their capacities to form secondary structures resembling mitochondrial origins of light strand replication (OL), suggesting an alternative function for tRNA sequences. We hypothesize that this function is frequently pathogenic for those tRNA genes that normally do not form OL-like structures, because this could cause excess mutations in genome regions unadapted to tolerate them. In human mitochondrial genomes, pathogenic tRNA variants usually form less OL-like structures than non-pathogenic ones in cases where the normal non-pathogenic tRNA variant can function as OL, as evolutionary analyses reveal. For tRNAs lacking the putative OL-like functioning capacity, pathogenic variants form more OL-like secondary structures, particularly structures that might invoke bi-directional replication (true for 14 among 21 tRNA species, p<0.05, sign test; significantly at p<0.05 (1 tailed test) for 7 tRNA species), but not more unidirectional replication invoking structures. Accounting for the functional cloverleaf-like structure-forming capacities of tRNAs yields similar results. Rare, non-pathogenic tRNA mutants tend to form more OL-like structures than the common, non-pathogenic ones, suggesting weak directional selection also among non-pathogenic variants. The duration spent single stranded by a region of the heavy strand (D(ssH)) during replication, estimated by integrating over all regions that can function as OL in Homo sapiens mitochondrial genomes, increases with distance of that region from the Dloop. This suggests convergence of single-strandedness during replication and transcription, and explains conserved locations of tRNA species in mitochondrial genomes and bacterial operons. These locations minimize deamination costs only in anticodons and not in other tRNA regions, during replication and transcription. Therefore, putative functioning as OLs by tRNA sequences is normal at some locations and pathogenic at others.

Aging↗

PubMed2006

Pathogenic potential of North American H7N2 avian influenza virus: a mutagenesis study using reverse genetics.

An H7N2 subtype avian influenza virus (AIV) first appeared in the live bird marketing system (LBMS) in the Northeastern United States in 1994. Since then this lineage of virus has become the predominant subtype of AIV isolated from the LBMS and has been linked to several costly commercial poultry outbreaks. Concern for this low pathogenicity isolate mutating to the highly pathogenic form has remained high because of the increasing number of basic amino acids at the hemagglutinin (HA) cleavage site, which is known to be associated with increased pathogenicity of AIV. To address the risk of low pathogenic LBMS-lineage H7N2 virus mutating to the highly pathogenic form of the virus, we generated a series of mutant viruses that have changes in the sequence at the HA cleavage site by using plasmid-based reverse genetics. We confirmed that a conserved proline at -5 position from the HA cleavage site could be changed to a basic amino acid, producing a virus with five basic amino acids in a row at the cleavage site, but with no increase in virulence. Increased virulence was only observed when additional basic amino acids were inserted. We also observed that the virus preferred the arginine instead of lysine at the -4 position from the cleavage site to manifest increased virulence both in vitro and in vivo. Using helper virus-based reverse genetics, where only one transcription plasmid expressing a mutated HA vRNA is used, we identified specific HA cleavage site sequences that were preferentially incorporated into the low pathogenic wild-type virus. The resultant reassortant viruses were highly pathogenic in chickens. This study provides additional evidence that H7 avian influenza viruses require an insertional event to become highly pathogenic, as compared to H5 viruses that can become highly pathogenic strictly by mutation or by insertions.

Amino Acid Sequence↗

PubMed1991

A host-host-pathogen model with free-living infective stages, applicable to microbial pest control.

A model has been investigated of the dynamics of the interaction between two hosts which are both attacked by a common pathogen, where the pathogen has free-living infective stages the population size of which must itself be modelled explicitly, and where the host species do not interact with one another except through their shared pathogen. If either host interacted with the pathogen alone, three broad classes of dynamics would be possible: host regulation, pathogen persistence and pathogen extinction. Here, all possible types of combinations of hosts are examined: regulation-regulation (both hosts would be regulated if they interacted with the pathogen alone), regulation-persistence, regulation-extinction, persistence-persistence persistence-extinction and extinction-extinction. A wide range of dynamics is generated, including a number of patterns quite unlike those found in the one-host pathogen case (e.g. persistence in one host, elimination of the other host) and behaviour contingent on initial densities in the system. For clarity and pertinence, attention is focused on the case where one host is a pest, the pathogen is a potential microbial control agent, and the other host is a non-target species which it is undesirable to harm. The model suggests, broadly, that non-targets are unlikely to be seriously threatened in such cases, and also that non-targets, far from undermining pest control, are quite likely to contribute to its efficacy.

