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PubMed1997

Nucleotide sequence of the P1 region of foot-and-mouth disease virus strain O1 Caseros.

It has been shown that variation of antigenic site I in VP1 of foot-and-mouth disease virus (FMDV) plays an important role in the antigenic diversification of this virus. However, the O1 Campos strain is able to efficiently cross-protect cattle against the O1 Caseros strain, despite having a different sequence in the site I. In this paper we report and compare the P1 coding region for the capsid proteins of FMDV O1 Caseros and O1 Campos. The deduced amino acid sequence showed a total of 31 amino acid differences. Eight of them are located in surface-exposed loops that have been implicated in antigenic sites. This study should help to identify additional sites to be considered in the development of a new generation of FMDV vaccines.

Amino Acid Sequence↗

PubMed1979

Partial purification of tumour-specific transplantation antigens from methylcholanthrene-induced murine sarcomas by immobilized lectins.

Plasma membranes isolated from two immunogenic, non-cross-protecting, MC sarcomas were shown to retain the specific rejection antigens of whole cells as well as serologically detected H-2 antigens. Solubilization of the membranes with sodium deoxycholate gave quantitative release of H-2 and retained the rejection specificity of the tumour from which it was derived. Polyacrylamide-gel electrophoresis (PAGE) showed no extensive degradation of membrane components during solubilization. The solubilized TSTAs were further characterized and purified on columns of 4 different lectins immobilized on sepharose beads. TSTA from both tumours bound to WGA but not to Con A, LCH or RCA columns. Specific activity was retained after elution from the WGA column. Serologically detectable H-2 bound to the Con A and LCH columns only. Clear separation of H-2 from TSTA activity was thus obtained. Furthermore the WGA-binding material represents a source for further purification of TSTA molecules in order to explore the basis for their diversity.

Animals↗

PubMed1993

Recombinant vaccines against ovine footrot.

For the past 20 years footrot vaccines have evolved from simple bacterins to highly specific recombinant DNA (rDNA) fimbrial vaccines. The development of these vaccines has left a trail of discoveries, challenges and solutions; these processes continue as we move closer to understanding the requirements of a footrot vaccine. The initial whole cell vaccines were unsuccessful due to the short duration of immunity and incorporation of limited serotypes. A multistrain vaccine eliminated the problem of serotype inclusion, although the duration of immunity in many cases is still inadequate. The proteases of Dichelobacter nodosus appear to be cross protective; however, little is known of their ability to protect sheep against footrot. The major protective immunogen is the bacterial fimbriae, which also forms the basis for the K-agglutination serotyping system. K-agglutinin titre correlates directly with resistance to challenge. The protective fimbrial epitope is conformationally dependent, suggesting little advantage in the development of synthetic peptide vaccines. To enhance the efficiency of vaccine production D. nodosus fimbrial genes were eventually cloned and successfully expressed in Ps. aeruginosa. Monovalent vaccines based on recombinant fimbriae are omnipotent, inducing high levels of agglutinins and long lasting immunity. In multivalent vaccines, on the other hand, incorporation of each additional serogroup into the vaccine results in reduced efficacy both in terms of reduced K-agglutinin titres and reduced protection following challenge. The least effective are multivalent formulations representing all major serogroups. In addition, considerable genetic variation has been observed in the ability of sheep to respond optimally to each serogroup in a multivalent vaccine. Results show that the limitation of the sheep to mount an effective immune response, rather than the quality or quantity of the immunogen, limits the efficacy of current footrot vaccines. Studies are being undertaken to examine in detail the immune response of sheep to potentially highly effective footrot vaccines.

Animals↗

PubMed1997

Nitric oxide and superoxide induced p53 and Bax accumulation during mesangial cell apoptosis.

During proliferative glomerulonephritis, the early phase of mesangiolysis is linked to increased nitric oxide (NO) production. NO. as well as superoxide (O2-) are inflammatory mediators that are generated by mesangial cells (MC) after cytokine stimulation. Added individually, both radicals induce MC apoptosis. However, the co-existence of a defined NO./O2- ratio is cross-protective. Apoptosis is characterized by specific features such as chromatin condensation, DNA strand breaks, and the occurrence of apoptotic regulating proteins. The tumor suppressor p53 and Bax (Bcl-2 associated protein x) are considered to be classical death promotors, which accumulate after toxic insults. To study p53 and Bax protein accumulation in NO. and/or O2(-)-induced apoptosis, we used the NO-donor S-nitrosoglutathione (GSNO) and the redox cycler 2,3-dimethoxy-1,4-naphtoquione (DMNQ). Both agonists initiated DNA fragmentation in a concentration dependent manner associated with transient p53 and Bax up-regulation. Co-generation of NO./O2- resulted not only in reduced DNA fragmentation, but also in decreased Bax accumulation. Comparable to the NO./O2- co-generation, cytokines failed to induce apoptosis. In contrast, cytokines in combination with pyrrolidine dithiocarbamate, which blocks endogenous superoxide dismutase, allowed p53 and Bax accumulation as well as DNA fragmentation. Our results demonstrate p53 and Bax as early components in NO. and O2(-)-induced rat MC apoptosis and point to the NO./O2- interaction as a naturally occurring cell defense mechanism.

