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1.
    

Background

Primary ciliary dyskinesia (PCD) is generally a recessively inherited disorder characterized by dysfunction of motile cilia. A mutation in a new causative gene (CCDC39) has been identified in the Old English Sheepdog (OES).

Objectives

To describe the clinical findings and the molecular changes of affected dogs and estimate the worldwide prevalence of the mutation in a large cohort of OES.

Animals

578 OES, including 28 affected and 550 clinically healthy dogs.

Methods

This retrospective study reviewed the data of OES diagnosed with PCD and OES tested for the mutation. Clinical data including results of physical examination and further investigations were obtained on 11/28 dogs. CCDC39 expression was assessed by qRTPCR and Western blot analysis in affected dogs and healthy dogs. DNA was extracted on 561/578 dogs and a genetic test by Taqman technology was developed to genotype the CCDC39 mutation in these dogs.

Results

Clinical findings were recurrent nasal discharge and cough, pyrexia, leucocytosis, and bronchopneumonia. Ultrastructural defects were characterized by central microtubular abnormalities and decreased number of inner dynein arms (IDAs). Molecular analysis revealed a reduced expression of CCDC39 RNA and an absence of CCDC39 protein in affected dogs compared to healthy dogs. The mutation was more frequent in nonrandomly selected European OES population with a higher proportion of carriers (19%) compared to non‐European dogs (7%).

Conclusion and Clinical Importance

CCDC39 mutation is dispersed in a worldwide population and is responsible for PCD in this breed. Genetic testing might enable control of this disease.  相似文献   

2.
A prospective cohort study was used to assess whether Salmonella fecal shedding in commercial feedlot cattle treated with antimicrobials for respiratory disease was associated with subsequent adverse health outcomes. Feces were collected per rectum from cattle that were examined for apparent respiratory disease, had a rectal temperature > or = 40 degrees C, and subsequently received antimicrobial treatment. Salmonella were recovered from 918 (73.7%) of 1 245 fecal samples and weekly prevalence estimates ranged from 49 to 100% over the 3-month study. Genotypic and phenotypic characteristics of Salmonella strains in the population were determined. Serogroup E Salmonella were most common (73.3%), followed by C1 (11.0%), C3 (8.6%), and B (1.1%). Predominant serotypes were Orion (46.5%), Anatum (19.8%), Kentucky (8.7%), Montevideo (7.5%), and Senftenberg (4.9%). Few isolates (36/918) were positive for antimicrobial resistance-associated integron gene intI1. Phenotypic susceptibility was associated with isolate intI1 status. Crude re-pull, re-treatment and case fatality risks were higher for cattle that were Salmonella-positive versus -negative at initial treatment, but not statistically different on multivariable analysis. However, case fatality risk was higher for cattle shedding Group B Salmonella than for cattle shedding other serogroups. Lots (groups) with a higher Salmonella prevalence at first treatment had a higher proportion of mortalities occur in a hospital pen, higher overall re-treatment risks, and were more likely to be sampled later in the study. Results indicate a high prevalence of Salmonella in this population of cattle treated for apparent respiratory disease, but that effects associated with clinical outcomes may depend on the Salmonella strain.  相似文献   