Animals↗

PubMed2000

Assessing the consequences of global change for forest disturbance from herbivores and pathogens.

Herbivores and pathogens impact the species composition, ecosystem function, and socioeconomic value of forests. Herbivores and pathogens are an integral part of forests, but sometimes produce undesirable effects and a degradation of forest resources. In the United States, a few species of forest pests routinely have significant impacts on up to 20 million ha of forest with economic costs that probably exceed $1 billion/year. Climatic change could alter patterns of disturbance from herbivores and pathogens through: (1) direct effects on the development and survival of herbivores and pathogens; (2) physiological changes in tree defenses; and (3) indirect effects from changes in the abundance of natural enemies (e.g. parasitoids of insect herbivores), mutualists (e.g. insect vectors of tree pathogens), and competitors. Because of their short life cycles, mobility, reproductive potential, and physiological sensitivity to temperature, even modest climate change will have rapid impacts on the distribution and abundance of many forest insects and pathogens. We identify 32 syndromes of biotic disturbance in North American forests that should be carefully evaluated for their responses to climate change: 15 insect herbivores, browsing mammals; 12 pathogens; 1 plant parasite; and 3 undiagnosed patterns of forest decline. It is probable that climatic effects on some herbivores and pathogens will impact on biodiversity, recreation, property value, forest industry, and even water quality. Some scenarios are beneficial (e.g. decreased snow cover may increase winter mortality of some insect pests), but many are detrimental (e.g. warming tends to accelerate insect development rate and facilitate range expansions of pests and climate change tends to produce a mismatch between mature trees and their environment, which can increase vulnerability to herbivores and pathogens). Changes in forest disturbance can produce feedback to climate through affects on water and carbon flux in forest ecosystems; one alarming scenario is that climate warming may increase insect outbreaks in boreal forests, which would tend to increase forest fires and exacerbate further climate warming by releasing carbon stores from boreal ecosystems. We suggest a list of research priorities that will allow us to refine these risk assessments and adopt forest management strategies that anticipate changes in biotic disturbance regimes and mitigate the ecological, social, and economic risks.

Animal Nutritional Physiological Phenomena↗

PubMed2006

Antigen presentation and the ubiquitin-proteasome system in host-pathogen interactions.

Relatively small genomes and high replication rates allow viruses and bacteria to accumulate mutations. This continuously presents the host immune system with new challenges. On the other side of the trenches, an increasingly well-adjusted host immune response, shaped by coevolutionary history, makes a pathogen's life a rather complicated endeavor. It is, therefore, no surprise that pathogens either escape detection or modulate the host immune response, often by redirecting normal cellular pathways to their advantage. For the purpose of this chapter, we focus mainly on the manipulation of the class I and class II major histocompatibility complex (MHC) antigen presentation pathways and the ubiquitin (Ub)-proteasome system by both viral and bacterial pathogens. First, we describe the general features of antigen presentation pathways and the Ub-proteasome system and then address how they are manipulated by pathogens. We discuss the many human cytomegalovirus (HCMV)-encoded immunomodulatory genes that interfere with antigen presentation (immunoevasins) and focus on the HCMV immunoevasins US2 and US11, which induce the degradation of class I MHC heavy chains by the proteasome by catalyzing their export from the endoplasmic reticulum (ER)-membrane into the cytosol, a process termed ER dislocation. US2- and US11-mediated subversion of ER dislocation ensures proteasomal degradation of class I MHC molecules and presumably allows HCMV to avoid recognition by cytotoxic T cells, whilst providing insight into general aspects of ER-associated degradation (ERAD) which is used by eukaryotic cells to purge their ER of defective proteins. We discuss the similarities and differences between the distinct pathways co-opted by US2 and US11 for dislocation and degradation of human class I MHC molecules and also a putatively distinct pathway utilized by the murine herpes virus (MHV)-68 mK3 immunoevasin for ER dislocation of murine class I MHC. We speculate on the implications of the three pathogen-exploited dislocation pathways to cellular ER quality control. Moreover, we discuss the ubiquitin (Ub)-proteasome system and its position at the core of antigen presentation as proteolysis and intracellular trafficking rely heavily on Ub-dependent processes. We add a few examples of manipulation of the Ub-proteasome system by pathogens in the context of the immune system and such diverse aspects of the host-pathogen relationship as virus budding, bacterial chromosome integration, and programmed cell death, to name a few. Finally, we speculate on newly found pathogen-encoded deubiquitinating enzymes (DUBs) and their putative roles in modulation of host-pathogen interactions.

