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competitive dna hybridization in microtitre plates for chicken anaemia virus.unlabelled chicken anaemia virus (cav) dna probe, produced by pcr, was immobilized onto nitrocellulose discs that then were fitted into microtitre plate wells in order to develop a competitive, non-radioactive hybridization test for detection of cav. the discs were hybridized with either dna extracts of buffy coats or dilutions of cav dna (for standard curves), followed by hybridization with biotin-labelled cav dna probe in excess of the immobilized, capture probe. thus, cav from sample dna extr ...200111162076
[workshop: immunosuppression in chickens]. 200111194506
evaluation of chicken infectious anemia virus and associated risk factors with disease and production losses in broilers.a case-control study was performed to determine the significance of chicken infectious anemia virus (ciav) as a risk factor associated with secondary disease in commercial broilers and to identify the significance of production losses associated with ciav. the study also examined the relationship between bursal and thymic atrophy and the presence of ciav. cases were defined as submissions to the alabama veterinary diagnostic laboratories with a history of clinical disease and with a diagnosis of ...200011195634
identification of a genetic determinant of pathogenicity in chicken anaemia virus.the molecular basis of pathogenicity of the chicken anaemia virus (cav) needs to be clarified in order to develop a safe, live virus vaccine. in this study, several high- and low-pathogenic infectious dna clones were obtained from field virus samples after 12 or 38 passages in mdcc-msb1 cells. the high-pathogenic clones induced a low haematocrit, low weight gain and high mortality. nucleotide sequence analyses identified one amino acid, at residue 394 of the vp1 capsid protein, as a major determ ...200111297698
coinfection of specific-pathogen-free chickens with marek's disease virus (mdv) and chicken infectious anemia virus: effect of mdv pathotype.both marek's disease virus (mdv) and chicken infectious anemia virus (ciav) infections are prevalent in chickens throughout the world. in the past decade, mdv strains with increased virulence (very virulent plus mdv pathotype [vv+mdv]) have been isolated. the purpose of this experiment was to determine the effects of coinfection of chickens with ciav and a vv+mdv isolate. specific-pathogen-free chickens were inoculated at 1 day posthatch with rb1b (very virulent mdv pathotype [vvmdv]) only, 584a ...200111332504
vertical induction of the inclusion body hepatitis/hydropericardium syndrome with fowl adenovirus and chicken anemia virus.the hypothesis that fowl adenovirus (fav) and chicken anemia virus (cav), transmitted vertically and simultaneously, induce the inclusion body hepatitis (ibh)/hydropericardium (hp) syndrome in progeny chickens was tested. thus, 35-wk-old light brown layer breeders, showing absence of antibodies against fav and variable titers against cav, were intramuscularly singly infected with the fav serotype 4 isolate 341 or dually infected with cav (isolate 10343) and fav. all hens (groups a [fav alone], b ...200111336070
characterisation of a chicken anaemia virus variant population that resists neutralisation with a group-specific monoclonal antibody.a variant population of chicken anaemia virus (cav), termed p310 2a9-resist, that resists neutralisation by the monoclonal antibody (mab) 2a9, was selected from cux-1 virus that had been passaged 310 times (p310) in mdcc-msb1 cells. substantially higher concentrations of mab 2a9 were required to neutralise the selected virus compared to those required to neutralise a low-passage (p13) cux-1 isolate. virus neutralisation tests showed that serum from chickens infected with the p310 2a9-resist viru ...200111402858
genetic characterization of chicken anemia virus from commercial broiler chickens in alabama.chicken anemia virus (cav) isolates show extremely limited genetic variability worldwide. we determined the nucleotide sequence of an 823-nucleotide portion of the 2.3-kb cav genome found in 10 liver and/or spleen specimens of alabama 29-to-49-day-old commercial broiler chickens exhibiting lymphocyte depletion of the thymus submitted to the state diagnostic laboratory because of problems unrelated to anemia. we determined the nucleotide sequence directly from dna isolated from tissues, without i ...200111417817