3.
Staphylococcus aureus subsp. anaerobius, a microaerophilic and catalase-negative bacterium, is the etiological agent of abscess disease, a specific chronic condition of sheep and goats, which is characterized by formation of necrotic lesions that are located typically in superficial lymph nodes. We constructed an isogenic mutant of S. aureus subsp. anaerobius (RDKA84) that carried a repaired and functional catalase gene from S. aureus ATCC 12600, to investigate whether the lack of catalase in S. aureus subsp. anaerobius plays a role in its physiological and pathogenic characteristics. The catalase activity had no apparent influence on the in vitro growth characteristics of RDKA84, which, like the wild-type, did not grow on aerobically incubated agar plates. Restoration of catalase activity in RDKA84 substantially increased resistance to H2O2 when analyzed in a death assay. The intracellular survival rates of the catalase-positive mutant RDKA84 in polymorphonuclear neutrophils (PMN) isolated from adult sheep were significantly higher than those of the wild-type, while no differences were found with PMN isolated from lambs. RDKA84 showed significantly lower survival rates in murine macrophages (J774A.1 cells) than the wild-type strains did, whereas, in bovine mammary epithelial cells (MAC-T), no differences in intracellular survival were observed. Interestingly, the virulence for lambs, the natural host for abscess disease, of the catalase-positive mutant RDKA84 was reduced dramatically in comparison with wild-type S. aureus subsp. anaerobius in two experimental models of infection.  相似文献   

4.
    
Mast cells normally are present in equine bronchoalveolar lavage fluid (BALF), but usually represent <2% of all cells in healthy horses. An increased percentage of mast cells has been associated with airway hyperactivity and inflammatory airway diseases, but marked differences are reported between studies in normal and diseased horses. Because an abnormal mast cell count may be of clinical relevance, we compared the ability of a fast Romanowsky method to stain mast cell granules with that of 3 metachromatic stains: automated Romanowsky, May-Grünwald Giemsa, and toluidine blue stains. The BALF cells from 24 horses were studied. A differential cell count was performed blindly on 400 cells. The percentages of mast cells obtained were analyzed by means of repeated-measures analysis of variance and Fischer's PLSD test. The Bland and Altman method was used to assess agreement among stains. The mean percentage of mast cells in BALF was significantly lower with the fast Romanowsky than with the automated Romanowsky, May-Grünwald Giemsa, and toluidine blue stains. With the fast Romanowsky stain, the metachromatic granules of mast cells were not stained, and their identification was based on morphologic criteria. Toluidine blue staining allowed detection of the highest mean percentage of mast cells, but was inadequate for performing a differential cell count on other cell types. In conclusion, fast Romanosky stain may be inadequate for detection of mast cells in equine BALF, whereas automated Romanowsky, May-Grünwald Giemsa, and toluidine blue stains provide metachromatic staining of mast cell granules.  相似文献   

5.
Background: Inflammatory airway disease (IAD) is prevalent in young racehorses during training, being the 2nd most commonly diagnosed ailment interrupting training of 2‐year‐old Thoroughbred racehorses. Hypothesis: That stabling and exercise cause oxidative stress, release of platelet‐activating factor (PAF) and inflammation in airways of Thoroughbred colts. Animals: Colts in breeding farms (NC, n = 45), stabled for 30 days (EC, n = 40), and race trained (EX, n = 34). Methods: Cytological profile and parameters of bronchoalveolar lavage fluid (BALF) related to oxidative stress, bioactivity of the proinflammatory mediator PAF, catalase activity, and alveolar macrophage function. Results: Percentages of neutrophils and eosinophils in the BALF of the EX group were higher (5.4 ± 6.4% versus 0.9 ± 1.2%) than the upper limits for normal horses (3–5%). BALF from the EX group (45.6 ± 2.8 cells/μL of BALF) also displayed significantly (P= .017) higher total nucleated cell count. PAF bioactivity and the total protein concentration in the BALF were higher in the EX group (0.0683 ± 0.076 versus 0.0056 ± 0.007 340 : 380 nm ratio P= .0039, 0.36 ± 0.30 versus 0.14 ± 0.15 mg of proteins/mL of BALF P < .001). Concentration of BALF hydroperoxides was higher in the EC group (104.7 ± 80.0 versus 35.2 ± 28.0 nmol/mg of proteins, P= .013) and catalase activity was higher in the EX group (0.24 ± 0.16 versus 0.06 ± 0.02 μmol H2O2/min/mg of proteins, P= .0021). Alveolar macrophage phagocytosis (P= .048) as well as production of superoxide anion (P= .0014) and hydrogen peroxide (P= .0011) were significantly lower in EX group. Conclusions and Clinical Importance: Further studies should be performed to elucidate the role of PAF in the pathophysiology of IAD. Its presence in bronchoalveolar fluid of young athletic horses makes it a potential therapeutic target to be investigated.  相似文献   

6.
    