Animals↗

PubMed2005

Enhanced pro-inflammatory chemokine/cytokine response triggered by pathogenic Entamoeba histolytica : basis of invasive disease.

The virulence of Entamoeba histolytica is governed by adhesion/colonization in the gut which is mediated by a galactose specific lectin. Two morphologically identical but distinct species i.e. pathogenic E. histolytica and non-pathogenic E. dispar, can be differentiated by distinct epitopes in the lectin. Both species bind to colonic epithelial cells, but only E. histolytica infection induces an inflammatory response and subsequent pathogenesis. Thus, comparing the responses of the intestinal cells to pathogenic and non-pathogenic lectins is a point of interest. The pathogenic lectin causes cytolysis of epithelial and immune-competent cells. Our data (both qualitative and mRNA quantitation) indicate that the epithelial cells responded to E. histolytica lectin with an increased expression of pro-inflammatory IL-2, IL-6, IL-8, MIP-1alpha, MCP-1, RANTES, GROalpha and GMCSF as compared to E. dispar lectin. The pathogenic LCM induced a significant increase in intracellular calcium concentration, proliferative response and chemotaxis of lymphocytes from ALA patients as compared to non-pathogenic LCM. High RANTES and IL-6 were induced in patients' lymphocytes by pathogenic LCM, along with their receptors CCR5 and CD126 as compared to NP-LCM. The local release of such a complex network of cytokines/chemokines could explain the histopathology of E. histolytica infection. The comparative low levels of these chemokines/pro-inflammatory cytokines and high levels of anti-inflammatory IL-10 in response to non-pathogenic E. dispar could explain the absence of an acute inflammatory response and the disease process. The cytokines and chemokines may provide a mechanism for initiation, amplification or containment of inflammation during disease state.

Agglutination Tests↗

PubMed2006

The origin of human pathogens: evaluating the role of agriculture and domestic animals in the evolution of human disease.

Many significant diseases of human civilization are thought to have arisen concurrently with the advent of agriculture in human society. It has been hypothesised that the food produced by farming increased population sizes to allow the maintenance of virulent pathogens, i.e. civilization pathogens, while domestic animals provided sources of disease to humans. To determine the relationship between pathogens in humans and domestic animals, I examined phylogenetic data for several human pathogens that are commonly evolutionarily linked to domestic animals: measles, pertussis, smallpox, tuberculosis, taenid worms, and falciparal malaria. The majority are civilization pathogens, although I have included others whose evolutionary origins have traditionally been ascribed to domestic animals. The strongest evidence for a domestic-animal origin exists for measles and pertussis, although the data do not exclude a non-domestic origin. As for the other pathogens, the evidence currently available makes it difficult to determine if the domestic-origin hypothesis is supported or refuted; in fact, intriguing data for tuberculosis and taenid worms suggests that transmission may occur as easily from humans to domestic animals. These findings do not abrogate the importance of agriculture in disease transmission; rather, if anything, they suggest an alternative, more complex series of effects than previously elucidated. Rather than domestication, the broader force for human pathogen evolution could be ecological change, namely anthropogenic modification of the environment. This is supported by evidence that many current emerging infectious diseases are associated with human modification of the environment. Agriculture may have changed the transmission ecology of pre-existing human pathogens, increased the success of pre-existing pathogen vectors, resulted in novel interactions between humans and wildlife, and, through the domestication of animals, provided a stable conduit for human infection by wildlife diseases.

Agriculture↗

PubMed1999

A bacteriophage encoding a pathogenicity island, a type-IV pilus and a phage receptor in cholera bacteria.