Animals↗

PubMed2001

Heat and salt stress in the food pathogen Bacillus cereus.

AIMS: The effects of stresses imposed on bacterial contaminants during food processing and treatment of packaging material were evaluated on the food pathogen Bacillus cereus. METHODS AND RESULTS: Conditions were established which allowed the cells to adapt to heat, ethanol and hydrogen peroxide stresses, but not to osmotic shock. Cross protection between stresses indicated a clear hierarchy of resistance with salt protecting against hydrogen peroxide, which protected against ethanol, which protected against heat shock. The cultures were shown to be most sensitive to heat, ethanol and oxidative stress at mid-exponential phase and to become resistant at stationary phase. Adaptive levels of stressor were found to induce synthesis of general stress and stress-specific proteins and differential accumulation of proteins was demonstrated between heat- or salt-stressed and unstressed cells. CONCLUSIONS: Sequencing revealed that a number of glycolytic enzymes were regulated by heat and osmotic shocks and that the chaperone GroEL was induced by heat shock. SIGNIFICANCE AND IMPACT OF THE STUDY: The implications of the physiological data in designing storage and processing conditions for food are discussed. The identification of stress-regulated proteins reveals a clear role for glycolysis in adaptation to heat shock and osmotic stress.

Amino Acid Sequence↗

PubMed2003

Control of rpoS transcription in Escherichia coli and Pseudomonas: why so different?

In Escherichia coli, the stationary phase alternative sigma factor sigmas controls the expression of genes involved cell survival in response to cessation of growth (stationary phase) and provides cross-protection to various stresses. Levels of sigmas increase dramatically at the onset of stationary phase and are regulated at the transcriptional, post-transcriptional and post-translational level, making this one of the most complex regulatory systems in bacteria. The basic mechanisms for the control of translation and sigmas proteolysis have been understood. However, studies on the transcriptional control in E. coli lag behind and are controversial. The cAMP-CRP complex and the two component BarA/UvrY system have been implicated and, ppGpp and polyphosphate appear to have a signalling role. sigmas has also been reported to be a general stress regulator in the fluorescent pseudomonads (Pseudomonas aeruginosa, P. fluorescens and P. putida) and recent studies on sigmas regulation highlight that transcriptional regulation in these bacteria apparently plays a major role. Global regulatory systems, the GacA/GacS two component system and quorum sensing all affect rpoS expression, as does the TetR family PsrA regulator that directly binds to- and activates the rpoS promoter in stationary phase. This striking difference in regulation between E. coli and Pseudomonas can be partly attributed to the differences in the functional role of sigmas in the two bacterial species. This report will review mainly recent studies on rpoS transcriptional regulation and will try to rationalize the current knowledge into a working model.

Bacterial Proteins↗

PubMed2003

Vaccination against Fasciola hepatica infection using a Schistosoma mansoni defined recombinant antigen, Sm14.

Fasciola hepatica is the causative agent of fasciolosis in many areas in America, Europe, Africa, Asia and Australia. There is an urgent need for improved methods to control the parasite's transmission. We describe the use of an experimental vaccine based on a recombinant antigen cloned from another parasite, Schistosoma mansoni (Sm14), that induces high levels of cross protection in mice against both S. mansoni and F. hepatica. Sheep and mice vaccinated with Sm14 were significantly protected against challenge infection with metacercariae of Fasciola hepatica and were completely free of the histopathological hepatic damage related to liver fluke infection. The vaccine will provide a valuable new tool to aid in transmission control of this economically important disease.

Animals↗

PubMed2001

Combined benefits of annual mass treatment with ivermectin and cattle zooprophylaxis on the severity of human onchocerciasis in northern Cameroon.