Background

Lower expression of secretoglobin and transferrin has been found in the bronchoalveolar lavage fluid (BALF) of a small number of horses with experimentally induced signs of recurrent airway obstruction (RAO) compared to healthy controls.

Hypothesis/Objectives

Secretoglobin and transferrin BALF expression will be similarly decreased in horses with naturally occurring clinical signs of RAO and in horses with experimentally induced clinical signs of RAO as compared to healthy controls and intermediate in horses with inflammatory airway disease (IAD).

Animals

Recurrent airway obstruction‐affected and control horses were subjected to an experimental hay exposure trial to induce signs of RAO. Client‐owned horses with a presumptive diagnosis of RAO and controls from the same stable environments were recruited.

Methods

Pulmonary function and BALF were evaluated from control and RAO‐affected research horses during an experimental hay exposure trial (n = 5 in each group) and from client‐owned horses (RAO‐affected horses, n = 17; IAD‐affected horses, n = 19; healthy controls, n = 5). The concentrations of secretoglobin and transferrin in BALF were assessed using Western blots.

Results

Naturally occurring and experimentally induced RAO horses had similar decreases in BALF transferrin expression, but secretoglobin expression was most decreased in naturally occurring RAO. Secretoglobin and transferrin expression were both lower in BALF of RAO‐affected horses than in IAD‐affected and control horses.

Conclusions and Clinical Importance

Secretoglobin and transferrin expression is decreased in BALF of RAO‐affected horses after both experimental and natural exposure. Secretoglobin and transferrin likely play clinically relevant roles in the pathophysiology of RAO, and may thus be used as biomarkers of the disease.  相似文献   

7.

Background

Omega‐3 polyunsaturated fatty acid (PUFA) may benefit humans and animals with chronic inflammatory diseases.

Hypothesis

Omega‐3 PUFA supplementation improves clinical signs, lung function, and airway inflammation in horses with recurrent airway obstruction (RAO) and inflammatory airway disease (IAD).

Animals

Eight research horses and 35 client‐owned horses.

Methods

A pilot study examined the dose of PUFA that can alter plasma PUFA composition. Then, a randomized, controlled clinical trial was performed in horses with RAO and IAD. Horses were fed a complete pelleted diet with no hay and randomly assigned to 1 of 3 daily treatments for 2 months: 30 or 60 g of the supplement or 30 g of placebo. Clinical signs, lung function, plasma PUFA composition, and bronchoalveolar lavage fluid (BALF) cytology were evaluated. Data were expressed as median (25–75th percentiles). P < .05 was considered significant.

Results

Polyunsaturated fatty acid supplementation resulted in increased plasma docosahexaenoic acid (DHA) that peaked at 4 weeks. Clinical improvement was noted in all horses involved in the clinical trial, but the group that received PUFA had greater improvement in clinical signs (cough score improved 60%), lung function (respiratory effort decreased 48%), and BALF (neutrophils decreased from 23 to 9%) when compared to placebo (cough score improved 33%, respiratory effort decreased 27%, BALF neutrophils increased from 11 to 17%; P < .05).