detection of chicken anemia virus dna in the thymus of naturally infected chicks in turkey.in this study, 94 clinically ill 11-28-day-old chicks belonging to eight broiler units from the marmara region were investigated clinically for changes in hematocrit values and for the presence of chicken anemia virus (cav) dna. cav dna was detected by polymerase chain reaction in the thymus of 8.5% of the chicks. these chicks showed clinical signs of diarrhea, anorexia, depression, and growth retardation. the hematocrit values of these chicks were between 24% and 38%. at necropsy, hemorrhages w ...200111417840
[simultaneous expression of chicken anaemia virus proteins vp1 and vp2 in silkworms].by cloning vp1 and vp2 genes of chicken anaemia virus into transfer vector pbacpak8, recombinant transfer plasmids pbac-vp1 and pbac-vp2 were obtained. then bmn cells were co-transfected with linearized baculovirus bm-bacpak6 dna and above two recombinant plasmids respectively, recombinant viruses bm-vp1 and bm-vp2 were constructed and used to co-infect silkworms to express recombinant proteins. the results indicated that recombinant vp1 and vp2 could induce the corresponding antibody in chicken ...200111517601
epidemiology and significance of chicken infectious anemia virus infections in broilers and broiler parents under nonvaccinated european circumstances.a serologic survey in unvaccinated broiler parent and broiler progeny flocks demonstrated seroconversion against chicken infecrious anemia virus (ciav) in all parent flocks before or around point of lay and in 38% of the broiler flocks examined at slaughter age. the presence of ciav antibodies at slaughter of broilers was positively correlated with slaughterhouse condemnation rates. results indicate that ciav infections are highly prevalent in both broiler parent and broiler flocks and that ciav ...200111569748
response to apoptin of diploid fibroblasts from cancer-prone syndromes. 200111761249
chicken infectious anemia in mexico: virus identification and serology survey.three chicken infectious anemia (cia) virus strains were isolated from 10 different sick broiler and replacement chicken flocks with the mdcc-msb1 cell line. one-day-old specific-pathogen-free chicks were inoculated later, with the three original samples being positive in tissue culture; one induced signs and lesions, another only lesions typical for cia. one isolate was selected for further trials and showed resistance to chloroform and heat (75 c for 5 min) and passed through a 45-nm filter me ...200111785883
development of strain-specific real-time pcr and rt-pcr assays for quantitation of chicken anemia virus.chicken anemia virus (cav) is a ubiquitous pathogen of poultry. a cav specific taqman-based pcr and rt-pcr assay for real-time quantitation of viral load and relative quantitation of virus-specific transcript levels was developed. detection of viral dna copy number from infected mdcc-cu147 cells was determined by extrapolation from a cav plasmid-based standard curve. viral load increased proportionally with increasing cell number harvested, increasing from 4x10(2) copies in 250 cells with 38% vi ...200211849692
gene therapy with apoptin induces regression of xenografted human hepatomas.the chicken anemia virus-derived apoptin protein shows remarkable specificity; namely, it induces apoptosis in tumor cells, but not in normal diploid cells. we have exploited the apoptin gene for use in cancer gene therapy. here we demonstrate that adenovirus-mediated intratumoral transfer and expression of the apoptin gene results in regression or complete remission of human hepatomas grown as xenografts in immune-deficient mice, and significantly increases their survival long term. early after ...200211924525
ttv, a new human virus with single stranded circular dna genome.tt virus (ttv) was found in 1997 from a hepatitis patient without virus markers. however, the real impact of ttv on liver diseases remains uncertain to date. due to the lack of suitable cell systems to support the growth of ttv, the biology of ttv is still obscure. this review tries to summarise the current status of ttv on aspects other than the taxonomic diversity of ttv. ttv was the first human virus with a single stranded circular dna genome. ttv was considered to be a member of circoviridae ...200211987140
[identification of a protein interacting with apoptin from human leucocyte cdna library by using yeast two-hybrid screening].to screen the protein interacting with apoptin from human leucocyte cdna library by using yeast two-hybrid system, four clones interacting with apoptin were identified. one of them was homologous with nmi (n-myc interaction protein). cell co-immunoprecipitation showed that apoptin could bind to nmi in mammalian cells. apoptin mutants t1, t2 and t3 lacked the c-terminal 11 aa,33-46 aa and both,respectively. apoptin mutants t2 and t3 failed to interact with nmi, suggesting that its 33-46 aa was pi ...200212019454