The virulence properties of many pathogenic bacteria are due to proteins encoded by large gene clusters called pathogenicity islands, which are found in a variety of human pathogens including Escherichia coli, Salmonella, Shigella, Yersinia, Helicobacter pylori, Vibrio cholerae, and animal and plant pathogens such as Dichelobacter nodosus and Pseudomonas syringae. Although the presence of pathogenicity islands is a prerequisite for many bacterial diseases, little is known about their origins or mechanism of transfer into the bacterium. The bacterial agent of epidemic cholera, Vibrio cholerae, contains a bacteriophage known as cholera-toxin phage (CTXphi), which encodes the cholera toxin, and a large pathogenicity island called the VPI (for V. cholerae pathogenicity island) which itself encodes a toxin-coregulated pilus that functions as a colonization factor and as a CTXphi receptor. We have now identified the VPI pathogenicity island as the genome of another filamentous bacteriophage, VPIphi. We show that VPIphi is transferred between V. cholerae strains and provide evidence that the TcpA subunit of the toxin-coregulated type IV pilus is in fact a coat protein of VPIphi. Our results are the first description of a phage that encodes a receptor for another phage and of a virus-virus interaction that is necessary for bacterial pathogenicity.

Bacterial Outer Membrane Proteins↗

PubMed1989

The potential role of pathogens in biological control.

It is now well established that pathogens such as viruses, fungi bacteria and protozoans can have profound effects on the dynamics of their invertebrate host populations. Theoretical models of invertebrate host-pathogen interactions which assume uniform structure of the pathogen population may reasonably explain the oscillatory behaviour observed in some systems, but do not adequately describe the existence of more constant populations found in other host-pathogen interactions. An examination of the literature relating to these relatively stable systems suggests that the common thread is the eventual transmission of some of the more protected, longer-lived stages of the pathogen occurring in reservoirs, such as the soil, host cadavers on trees, or the live host itself. In this letter, I propose a new theoretical model which incorporates this population structure and accounts for the range of dynamics observed in natural systems. In particular, I show that host populations may be regulated to low and relatively constant densities if sufficient numbers of pathogens are trans-located from pathogen reservoirs to habitats where transmission can occur. An understanding of pathogen reservoirs may be of value in the design of biological control programmes and may greatly increase the effectiveness of pathogens as biological control agents.

Animals↗

PubMed1996

Moraxella catarrhalis: pathogenic significance in respiratory tract infections treated by community practitioners.

We prospectively studied the pathogenic significance of Moraxella (Branhamella) catarrhalis isolated from 212 patients of community practitioners in Australia. This organism was most commonly isolated during winter and early spring, and 92% of isolates were beta-lactamase producers. On the basis of predetermined clinical and microbiological criteria, 42% of the isolates were definitely pathogenic, 7% were probably pathogenic, 21% were of indeterminate pathogenicity, and 30% were nonpathogenic. Factors associated with pathogenic significance included pneumonia or bronchitis (87% of patients), predisposing respiratory or systemic conditions (62%), isolation from sputum, and pure isolation. Thirty-six percent of patients were < 5 years old, but only 9% of isolates from these patients were pathogenic or probably pathogenic, a finding that reflects the fact that nasal-swab and nasopharyngeal-aspirate sampling is a common practice. Isolates from older patients were more likely to be pathogenically significant. An assessment of the pathogenic significance of M. catarrhalis isolated from a patient in a community practice should take into consideration factors such as the patient's age, clinical illness, and underlying conditions; the presence of other organisms; and the source of the isolate.

Adolescent↗

PubMed2003

Recurrent acute otitis media occurring within one month from completion of antibiotic therapy: relationship to the original pathogen.