Conclusions and Clinical Importance

Feeding horses with RAO and IAD a PUFA supplement containing 1.5–3 g DHA for 2 months provides an additional benefit to low‐dust diet.  相似文献   

8.
Salmonellosis is an important zoonotic disease that affects both people and animals. The incidence of reptile-associated salmonellosis has increased in Western countries due to the increasing popularity of reptiles as pets. In Korea, where reptiles are not popular as pets, many zoos offer programs in which people have contact with animals, including reptiles. So, we determined the rate of Salmonella spp. infection in animals by taking anal swabs from 294 animals at Seoul Grand Park. Salmonella spp. were isolated from 14 of 46 reptiles (30.4%), 1 of 15 birds (6.7%) and 2 of 233 mammals (0.9%). These findings indicate that vigilance is required for determining the presence of zoonotic pathogen infections in zoo animals and contamination of animal facilities to prevent human infection with zoonotic diseases from zoo facilities and animal exhibitions. In addition, prevention of human infection requires proper education about personal hygiene.  相似文献   

9.
Infectious upper respiratory disease (IURD) of Thoroughbred racehorses has been a frequent problem (29.6% of incidence) at the Seoul Race Park (Korea). Risk factors for IURD include the season with a high transfer rate (summer and fall), the stabling period (≤ 3 months), and age (2 to 3 years old), suggesting that the movement and new environment may have depressed the immune system of the horses and decreased their ability to respond properly to pathogens. The bacterial strains (n = 98) isolated from IURD horses included Pseudomonas spp., Escherichia coli, Staphylococcus spp., Streptococcus equi subsp. equi and zooepidemicus.  相似文献   

10.
    
Two captive Keel-billed toucans and a Chestnut-mandibled toucan in another zoological garden died suddenlywithout any pre-existing symptoms, and three months later, a Japanese squirrel died of diarrhea. All theseanimals showed necrotic enteritis and multifocal necrosis in the liver and spleen with Gram negative bacilli.The bacilli showed strong positive immunolabeling for Yersinia pseudotuberculosis O4 in theKeel-billed toucans, Y. pseudotuberculosis O2 in the Chestnut-mandibled toucan and Y.pseudotuberculosis O1 in the Japanese squirrel, while Y. pseudotuberculosis 4b, 2band 1b were respectively isolated from the lesions. To our knowledge, this might be the first reported case offatal yersiniosis in a Japanese squirrel in the world as well as in toucans in Japan.  相似文献   

11.
12.
Vibrio vulnificus is the causative agent of primary septicemia, wound infection and gastroenteritis in immunocompromised people. In this study, signature-tagged mutagenesis (STM) was applied to identify the virulence genes of V. vulnificus. Using STM, 6,480 mutants in total were constructed and divided into 81 sets (INPUT pools); each mutant in a set was assigned a different tag. Each INPUT pool was intraperitoneally injected into iron-overloaded mice, and in vivo surviving mutants were collected from blood samples from the heart (OUTPUT pools). From the genomic DNA of mixed INPUT or OUTPUT pools, digoxigenin-labeled DNA probes against the tagged region were prepared and used for dot hybridization. Thirty tentatively attenuated mutants, which were hybridized clearly with INPUT probes but barely with OUTPUT probes, were negatively selected. Lethal doses of 11 of the 30 mutants were reduced to more than 1/100; of these, the lethal doses of 2 were reduced to as low as 1/100,000. Transposon-inserted genes in the 11 attenuated mutants were those for IMP dehydrogenase, UDP-N-acetylglucosamine-2-epimerase, aspartokinase, phosphoribosylformylglycinamidine cyclo-ligase, malate Na (+) symporter and hypothetical protein. When mice were immunized with an attenuated mutant strain into which IMP dehydrogenase had been inserted with a transposon, they were protected against V. vulnificus infection. In this study, we demonstrated that the STM method can be used to search for the virulence genes of V. vulnificus.  相似文献   

13.
    