chicken anemia virus and infectious bursal disease virus interfere with transcription of chicken ifn-alpha and ifn-gamma mrna.chicken anemia virus (cav) and infectious bursal disease virus (ibdv) are the two most important viruses that cause immunosuppression in commercial chickens. because inapparent, subclinical infections by these viruses cause immunosuppression, there is need for assessment of the immune status of chickens. interference with induction of transcription for chicken interferon-alpha (chifn-alpha) and chifn-gamma was noted after subclinical infections with either cav or ibdv. because the immunosuppress ...200212034026
molecular basis of the attenuation exhibited by molecularly cloned highly passaged chicken anemia virus isolates.chimeric virus experiments indicated that the pathogenicity and monoclonal antibody reactivity differences between two molecularly cloned, highly passaged chicken anemia virus isolates could be attributed to the vp1 amino acid change at residue 89. the introduction of this change into a pathogenic cloned low-passage isolate was not sufficient to cause attenuation.200212134051
chicken anemia virus vp2 is a novel dual specificity protein phosphatase.the function of viral protein 2 (vp2) of the immunosuppressive circovirus chicken anemia virus (cav) has not yet been established. we show that the cav vp2 amino acid sequence has some similarity to a number of eukaryotic, receptor, protein-tyrosine phosphatase (ptpase) alpha proteins as well as to a cluster of human tt viruses within the sanban group. to investigate if cav vp2 functions as a ptpase, purified glutathione s-transferase (gst)-vp2 fusion protein was assayed for ptpase activity usin ...200212151384
isolation, identification and characterization of chicken anaemia virus in malaysia.a study was conducted to isolate and identify chicken anaemia virus (cav) from field samples of clinically infected broiler chickens in malaysia. a total of 125 samples were collected from chickens aged 2-6 weeks with clinically depressed and retarded growth, of which five samples were found positive to cav directly by polymerase chain reaction (pcr). later, five isolates of cav from the respective five pcr positive samples were isolated in mdcc-msb1 cells at passage 4 based on cytopathic effect ...200212186740
development of a modified method for sequencing high g:c regions in chicken anemia virus genome.two areas in the chicken anemia virus (cav) genome have high g:c content with secondary structures. these two g:c rich areas could not be sequenced with perkin elmer's big dye terminator cycle sequencing kit. several modifications were carried out to solve the problem. finally, a package of modified method was developed to sequence the high g:c areas. the result showed that the perkin elmer's big dye terminator cycle sequencing kit with the normal procedures are not suitable for sequencing the h ...200212186760
prevention of inclusion body hepatitis/hydropericardium syndrome in progeny chickens by vaccination of breeders with fowl adenovirus and chicken anemia virus.the hypothesis that an effective protection of progeny chickens against inclusion body hepatitis/hydropericardium syndrome (ibh/hp) can be achieved by dual vaccination of breeders with fowl adenovirus (fav) serotype 4 and chicken anemia virus (cav) was tested. thus, 17-wk-old brown leghorn pullet groups were vaccinated by different schemes including single fav (inactivated), single cav (attenuated), fav and cav dually, or were not vaccinated (controls). subsequent progenies of these breeders wer ...200212243517
a tumor-specific kinase activity regulates the viral death protein apoptin.apoptin, a chicken anemia virus-encoded protein, is thought to be activated by a general tumor-specific pathway, because it induces apoptosis in a large number of human tumor or transformed cells but not in their normal, healthy counterparts. here, we show that apoptin is phosphorylated robustly both in vitro and in vivo in tumor cells but negligibly in normal cells, and we map the site to threonine 108. a gain-of-function point mutation (t108e) conferred upon apoptin the ability to accumulate i ...200212393903
sequence analysis of the full-length cloned dna of a chicken anaemia virus (cav) strain from bangladesh: evidence for genetic grouping of cav strains based on the deduced vp1 amino acid sequences.chicken anaemia virus (cav) was detected in the bursa of fabricius of a 4-week-old chicken obtained from an outbreak of acute infectious bursal disease in bangladesh. repeated attempts to grow this virus in mdcc-msb1 cells were not successful. a full-length pcr amplicon of the genome of this strain, designated as bd-3 cav, was cloned and sequenced. the complete nucleotide sequence and the deduced amino acid sequence were compared with those of 12 other cav strains. the genetic analysis of the am ...200212420868