We studied the effect of 10 annual distributions of ivermectin for control of human onchocerciasis on the reduction of Onchocerca volvulus transmission by Simulium vector flies. Prevalence and infection load in the human population decreased, whilst the annual biting rates (ABR) of the vector remained unchanged. The annual transmission potential of infective larvae of O. volvulus fell to 40% of the pre-intervention level, but was still sufficient to maintain endemicity. However, recent immigration of herds of nomadic cattle into the study area has diverted the flies from man to cattle, creating an additional zooprophylactic effect. The predominant transmission of the bovine filaria O. ochengi to man also provides some concomitant cross-protective immunity against further infestations with O. volvulus. The effects of ivermectin on O. volvulus, combined with the zooprophylactic effects of the increased cattle population, have produced a complex beneficial influence on the transmission of human onchocerciasis.

Animals↗

PubMed2000

Avian pneumovirus infections of turkeys and chickens.

Avian pneumoviruses (APVs) cause major disease and welfare problems in many areas of the world. In turkeys the respiratory disease and the effect on egg laying performance are clearly defined. However, in chickens, the role of APV as a primary pathogen is less clear, although it is widely believed to be one of the factors involved in Swollen Head Syndrome. The mechanisms of virus transmission over large distances are not understood, but wild birds have been implicated. APV has recently been reported in the USA for the first time and the virus isolated was a different type or possibly a different serotype from the APVs found elsewhere. Good biosecurity is crucial for controlling infection and highly effective vaccines are available for prophylaxis. Although different subtypes and possibly different serotypes exist, there is good cross protection between them. Diagnosis is usually based on serology using ELISAs, but the available kits give variable results, interpretation is difficult and improved diagnostic tests are required.

Animal Welfare↗

PubMed2002

Heterologous transmission with Dictyocaulus capreolus from roe deer (Capreolus capreolus) to cattle (Bos taurus).

Eight Swedish Red Breed cattle, about 2 months old, were experimentally infected with a Swedish isolate of Dictyocaulus viviparus (Dviv-Se) from cattle and D. capreolus from roe deer. The aims were to determine whether the roe deer lungworm is infective to cattle or if it can induce seroconversion in cattle against D. viviparus as measured with an ELISA. Four calves which were given 500 Dviv-Se infective larvae (L3) each by larval dosing for two successive days developed patent infection between days 23 and 25 post-inoculation (PI). Larval output varied among the calves and during the patent period. However, maximum recovery occurred between 28 and 56 days PI with peak shedding on day 37 PI. Shedding ceased at day 58 PI and adult worms were recovered from one calf at necropsy (day 67 PI). No immature worms were recovered from the lungs at necropsy. Seroconversion was detected on days 35-42 PI. One Dviv-Se infected calf became seronegative on day 67 PI whereas the other calves still remained seropositive during this period. Prepatency and patency periods of D. viviparus and serological findings in this study basically conform to previous studies. Each calf that was infected with 400 L3 of D. capreolus for two successive days, and about 800 L3 of the same species about 8 weeks later, did not develop to patency based on faecal and post-mortem examinations. Consequently, under the conditions of this study, D. capreolus was not infective to cattle. Two of the four calves that were infected with L3 from roe deer were challenged with L3 cultured from faeces of the Dviv-Se-infected calves. This infection did not develop to patency. Whether this was due to cross-protection as a result of the prior priming with L3 from roe deer is not clear. However, if it is so, it opens up the possibility of using D. capreolus L3 for preventing bovine dictyocauliasis.

Animals↗

PubMed2006

Resistance against heterogeneous sequential infections: experimental studies with a tapeworm and its copepod host.

Parasite heterogeneity is thought to be an important factor influencing the likelihood and the dynamics of infection. Previous studies have demonstrated that simultaneous exposure of hosts to a heterogeneous mixture of parasites might increase infection success. Here this view is extended towards the effect of parasite heterogeneity on subsequent infections. Using a system of the tapeworm Schistocephalus solidus and its copepod intermediate host, heterogeneity of the tapeworm surface carbohydrates is investigated, i.e. structures that are potentially recognized by the invertebrate host's immune system. With lectin labelling, a significant proportion of variation in surface carbohydrates is related to differences in worm sibships (i.e. families). Tapeworm sibships were used for experimental exposure of copepods to either homogeneous combinations of tapeworm larvae, i.e. worms derived from the same sibship or heterogeneous mixtures of larvae, and copepods were subsequently challenged with an unrelated larva to study re-infection. Contrary to expectation, neither an effect of parasite heterogeneity on the current infection, nor on re-infection were found. The effect of parasitic heterogeneity on host immunity is therefore complex, potentially involving increased cross-protection on the one hand, with higher costs of raising a more heterogeneous immune response on the other.