A simple random survey was conducted in Ireland during 2005 to estimate the ELISA-prevalence of paratuberculosis, commonly called Johne's disease (JD), in the cattle population. Serum samples were collected from all 20,322 females/breeding bulls over 12 months-of-age in 639 herds. All samples were tested using a commercially available absorbed ELISA. The overall prevalence of infected herds, based on the presence of at least one ELISA-positive animal, was 21.4% (95% CI 18.4%-24.9%). Herd prevalence levels amongst dairy herds (mean 31.5%; 95% CI: 24.6%, 39.3%) was higher than among beef herds (mean 17.9%; 95% CI: 14.6%-21.8%). However, the animal level prevalence was similar. The true prevalence among all animals tested, was calculated to be 2.86% (95%CI: 2.76, 2.97) and for animals >= 2 yrs, it was 3.30% (95%CI: 3.17, 3.43). For animals in beef herds, true prevalence was 3.09% (95%CI: 2.93, 3.24), and for those in dairy herds, 2.74% (95%CI: 2.59, 2.90). The majority of herds had only one ELISA-positive infected animal. Only 6.4% (95% CI 4.7%-8.7%) of all herds had more than one ELISA-positive infected animal; 13.3% (CI 8.7%-19.7%) of dairy herds ranging from two to eight ELISA-positive infected animals; and, 3.9% beef herds (CI 2.4%-6.2%) ranging from two to five ELISA-positive infected animals. The true prevalence of herds infected and shedding Mycobacterium avium subspecies paratuberculosis is estimated to be 9.5% for all herd types; 20.6% for dairy herds; and 7.6% for beef herds. If ELISA positive animals <2-years-of-age are excluded, the true herd prevalene reduces to: 9.3% for all herd types; 19.6% for dairy herds; and 6.3% for beef herds based on a test specificity (Sp) of 99.8% and test sensitivity (Se) (i.e., ability to detect culture-positive, infected animals shedding at any level) of 27.8-28.9%.  相似文献   

14.
    
In a number of countries, tuberculosis (due to infection with Mycobacterium bovis) is a significant health problem of captive deer. This paper describes outbreaks of bovine tuberculosis in sika deer (Cervus nippon) on two farms in Ireland and the methods used to control the disease. On Farm A, infection was first detected during 1993. The infection was eradicated using a programme of test and removal, in association with segregation of young animals. A second outbreak (also due to infection with M. bovis, but a different RFLP profile) was detected in 2002. In the latter outbreak, infection was particularly prevalent in two groups of young deer. M. bovis with the same RFLP profile was also isolated in a badger found dead on the farm. Control was achieved by test and removal in association with herd management changes. In Herd B, infection was first detected in 1995, and subsequently eradicated using test and removal alone. In Herd A, re-infection remains an ongoing risk. Control rather than eradication of infection may more realistic in the short-to medium-term.  相似文献   

15.
Johne''s disease is a condition that refers to chronic granulomatous enteritis in ruminants. It is believed that survival and replication of Mycobacterium (M.) paratuberculosis in mononuclear phagocytes plays an important role in the pathogenesis of Johne''s disease. However, it is not clear how M. paratuberculosis survives for long time periods in mononuclear phagocytes, nor is it clear which factors trigger multiplication of these bacilli and result in the development of Johne''s disease. Investigating the intracellular fate of M. paratuberculosis is challenging because of its very slow growth (more than two months to form visible colonies on media). Existing animal models also have limitations. Despite those obstacles, there has been progress in understanding the intracellular survival tactics of M. paratuberculosis and the host response against them. In this review, we compare known aspects of the intracellular survival tactics of M. paratuberculosis with those of other mycobacterial species, and consider possible mycobactericidal mechanisms of mononuclear phagocytes.  相似文献   

16.
    
Inhalant exposure to airborne irritants commonly encountered in horse stables is implicated in the pathogenesis of inflammatory airway disease (IAD) and recurrent airway obstruction (RAO), non‐infectious, inflammatory pulmonary disorders that impact the health and performance of horses across all equine disciplines. IAD and RAO have overlapping clinical, cytological, and functional manifestations of the pulmonary response to organic dust and noxious gases encountered in the barn environment. Study of these diseases has provided important but incomplete understanding of the effect of air quality upon the respiratory health of horses. In this review, the principles of particulate exposure assessment, including health‐related aerosol size fractions and size‐selective sampling, the factors influencing air quality in equine environments, and the effect of air quality on the equine respiratory tract are discussed. The objective of this review is to provide the reader with a summary of the most common chronic inflammatory airway diseases in the horse and the principles of air sampling that are essential to the planning, interpretation, and assessment of equine respiratory health‐related exposure studies.  相似文献   

17.