OBJECTIVES: (1) To determine the relationship between acute otitis media (AOM) pathogens isolated in cases of early clinical recurrence of AOM (occurring within 1 month from completion of therapy) to the original pathogens causing the initial AOM episode; and (2) To determine whether shorter time intervals between completion of antibiotic therapy and clinical recurrences of AOM are associated with higher rates of true bacteriologic relapse. PATIENTS AND METHODS: From 1995 through 2000, 1077 infants and young children ages 3 to 36 months with AOM were enrolled in double tympanocentesis (performed on Day 1 in all patients and Days 4 to 6 in those initially culture-positive) studies. Of these, 834 (77%) completed successfully the antibiotic treatment [pathogen eradication on Days 4 to 6 of therapy or no pathogen on middle ear fluid (MEF) culture on Day 1 and clinical improvement at end of therapy]. Patients were followed for 3 to 4 weeks after completion of therapy, and additional MEF cultures were obtained if clinical recurrence occurred. True bacteriologic relapse was defined as the presence of a pathogen identical with that isolated before therapy by serotype and pulsed field gel electrophoresis for and by pulsed field gel electrophoresis for Streptococcus pneumoniae and beta-lactamase production for Haemophilus influenzae. RESULTS: MEF cultures were performed in 108 consecutive patients with early recurrent AOM. One hundred pathogens were isolated at recurrence in 88 of 108 (81%) patients: 54 H. influenzae; 45 S. pneumoniae; and 1 Moraxella catarrhalis. Most recurrent AOM episodes developed during the first 2 weeks of follow-up; 39 (36%), 38 (35%), 21 (19%) and 10 (9%) recurrent AOM episodes occurred on Days 1 to 7, 8 to 14, 15 to 21 and 22 to 28 after completion of therapy, respectively. In most patients these episodes were caused by a new pathogen. True bacteriologic relapses were found in 30 (28%) of 108 patients whose MEF cultures were positive for 35 pathogens: 13 of 108 (12%) S. pneumoniae; 12 of 108 (11%) H. influenzae; and 5 of 108 (5%) both. When timing of recurrent AOM after completion of therapy was analyzed, true bacteriologic relapses were found in 16 of 39 (41%), 10 of 38 (26%), 3 of 21 (14%) and 1 of 10 (10%) of all episodes on Days 1 to 7, 8 to 14, 15 to 21 and 22 to 28 after completion of therapy, respectively (P = 0.01). The respective rates for were 11 of 17 (65%), 3 of 10 (30%), 3 of 13 (23%) and 1 of 5 (20%) (P = 0.02). For H. influenzae the respective rates were 8 of 19 (42%), 9 of 23 (39%), 0 of 8 (0%) and 0 of 4 (0%) (P = 0.02). CONCLUSIONS: Most recurrent AOM episodes occurring within 1 month from completion of antibiotic therapy are in fact new infections. Most of the true bacteriologic AOM relapses occur within 14 days after completion of therapy, but even during this time interval most of the recurrences are caused by new pathogens. H. influenzae is very unlikely to cause true bacteriologic AOM relapses 14 days or later after completion of therapy.

Acute Disease↗

PubMed2004

Competition for attachment of aquaculture candidate probiotic and pathogenic bacteria on fish intestinal mucus.

Probiotics for aquaculture are generally only selected by their ability to produce antimicrobial metabolites; however, attachment to intestinal mucus is important in order to remain within the gut of its host. Five candidate probiotics (AP1-AP5), isolated from the clownfish, Amphiprion percula (Lacepéde), were examined for their ability to attach to fish intestinal mucus and compete with two pathogens, Aeromonas hydrophila and Vibrio alginolyticus. Two different radioactive isotopes were used to quantify competition between pathogens and probionts. Attachment of the pathogens was enhanced by the presence of the candidate probiotics. However, the addition of the candidate probiotics after the pathogens resulted in reduced pathogen attachment. Only AP5 caused lower attachment success of V. alginolyticus when added before the pathogen. When AP5 was added first, the average attachment change was 41% compared with 72% when added after V. alginolyticus, suggesting that the probiotic is displaced but that enhanced attachment of the pathogen does not occur. Conversely, when V. alginolyticus was added first, followed by AP5, attachment change was 37% while AP5 had 92% attachment change when added second. This implies that the pathogen was displaced by the candidate probiotic and therefore it appeared that, based on the ability of probiont AP5 to attach to mucus, the growth of the pathogen in the digestive tract might be suppressed by the candidate probiont's presence.

Aeromonas hydrophila↗

PubMed2007

System for simultaneous detection of 16 pathogens related to urethritis to diagnose mixed infection.

OBJECTIVE: Urethritis is not always caused by a single pathogen, and isolation of more than two pathogens from one patient is not uncommon. We developed a method to simultaneously detect 16 pathogens related to urethritis. METHODS: We designed specific primers used for amplification of urethritis pathogens in our 16-well microplate assay. Sixteen microliters of each reaction mixture containing template DNA was added to each well to amplify 16 pathogens simultaneously. RESULTS: After we evaluated the specificity and sensitivity of this microplate polymerase chain reaction method, we used it to detect pathogens in clinical samples. Of 163 clinical samples, 49.7% (81/163) were positive for specific pathogens, and 6.7% (11/163) showed mixed infection. A specific pathogen was not identified in 43.6% (71/163) of cases. CONCLUSIONS: We developed a 16-well microplate assay with 16 specific primers to identify pathogens associated with urethritis.

Humans↗

PubMed2006

Application of comparative phylogenomics to study the evolution of Yersinia enterocolitica and to identify genetic differences relating to pathogenicity.