Animals↗

PubMed1977

The nature of immunity against Babesia hylomysci and B. microti infections in mice.

Mice which have recovered from Babesia microti infection lose their parasitaemia as soon as three weeks after recovery and become solidly immune. This sterile immunity is not affected by splenectomy and may last for the life of the mouse. Mice which have recovered from B. hylomysci infection continue to harbour parasites at a subpatent level and spontaneous relapses were common after recovery. Hence the type of immunity which developed against this parasite is premunition and may last for life. Such immunity was not absolute and considerable parasitaemias developed after challenge. Cross-protection occurred between the two species of parasite.

Animals↗

PubMed1998

Do babesiosis and malaria share a common disease process?

Clinical Confusion between human babesiosis and malaria is often reported in the literature. Headache, fever, chills, nausea, vomiting, myalgia, altered mental status, disseminated intravascular coagulation, anaemia with dyserythropoiesis, hypotension, respiratory distress, and renal insufficiency are common to both diseases. This remarkable similarity is not restricted to the human host. In the mouse, for example, the histological changes wrought by fatal malaria (Plasmodium vinckei) and babesiosis (Babesia rhodaini) are identical, and parasites of both genera cross-protect. Malarial disease pathogenesis is now generally associated with excessive production of pro-inflammatory cytokines , such as tumour necrosis factor. While this concept has not yet been examined in babesiosis, indirect evidence arises from noting the parasite density at which illness occurs in primary infections caused by either organism. Naive mice tolerate high loads of malarial or babesial parasites before they become ill, and are also tolerant to endotoxicity, which is mediated by these same cytokines. In contrast, humans require very much smaller loads of Plasmodium or Babesia spp. before becoming ill, and likewise are very sensitive to endotoxin, the harmful effects of which are mediated by the pro-inflammatory cytokines. For these reasons, as discussed in this review, the diseases caused by these two genera of intra-erythrocytic protozoan parasites will probably prove to be conceptually identical.

Animals↗

PubMed1986

Investigation into the pathogenesis of atrophic rhinitis in pigs. I. Atrophic rhinitis caused by Bordetella bronchiseptica and Pasteurella multocida and the meaning of a thermolabile toxin of P. multocida.

In two groups of swine herds, herds with and without clinical AR the presence of Atrophic Rhinitis (AR) correlated with the presence of toxinogenic Pasteurella multocida (PM) and not with the Bordetella bronchiseptica (BB) infection. Six BB- and eighteen PM-strains have been investigated for AR pathogenicity. Broth cultures were injected intradermally in guinea-pigs (GPST) or intranasally in 3-week-old colostrum deprived specific pathogen free (SPF) piglets. The average atrophy of the ventral conchae (AVC) correlated with the GPST in 4 BB-and 7 PM-strains. One BB- and 2 PM-strains were qualified as doubtful, the others as non-AR pathogenic. With AR pathogenic BB-and PM-strains clinical AR could be induced in 3-and 6-week-old piglets. AVC lesions (gradation greater than 1) could be induced with BB in piglets of 6 and with pathogenic PM in 16-week-old piglets. Six of seven AR pathogenic PM-strains resembled Carter-type D and one resembled type A. No significance was found between AR pathogenicity and somatic serotypes. Intranasal instillations of cell-free broth culture filtrates of AR pathogenic PM-strains also caused AR in piglets. These filtrates also caused lethality in piglets and in mice lethalitytest (MLT) and induced a positive GPST. After heating the pathogenic effects of the filtrates disappeared. The name AR toxin has been introduced for this thermolabile, haemorrhagic dermonecrotic (HDNT) fraction of the AR inducing filtrates. The severity of the AR lesions depended on the amount of the AR toxin intranasally instilled in pigs. Cross protecting antibodies obtained in rabbits against the AR toxins of two PM strains could be demonstrated by a toxin neutralisation test in the MLT and the GPST. Broth cultures were injected intradermally in guinea-pigs (GPST) or intranasally in 3-week-old colostrum deprived specific pathogen free (SPF) piglets.

Age Factors↗

PubMed2005

S1 gene characteristics and efficacy of vaccination against infectious bronchitis virus field isolates from the United States and Israel (1996 to 2000).