Background

Thirteen red deer (Cervus elaphus), culled from the isolated population at the Mongstad Oil Refinery, Norway, were investigated for gastrointestinal helminths. These animals, enclosed by the refinery fence, do not have contact with other ruminants and have a high population density considering the available browsing area (1 km2) within the refinery site (3 km2). The population was estimated to be 110-130 at the time of culling.

Results

The helminth fauna among these sampled red deer was enumerated and species were identified based on morphology. Ostertagia leptospicularis/O. kolchida was detected in 83% [CI 55 - 95%], Spiculopteragia spiculoptera/S. mathevossiani in 92% [CI 65 - 99%] and Trichostrongylus axei in 42%, [CI 19 - 68%] of the abomasa examined. Characterisation of the intestinal parasite fauna revealed Capillaria bovis, Cooperia oncophora, Oesophagostomum venulosum, Trichuris globulosa and tapeworm fragments (presumed anoplocephalids) in seven individuals. Only one calf had an infection with more than one intestinal helminth (tapeworm fragment and Trichuris globulosa). The remaining six deer had single species intestinal infections.No significant age related trends were seen, with the exception of higher intensity of infection of T. axei in yearlings relative to other age classes. Assessment of abomasal parasite burden and body condition revealed no significant trends. In calves, statistically non-significant correlation was seen between increased parasite burden and decreased slaughter weight, whilst the opposite was seen in adults with the heaviest adults exhibiting the higher burdens. Given the small sample size the trends that were seen need further investigation. The parasite burden was aggregated with three adult red deer harbouring 75% of the total abomasal parasite count.

Conclusion

This isolated population was parasitised by a reduced subset of gastrointestinal nematodes typical of this cervid across an extensive geographic range in Eurasia. The intensity and abundance of abomasal nematodes was higher in this isolated population than reported in similar studies of red deer populations across Europe.  相似文献   

18.
The objective of this study was to determine the effects of dietary supplementation with chitooligosaccharide (COS) on growth performance, nutrient digestibility, blood characteristics and immune response in lipopolysaccharide-challenged weanling pigs. A total of 90 crossbred weanling pigs (5.44 ± 0.50 kg BW) were employed in Exp. 1. The three dietary treatments were basal diets supplemented with 0, 2.5, and 5 g COS/kg, and fed for 28 d. Each treatment had 6 replications with 5 pigs per pen. Increasing the level of supplemental COS tended to linearly (P < 0.10) improve ADG and ADFI during phase 2 and overall period, while there were no differences in G:F. The linear improvement in the apparent DM (P < 0.05) and N (P < 0.10) digestibility in pigs fed COS supplemented diets was noticed. The tested blood characteristics were not influenced under non-challenge conditions. In Exp. 2, a total of 20 pigs (5.22 ± 0.31 kg BW) were initially assigned to two dietary treatments and fed basal diets supplemented with 0 or 0.5 g COS/kg for 28 d. At the end of d 28, half of the pigs in each treatment (n = 5) were injected i.p. with Escherichia coli lipopolysaccharide at a concentration of 100 μg/kg of BW. The other half of the pigs in each treatment were injected with sterile saline solution at a concentration of 100 μg/kg of BW. This arrangement resulted in a 2 × 2 factorial design with diet and LPS challenge as the main effects. Blood sample and rectal temperature data were collected at 0, 2, 4 and 12 h post-challenge. Rectal temperatures increased as the result of LPS injection at 4 and 12 h post-challenge (P < 0.05). Serum cortisol, IGF-1, and TNF-α concentration were also increased as the result of LPS challenge (P < 0.05). The COS treatments resulted in lower cortisol concentrations at 2 h and higher IGF-1 concentrations at 4 h post-challenge (P < 0.05). COS and LPS interactions were also observed on cortisol and IGF-1 when the COS effects were presented (P < 0.05). Haptoglobin concentrations remained unaffected throughout the challenge period. White blood cell counts were increased in the LPS-treated pigs at 2 and 4 h post-challenge (P < 0.01). Lymphocyte count was elevated at 2 h and reduced at 12 h post-challenge as the result of LPS challenge (P < 0.05). However, there were no COS main effects observed on lymphocyte count throughout the challenge period. The comparison between two LPS challenged treatments also indicated that COS treatment has beneficial effects on rectal temperature, cortisol and IGF-1 concentrations. In conclusion, dietary supplementation with COS had little effect on nutrient digestibility and inflammatory stress markers in weanling pigs.  相似文献   

