[Experimental study on the effect of Newcastle disease virus on the eye in rabbit].
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Newcastle disease (ND), caused by avian paramyxovirus serotype 1 (APMV-1) viruses, is included in List A of the Office International des Epizooties. Historically, ND has been a devastating disease of poultry, and in many countries the disease remains one of the major problems affecting existing or developing poultry industries. Even in countries where ND may be considered to be controlled, an economic burden is still associated with vaccination and/or maintaining strict biosecurity measures. The variable nature of Newcastle disease virus strains in terms of virulence for poultry and the different susceptibilities of the different species of birds mean that for control and trade purposes, ND requires careful definition. Confirmatory diagnosis of ND requires the isolation and characterisation of the virus involved. Assessments of virulence conventionally require in vivo testing. However, in vitro genetic characterisation of viruses is being used increasingly now that the molecular basis of pathogenicity is more fully understood. Control of ND is by prevention of introduction and spread, good biosecurity practices and/or vaccination. Newcastle disease viruses may infect humans, usually causing transient conjunctivitis, but human-to-human spread has never been reported. Eight other serotypes of avian paramyxoviruses are recognised, namely: APMV-2 to APMV-9. Most of these serotypes appear to be present in natural reservoirs of specific feral avian species, although other host species are usually susceptible. Only APMV-2 and APMV-3 viruses have made a significant disease and economic impact on poultry production. Both types of viruses cause respiratory disease and egg production losses which may be severe when exacerbated by other infections or environmental stresses. No reports exist of natural infections of chickens with APMV-3 viruses.
When Newcastle disease virus (NDV) is treated with NP-40 and ether a membrane fraction of 150,000 m.w. is obtained. This fraction which is composed of two polypeptides with m.w. of 56,000 and 76,000 was used in a radioimmunoassay (RIA). The assay was developed for both antigen and antibody and was found to be reproducible, specific, and highly sensitive. Titers of 1:51,200 were determined by RIA as compared to 1:4 by agar gel diffusion and 1:200 by hemaglutination inhibition (HI). As little as 5 ng of viral protein were detected by RIA inhibition technique. Labeled antigen could be stored in the presence of serum, KCI and Triton X-100 at -20 degrees C for as long as 6 weeks and retained similar reactivity as fresh reagent.
The Newcastle disease virus (NDV) has antineoplastic and immunostimulatory properties, and it is currently clinically tested in anticancer therapy. However, the tumoricidal mechanisms of NDV tumor therapy are not fully understood. The results presented here demonstrate that NDV-stimulated human monocytes (Mphi) kill various human tumor cell lines and that this tumoricidal activity is mediated by TRAIL. In contrast to soluble TRAIL-R2-Fc, soluble CD95-Fc and TNF-R2-Fc showed only minimal blocking of the antitumor effect. TRAIL expression is induced on human Mphi after stimulation with NDV and UV-inactivated NDV. These results show that TRAIL induction on human Mphi after NDV stimulation is independent from viral replication and that TRAIL mediates the tumoricidal activity of NDV-stimulated human Mphi.
Newcastle disease virus (NDV) possesses two envelope spike glycoproteins: the haemagglutinin-neuraminidase (HN) protein and the fusion (F) protein. The HN protein, which is responsible for virus attachment to sialic acid-containing receptors, varies in length due to differences in the sizes of the ORFs. An HN protein precursor of 616 aa has been found in avirulent but not in virulent NDV strains, whereas an HN protein of 571 aa can be detected in highly virulent strains only. An HN protein of 577 aa is present in virulent and avirulent strains. The F protein, which mediates virus-cell fusion, requires proteolytic activation at an internal cleavage site, whose amino acid composition determines cleavability by various proteases. Here, the functional significance of the length of the HN protein in combination with F protein cleavage sites typical for virulent (velogenic and mesogenic) or avirulent (lentogenic) strains was investigated. To this end, site-directed mutagenesis was used to construct recombinant NDV on the basis of an infectious clone of the lentogenic vaccine virus Clone-30. Only recombinant NDV expressing an F protein with a multibasic cleavage site typical of virulent strains was able to spread efficiently in cell culture, irrespective of the size of the HN protein. Moreover, as determined by the intracerebral pathogenicity index (ICPI) in 1-day-old, specific-pathogen-free chickens, pathogenicity was influenced by the cleavability of the F protein and not by the length of the HN protein. The maximum ICPI value obtained for these recombinants was 1.3, as compared to a possible maximum of 2. This demonstrates that the modifications introduced did not result in the conversion of the lentogenic Clone-30 to a velogenic strain with an ICPI value of >1.5 and suggests the involvement of additional virulence determinants that contribute to the pathogenicity of NDV.