The S1 genes of isolates of avian coronavirus infectious bronchitis virus (IBV) from commercial chickens in the US and Israel (20 isolates from each country) were studied using reverse transcription-polymerase chain reaction restriction fragment length polymorphism and sequencing. Partial sequences spanning the amino terminus region of S1 from amino acid residues 48 to 219, based on the Beaudette strain, were used for analysis. Phylogenetic clustering and high-sequence identity values were used to identify isolates that appeared to be derived from live IBV vaccines used in the two countries. Novel variant strains, unrelated by S1 sequencing and restriction fragment length polymorphism analyses to reference and vaccine strains, were also identified. Based on S1 sequence identity to available vaccines, the potential to use vaccination to control IBV infections was evaluated. Vaccination with commercial live strains Massachusetts (Mass), Arkansas (Ark) or DE/072/92, generally produced immunity against vaccine-related field isolates displaying high S1 sequence similarities (> or = 90%) to the respective vaccine strains. Immunization with a bivalent vaccine containing the Mass and Ark strains provided good cross-protection, averaging 81% against challenge with five variant isolates from the US having amino acid identity values ranging from 62 to 69% to Mass and from 68 to 83% to Ark, respectively. In contrast, the H120 vaccine strain induced low levels of protection, ranging from 25 to 58% against variant field isolates from Israel with amino acid identity values from 65 to 67%.

Animals↗

PubMed2000

Diversity and prevalence of PorA types in Neisseria meningitidis serogroup B in the United States, 1992-1998.

Two hundred eighty-one sporadic Neisseria meningitidis serogroup B isolates, collected through active laboratory-based surveillance, were selected to be analyzed by PorA variable region (VR) typing to determine the prevalence of PorA types in the United States. A substantial number of distinct VR types were identified, 31 in VR1 and 41 in VR2. A total of 73 different PorA types were found, and 76. 7% of these types comprise nonprototype sequences in VR1, VR2, or both. The most prevalent PorA types were P1.7,16-20 (previously P1.7, 16i), P1.22,14, P1.22-1,14 (previously P1.22a,14), P1.7,16, P1.7-1,1 (previously P1.7d,1), P1.19,15, and P1.17,16-3 (previously P1.B,16d). No correlation was observed between the PorA types and geographic origin of the isolates. These data may aid in the design of an efficacious outer membrane protein-based vaccine by identifying the most appropriate PorA types for vaccine formulation. Studies are needed to fully evaluate the extent of cross-protection in humans among the variants and prototypes in each PorA VR family.

Centers for Disease Control and Prevention, U.S.↗

PubMed2004

Frequent hepatitis C virus superinfection in injection drug users.

The frequency of hepatitis C virus (HCV) superinfection with a divergent viral strain was determined in a cohort of recently infected young injection drug users (IDUs) with an HCV incidence rate of 25%. HCV was amplified, by use of polymerase chain reaction (PCR), from plasma samples collected from 25 HCV-infected individuals over an average period of 12 months, and their viral sequences were compared. Phylogenetic analysis identified 5 IDUs with superinfection (20%) occurring after seroconversion: 2 IDUs were superinfected with different HCV genotypes, and 3 were superinfected with divergent strains of the same genotype. The superinfecting strains were not detected as minority variants (<0.5%) in the initial plasma HCV quasi species. Extensive measures were taken to exclude PCR contamination and mix-up of samples, and superinfection results were concordant at 2 HCV genetic loci. HCV superinfection in IDUs, both intra- and intergenotype, is therefore a frequent event, with an incidence rate similar to that of de novo infections. These results suggest that no cross-protecting immunity develops during the first year of chronic infection with HCV.

Adult↗

PubMed1997

Characterization and titration of an HIV type 1 subtype E chimpanzee challenge stock.

A subtype E human immunodeficiency virus type 1 (HIV-1) isolate from the Central African Republic (E/90CR402) was adapted to growth on chimpanzee peripheral blood mononuclear cells (PBMCs) by cocultivation of irradiated, infected human PBMCs with chimpanzee PBMCs. The resulting virus was passaged in chimpanzee PBMCs to generate a stock of chimpanzee-adapted virus. Although its V3 region sequence was identical to that of the parental isolate, the chimpanzee-adapted virus had a syncytium-inducing phenotype as opposed to the non-syncytium-inducing phenotype of the parental virus. After demonstrating in one animal each that the passaged virus could infect chimpanzees following intravenous (i.v.) or cervical inoculation, the i.v. infectious titer of the stock was determined. Exposure of three chimpanzees to different doses of the virus indicated that the titer was between 2 and 5 TCID50. Thus, the HIV-1 E/90CR402 chimpanzee challenge stock established persistent infections in chimpanzees by both the i.v. and genital routes and should be valuable for future HIV-1 vaccine studies to evaluate cross-protection between HIV-1 subtypes.

Animals↗