19.
    
ABSTRACT: African horse sickness is an economically highly important non-contagious but infectious Orbivirus disease that is transmitted by various species of Culicoides midges. The equids most severely affected by the virus are horses, ponies, and European donkeys; mules are somewhat less susceptible, and African donkeys and zebra are refractory to the devastating consequences of infection. In recent years, Bluetongue virus, an Orbivirus similar to African horse sickness, which also utilises Culicoides spp. as its vector, has drastically increased its range into previously unaffected regions in northern Europe, utilising indigenous vector species, and causing widespread economic damage to the agricultural sector. Considering these events, the current review outlines the history of African horse sickness, including information concerning virus structure, transmission, viraemia, overwintering ability, and the potential implications that an outbreak would have for Ireland. While the current risk for the introduction of African horse sickness to Ireland is considered at worst 'very low', it is important to note that prior to the 2006 outbreak of Bluetongue in northern Europe, both diseases were considered to be of equal risk to the United Kingdom ('medium-risk'). It is therefore likely that any outbreak of this disease would have serious socio-economic consequences for Ireland due to the high density of vulnerable equids and the prevalence of Culicoides species, potentially capable of vectoring the virus.  相似文献   

20.
In this study, specific sequences within three genes (3D, VP4 and 2B) of the foot-and-mouth disease virus (FMDV) genome were determined to be effective RNAi targets. These sequences are highly conserved among different serotype viruses based on sequence analysis. Small interfering RNA (siRNA)-expressing plasmids (p3D-NT19, p3D-NT56, pVP4-NT19, pVP4-NT65 and p2B-NT25) were constructed to express siRNA targeting 3D, VP4 and 2B, respectively. The antiviral potential of these siRNA for various FMDV isolates was investigated in baby hamster kidney (BHK-21) cells and suckling mice. The results show that these siRNA inhibited virus yield 10- to 300-fold for different FMDV isolates of serotype O and serotype Asia I at 48 h post infection in BHK-21 cells compared to control cells. In suckling mice, p3D-NT56 and p2B-NT25 delayed the death of mice. Twenty percent to 40% of the animals that received a single siRNA dose survived 5 days post infection with serotype O or serotype Asia I. We used an attenuated Salmonella choleraesuis (C500) vaccine strain, to carry the plasmid that expresses siRNA directed against the polymerase gene 3D (p3D-NT56) of FMDV. We used guinea pigs to evaluate the inhibitory effects of recombinant S. cho (p3D-NT56/S. cho) on FMDV infection. The results show that 80% of guinea pigs inoculated with 109 CFU of p3D-NT56/S. cho and challenged 36 h later with 50 ID50 of homologous FMDV were protected. We also measured the antiviral activity of p3D-NT56/S. cho in swine. The results indicate that 100% of the animals treated with 5 × 109 CFU of p3D-NT56/S. cho were protected in 9 days.  相似文献   

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