comparison of a putative second serotype of chicken infectious anemia virus with a prototypical isolate i. pathogenesis.ciav-7 is a virus with similar pathogenic and physicochemical characteristics to, but antigenically distinct from, chicken infectious anemia virus (ciav). the pathogenesis of ciav-7 was evaluated in a comparative study with a representative isolate of ciav, the del-ros strain. the pathogenesis of ciav-7 was similar to del-ros on the basis of the clinical disease induced and gross and microscopic lesions, although ciav-7 produced fewer and less severe lesions overall. a second comparative pathoge ...200212495056
comparison of a putative second serotype of chicken infectious anemia virus with a prototypical isolate ii. antigenic and physicochemical characteristics.a putative new serotype of chicken infectious anemia virus (ciav) isolated from 17-wk-old broiler breeder pullets was compared with a known, previously characterized ciav isolate, the del-ros strain. physicochemical characteristics evaluated induded thermal stability, size, ph, and chloroform sensitivity. physicochemically, ciav-7 was identical to ciav. the virus isolates were compared antigenically by enzyme-linked immunosorbent assay, virus neutralization, immunofluorescence assay, and western ...200212495057
[gene cloning and sequencing of chicken anemia virus(cav) isolated from harbin].a chicken anemia virus has been isolated from a chicken flock in harbin of china. the genome of the ivrus was cloned through polymerase chain reaction(pcr) and sequence of the genome was analyzed. the cycle genome is made of 2298 base pairs including three overlapping open reading frames(vp1, vp2, vp3) and a regulative region. comparing sequence of the genome through blast in genbank, this sequence exhibits 96.9% identity with other genome of ca vs and least. multiple alignment of this genome of ...200212557549
detection of pigeon circovirus by polymerase chain reaction.pigeon circovirus was identified by polymerase chain reaction (pcr) in young pigeons belonging to 12 different lofts. viral dna was extracted from formalin-fed, paraffin-imbedded tissues containing primarily bursa and occasionally liver and spleen with a commercial kit. pcr primers were selected from a published sequence for columbid circovirus and evaluated in a pcr assay. the histopathologic examination of various tissues revealed basophilic globular intracytoplasmic inclusions in the mononucl ...200312713182
disseminated mycosis in layer cockerels and pullets.eight-wk-old layer cockerels and pullets were presented to the diagnostic lab with a history of increased mortality, ruffled feathers, lameness, and recent vaccination. at necropsy, the birds had large multifocal granulomas in multiple tissues. only light bacterial growth was seen on culture. on histopathology, a mixed population of fungi was seen within the granulomas including zygomycetes and aspergillus, with the zygomycetes being the predominant organism. because of the coinfection with aspe ...200312713184
the viral death protein apoptin interacts with hippi, the protein interactor of huntingtin-interacting protein 1.apoptin, a chicken anemia virus-encoded protein, induces apoptosis in human tumor cells but not in normal cells. the tumor-specific activity of apoptin is correlated with its nuclear localization in tumor cells. in an attempt to elucidate the molecular mechanism of apoptin-induced apoptosis, we identified human hippi, the protein interactor and apoptosis co-mediator of huntingtin interacting protein 1, as one of the apoptin-associated proteins by yeast two-hybrid screen. we also demonstrated tha ...200312745083
infection with chicken anaemia virus impairs the generation of pathogen-specific cytotoxic t lymphocytes.infection with chicken anaemia virus (cav), a circovirus, can result in immunosuppression and subsequent increased susceptibility to secondary infections. this is the first report of impairment of pathogen-specific cytotoxic t lymphocytes (ctl) after natural and experimental infection of chickens with cav and marek's disease virus (mdv) or reticuloendotheliosis virus (rev). mdv- and rev-specific ctl were generated at 7 days post infection by 9-30-day-old-chickens that were positive for maternal ...200312757624