Yersinia enterocolitica, an important cause of human gastroenteritis generally caused by the consumption of livestock, has traditionally been categorized into three groups with respect to pathogenicity, i.e., nonpathogenic (biotype 1A), low pathogenicity (biotypes 2 to 5), and highly pathogenic (biotype 1B). However, genetic differences that explain variation in pathogenesis and whether different biotypes are associated with specific nonhuman hosts are largely unknown. In this study, we applied comparative phylogenomics (whole-genome comparisons of microbes with DNA microarrays combined with Bayesian phylogenies) to investigate a diverse collection of 94 strains of Y. enterocolitica consisting of 35 human, 35 pig, 15 sheep, and 9 cattle isolates from nonpathogenic, low-pathogenicity, and highly pathogenic biotypes. Analysis confirmed three distinct statistically supported clusters composed of a nonpathogenic clade, a low-pathogenicity clade, and a highly pathogenic clade. Genetic differences revealed 125 predicted coding sequences (CDSs) present in all highly pathogenic strains but absent from the other clades. These included several previously uncharacterized CDSs that may encode novel virulence determinants including a hemolysin, a metalloprotease, and a type III secretion effector protein. Additionally, 27 CDSs were identified which were present in all 47 low-pathogenicity strains and Y. enterocolitica 8081 but absent from all nonpathogenic 1A isolates. Analysis of the core gene set for Y. enterocolitica revealed that 20.8% of the genes were shared by all of the strains, confirming this species as highly heterogeneous, adding to the case for the existence of three subspecies of Y. enterocolitica. Further analysis revealed that Y. enterocolitica does not cluster according to source (host).

Animals↗

PubMed1996

The relationship between capsid protein (VP2) sequence and pathogenicity of Aleutian mink disease parvovirus (ADV): a possible role for raccoons in the transmission of ADV infections.

Aleutian mink disease parvovirus (ADV) DNA was identified by PCR in samples from mink and raccoons on commercial ranches during an outbreak of Aleutian disease (AD). Comparison of DNA sequences of the hypervariable portion of VP2, the major capsid protein of ADV, indicated that both mink and raccoons were infected by a new isolate of ADV, designated ADV-TR. Because the capsid proteins of other parvoviruses play a prominent role in the determination of viral pathogenicity and host range, we decided to examine the relationship between the capsid protein sequences and pathogenicity of ADV. Comparison of the ADV-TR hypervariable region sequence with sequences of other isolates of ADV revealed that ADV-TR was 94 to 100% related to the nonpathogenic type 1 ADV-G at both the DNA and amino acid levels but less than 90% related to other pathogenic ADVs like the type 2 ADV-Utah, the type 3 ADV-ZK8, or ADV-Pullman. This finding indicated that a virus with a type 1 hypervariable region could be pathogenic. To perform a more comprehensive analysis, the complete VP2 sequence of ADV-TR was obtained and compared with that of the 647-amino-acid VP2 of ADV-G and the corresponding VP2 sequences of the pathogenic ADV-Utah, ADV-Pullman, and ADV-ZK8. Although the hypervariable region amino acid sequence of ADV-TR was identical to that of ADV-G, there were 12 amino acid differences between ADV-G and ADV-TR. Each of these differences was at a position where other pathogenic isolates also differed from ADV-G. Thus, although ADV-TR had the hypervariable sequence of the nonpathogenic type 1 ADV-G, the remainder of the VP2 sequence resembled sequences of other pathogenic ADVs. Under experimental conditions, ADV-TR and ADV-Utah were highly pathogenic and induced typical AD in trios of both Aleutian and non-Aleutian mink, whereas ADV-Pullman was pathogenic only for Aleutian mink and ADV-G was noninfectious. Trios of raccoons experimentally inoculated with ADV-TR and ADV-Utah all became infected with ADV, but only a single ADV-Pullman-inoculated raccoon showed evidence of infection. Furthermore, none of the ADV isolates induced pathological findings of AD in raccoons. Finally, when a preparation of ADV-TR prepared from infected raccoon lymph nodes was inoculated into mink and raccoons, typical AD was induced in Aleutian and non-Aleutian mink, but raccoons failed to show serological or pathological evidence of infection. These results indicated that raccoons can become infected with ADV and may have a role in the transmission of virus to mink but that raccoon-to-raccoon transmission of ADV is unlikely.

Aleutian Mink Disease↗

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↗