The virulent forms of Newcastle disease virus cause a devastating disease of poultry. Between 1998 and 2000, sporadic outbreaks of Newcastle disease occurred in Taiwan despite vaccination. The causes of the failure of the vaccination remain unclear. The purpose of this study was to investigate the possible factors causing these outbreaks by serologic and virologic methods. Anti-Newcastle disease virus hemagglutination-inhibition titers were measured for serum samples obtained from a breeder farm and a broiler farm. The serologic data showed continued presence of virulent Newcastle disease viruses in the field during inter-outbreak periods. Phylogenetic analysis demonstrated that the field virulent Newcastle disease viruses were genetically similar and were grouped into genotype VIIa. Efficacy testing by virulent Newcastle disease virus challenge revealed that the vaccines used were effective for protecting chickens from infections. This investigation demonstrated that the Newcastle disease virus strain can spread quickly and widely throughout a large geographic area, and that the sporadic cases originate from virulent Newcastle disease viruses present in the field.
Experimental infection with infectious bursal disease virus (IBDV) at hatching or at 3 weeks of age in White Leghorn chickens without maternally derived antibodies to IBDV resulted in a depression in the antibody response of chickens to Newcastle disease vaccination (NDV) at 4 weeks of age and increased the susceptibility of those birds to challenge with virulent NDV. Infection of non-IBDV immune chickens with IBDV at hatching, but not at 3 weeks of age, also depressed the antibody response of chickens vaccinated at 18, 30, or 42 weeks of age, but had no effect on the susceptibility of those birds to challenge with virulent NDV. Prior exposure to IBDV did not alter disease resistance afforded a bird by NDV vaccination at 18, 30, or 42 weeks of age. However, IBDV infection at hatching did render chickens that were not vaccinated against ND more susceptible to challenge with virulent NDV at 21, 33, or 45 weeks of age than unvaccinated birds which were not infected with IBDV or unvaccinated chickens infected with IBDV at 3 weeks of age.
A Newcastle disease virus lysate of malignant melanoma cells was examined for its possible value in delaying the progression of malignant melanoma with palpable regional node disease (Stage II) to disseminated melanoma (Stage III). This Phase II study was carried out in a group of 32 patients following therapeutic lymphadenectomy. The patients were not prospectively randomized. In each patient, the viral oncolysate was administered subcutaneously at regular intervals over 3 years. The cumulated progressions to disseminated disease at 1, 2 and 3 years were 6%, 8% and 12% of the study group, respectively. These experienced losses were considerably lower than in the control group and in similar control groups described by other investigators. The results suggest that an oncolysate prepared with Newcastle disease virus is a helpful adjunct to surgery in the management of Stage II malignant melanoma.
Living V4 strain Newcastle disease vaccine was given to chickens orally. The inclusion of DEAE-dextran, Quil-A or TiterMax in the vaccine, or delivering the vaccine as Iscoms, did not enhance the serological response. The immediate serological response to living V4 vaccine was enhanced in the presence of Avridine. Chickens produced a low serological response to oral administration of inactivated V4 vaccine. This response was not enhanced in the presence of Avridine.
Vaccination for Newcastle disease (ND) is routinely practised in countries where virulent strains of the Newcastle disease virus (NDV) are endemic and in countries where virulent strains do not exist but ill-timed infection by a low virulent field strain may have significant economic consequences for the producer. The types of vaccines and vaccination schedules used vary depending on the potential threat, virulence of the field challenge virus, type of production, and production schedules. A combination of live and inactivated ND vaccine, administered simultaneously, is shown to provide better protection against virulent NDV and has been successfully used in control programmes in areas of intense poultry production. A potential limiting factor in the use of live vaccines to control virulent ND is that live virus can interfere with surveillance and laboratory diagnosis. However, a new assay, the real-time reverse transcriptase-polymerase chain reaction (RRT-PCR), differentiates low virulent from virulent NDV, thus minimizing the disadvantage of live virus vaccines in the face of an outbreak and may facilitate the use of such vaccines to control outbreaks of virulent ND in the future.