immune responses against salmonella enterica serovar enteritidis infection in virally immunosuppressed chickens.to understand the role of immune mechanisms in protecting chickens from salmonella infections, we examined the immune responses of salmonella enterica serovar enteritidis-infected chickens and the effect of chicken anemia virus (cav), a t-cell-targeted virus, on s. enterica serovar enteritidis-induced immune responses. one-day-old chicks were orally inoculated with s. enterica serovar enteritidis with or without intramuscular injection of cav. the bacterial infection, pathology, and immune respo ...200312853403
apoptin protein multimers form distinct higher-order nucleoprotein complexes with dna.the chicken anaemia virus-derived protein apoptin is a tumour-specific cell-killing agent. it is biologically active as a highly stable, multimeric complex, consisting of 30-40 monomers. in tumour cells, but negligibly in normal cells, apoptin is imported into the nucleus prior to the induction of apoptosis. immunoelectron microscopic data we report here indicate that apoptin predominantly co-localises with heterochromatin and nucleoli within tumour cells. apoptin's preference for these dna-dens ...200312907722
recombinant apoptin multimers kill tumor cells but are nontoxic and epitope-shielded in a normal-cell-specific fashion.apoptin, a protein derived from chicken anemia virus, induces apoptosis in human transformed or tumor cells but not in normal cells. when produced in bacteria as a recombinant fusion with maltose-binding protein (mbp-apoptin), apoptin forms a distinct, stable multimeric complex that is remarkably homogeneous and uniform. here, using cytoplasmic microinjection, we showed that recombinant mbp-apoptin multimers retained the characteristics of the ectopically expressed wild-type apoptin; namely, the ...200312941602
experimental study on the antitumor effect of chicken anemia virus vp3 gene against liver carcinoma in vivo.in order to testify the antitumor effect, especially its effect against liver carcinoma in vivo, of vp3 protein, one kind of protein coded by chicken anemia virus, recombinants pcdna-vp3 containing chicken anemia virus vp3 gene, and control vector pcdna3 were mixed with murine liver carcinoma cell lines h22 respectively. the mixture was injected subcutaneously into balb/c mice. some days later, the mice were killed and the solid tumor weighed. the antitumor efficiency was evaluated. the manners ...200312973921
characterization of a spontaneously transformed chicken mononuclear cell line.we describe the characterization of a spontaneously transformed chicken monocytic cell line that developed as a single colony of cells in a heterophil culture that was inadvertently left in the incubator over a period of 25 days. these cells, hitherto named htc, grow efficiently at both 37 or 41 degrees c in culture medium containing either 5% fbs or 2% chicken serum. the htc cells are acid phosphatase positive, show expressions of both class i and class ii major histocompatibility complex (mhc) ...200314522138
monoclonal antibody technology: applications in veterinary science.monoclonal antibodies have revolutionised the study of animals and their diseases. the author looks at the detection of antigen in samples using a range of techniques from indirect fluorescence, through in-situ hybridization to enzyme linked immunosorbent assays. examples are given of how salmonella species, mastitis antigens, viral antigens, chlamydial organisms and e. coli toxins can be detected using specific monoclonal antibodies. the recognition of antigen in tissues by monoclonal antibodie ...199414545927
detection of chicken anemia virus dna in embryonal tissues and eggshell membranes.chicken infectious anemia virus (ciav) is a ubiquitous and highly resistant virus of chickens that causes anemia and death in chicks less than 3 wk of age and immunosuppression in chickens older than 3 wk of age. the production of specific-pathogen-free eggs free of ciav is essential for research and vaccine production. currently, flocks are screened for ciav by antibody tests to ensure freedom from ciav infection. recent evidence, however, indicates that chickens may carry and vertically transm ...200314562895
comparison of the structures of three circoviruses: chicken anemia virus, porcine circovirus type 2, and beak and feather disease virus.circoviruses are small, nonenveloped icosahedral animal viruses characterized by circular single-stranded dna genomes. their genomes are the smallest possessed by animal viruses. infections with circoviruses, which can lead to economically important diseases, frequently result in virus-induced damage to lymphoid tissue and immunosuppression. within the family circoviridae, different genera are distinguished by differences in genomic organization. thus, chicken anemia virus is in the genus gyrovi ...200314645560