A virulent Newcastle disease virus (NDV) isolate from an outbreak in commercial poultry, with virulence indices of MDT = 47-48 h; IVPI = 2,17 and ICPI = 1,8; was used to inoculate 10x vaccinated (standard poultry vaccines) as well as 10x unvaccinated slaughter ostriches via intratracheal, ocular and nasal routes, in a controlled environment. All unvaccinated ostriches developed clinical signs (mainly respiratory); two of them died while the other eight recovered. No vaccinated ostriches developed any clinical signs. All remaining (18) ostriches were slaughtered 14 d after the last mortality. Virulent NDV could be re-isolated from the dead birds, but not from organs, muscle (fresh), muscle (24 h chilled), gastro-intestinal tract, bone-marrow or respiratory system taken from the slaughtered ostriches. It is suggested that it would be extremely unlikely that the international trade in ostrich meat could act as a mechanism for spreading virulent NDV from endemic to non-endemic parts of the world.
Twelve isolations of Newcastle disease virus were made from 77 clinical samples from chickens from conjunctivitis, respiratory disease, proventriculitis and bursal atrophy. Nine of the isolations were made from chickens with conjunctivitis. The viruses were identified as Newcastle disease virus by inhibition of their haemagglutinins with specific antiserum to Newcastle disease virus. The viruses failed to kill chicken embryos after inoculation into the allantoic cavity and they were judged to be lentogenic strains. There was no evidence that the Newcastle disease viruses were responsible for any of the clinical conditions from which they were isolated. The presence of other agents in 10 of the samples was indicated by reduced production of haemagglutinin in allantoic fluids of infected embryos, by deaths of infected embryos, by the production of cytopathic changes in avian cell cultures and by electron microscopy. Three isolations of infectious bronchitis virus, 2 of avian adenovirus and one of avian reovirus were made. Other samples were suspected of containing infectious bronchitis virus and mycoplasmas, but these were not isolated. The Newcastle disease viruses failed to produce plaques in chicken embryo fibroblast cell cultures and they were separated from the contaminating agents by haemagglutination and elution followed by passage at terminal dilution in chick embryos. No Newcastle disease virus was isolated from 60 caecal tonsils and 60 lung samples from 9-week-old broiler chickens. Eight lung samples yielded mycoplasmas that caused haemadsorption in chicken cell cultures. The mycoplasmas were probably Mycoplasma gallisepticum.
A case of Newcastle disease virus infection in a female laboratory technician is reported for the first time in Malaysia. Infection was acquired by droplet infection of the eye while grinding infected chicken in the laboratory. The case was confirmed by isolation of Newcastle disease virus from an eye swab taken from the subject on the first day of clinical signs. A four-fold rise of haemagglutination-inhibition titre was shown when sera on the third day of infection and 15 days later were compared.
The transmission of Newcastle disease virus strains from infected to direct-, indirect-, and aerosol-contact groups of chickens was studied. Chickens 7, 21, and 63 days old were used in separate trials. Chicken age and virus strain were found to be important in spread of the virus. Strain V4 spread quickly to all contact groups and was classed as highly transmissible, whereas strain JA failed to infect all contact chickens of each age group, thus spreading less efficiently than strain V4. The viruses spread more readily among the 2 older groups. The significance of the transmissibility of Newcastle disease virus vaccine is briefly discussed.
The B1 strain of Newcastle disease virus (NDV-B1), which is nonpathogenic for newly hatched chickens, killed embryos when it was used to inoculate chicken eggs at embryonation day 18. Treatment of NDV-B1 with an alkylating agent, ethylmethane sulfonate (EMS) markedly reduced the pathogenicity of the virus for 18-day-old chicken embryos. Eggs inoculated with the modified virus (NDV-B1-EMS) hatched, and the virus was isolated from lungs and spleen of 1-day-old chickens. The hatched chickens developed antibody to NDV and were protected against challenge exposure (at 4 weeks of age) with a highly virulent GB-Texas strain of NDV. Presence of maternal antibody to NDV in embryonating eggs did not influence the protective ability of NDV-B1-EMS, which also induced protective immunity when administered to 4-week-old chickens. The 50% protective dose of NDV-B1-EMS in maternal antibody-negative and -positive embryos was calculated to be 10.77 and 17.70 embryo 50% lethal doses, respectively. Results of the study indicated that NDV-B1-EMS may be used as an embryo vaccine to protect chickens against Newcastle disease.
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