bag-1 inhibits p53-induced but not apoptin-induced apoptosis.bag-1 has been identified as a bcl-2-binding protein that inhibits apoptosis, either alone or in co-operation with bcl-2. here we show that bag-1 inhibits p53- induced apoptosis in the human tumour cell line saos-2. in contrast, bag-1 was unable to inhibit the p53-independent pathway induced by apoptin, an apoptosis-inducing protein derived from chicken anaemia virus. whereas bag-1 seemed to co-operate with bcl-2 to repress p53-induced apoptosis, co-expression of these proteins had no inhibitory ...199714646536
pathogenicity, sequence and phylogenetic analysis of malaysian chicken anaemia virus obtained after low and high passages in msb-1 cells.specific-pathogen-free (spf) chickens inoculated with low passage chicken anaemia virus (cav), smsc-1 and 3-1 isolates produced lesions suggestive of cav infection. repeated passages of the isolates in cell culture until passage 60 (p60) and passage 123 produced viruses that showed a significantly reduced level of pathogenicity in spf chickens compared to the low passage isolates. sequence comparison indicated that nucleotide changes in only the coding region of the p60 passage isolates were tho ...200314648297
real-time quantitative pcr-based serum neutralization test for detection and titration of neutralizing antibodies to chicken anemia virus.detection and titration of chicken anemia virus (cav)-neutralizing antibodies has relied on tedious, time-consuming passaging of infected cells, or subjective recognition of cytopathic effect in individual cells, because cav replicates in culture only in lymphoblastoid cell lines, and thus generates no plaques. this paper describes a rapid method, in which cav genomes in infected cells are quantitated by qpcr 3-4 days postinfection (p.i.), without passaging cells. three sera, weakly positive wit ...200414667528
chicken anemia virus in broilers: dynamics of the infection in two commercial broiler flocks.chicken anemia virus (cav) can cause a disease syndrome characterized by severe anemia, bone marrow atrophy, and severe immunosuppression in young chicks. maternal antibodies prevent these clinical signs but do not prevent infection, transmission of the virus, or immunosuppression. the clinical disease is rare today because of the widespread practice of vaccinating breeders, but the subclinical form of the disease is ubiquitous. the dynamics of cav infection, cav antibody responses, relative lym ...200314708998
avian circovirus diseases: lessons for the study of pmws.the diseases associated with psittacine beak and feather disease virus (bfdv), pigeon circovirus (picv) and goose circovirus (gocv), which can be classified with porcine circovirus type 2 (pcv2) as members of the genus circovirus of the family circoviridae, have clinico-pathological features in common with post-weaning multisystemic wasting syndrome (pmws), with which pcv2 infection is causally associated. intracytoplasmic botryoid inclusions within macrophages and depletion of t and b lymphocyt ...200414741130
human death effector domain-associated factor interacts with the viral apoptosis agonist apoptin and exerts tumor-preferential cell killing.apoptin, a protein from chicken anemia virus without an apparent cellular homologue, can induce apoptosis in mammalian cells. its cytotoxicity is limited to transformed or tumor cells, making apoptin a highly interesting candidate for cancer therapy. to elucidate apoptin's mechanism of action, we have searched for binding partners in the human proteome. here, we report that apoptin interacts with dedaf, a protein previously found to associate with death effector domain (ded)-containing pro-apopt ...200414765135
cloning of chicken anemia virus vp3 gene and apoptosis inductive effect of vp3 gene in vitro.using pcr technique, the vp3 gene of chicken anemia virus (cav) was cloned into the eukaryotic expression vector pcdna3 to construct a recombinant pcdna-vp3. restriction enzyme digestion and sequencing analysis revealed that cav vp3 gene was correctly inserted into the blank vector pcdna3. after lipofectamine-mediated transfection in vitro with pcdna-vp3 and pcdna3 respectively, the total mrna was extracted from liver carcinoma cell lines hepg2 and diploid cell line l-02, and rt-pcr was performe ...200315015627
serologic evidence of chicken infectious anemia in commercial chicken flocks in southwest nigeria.sera samples from seven poultry farms in southwest nigeria consisting of 7 broiler, 10 pullet, 1 layer, 1 cockerel, and 1 broiler breeder flocks were tested for the presence of chicken infectious anemia virus (ciav) antibodies using a commercial enzyme-linked immunosorbent assay kit. eleven of the 20 flocks (55%) and six out of seven (86%) farms were positive for ciav antibodies. the seroprevalence largely depended on the age of the flocks. seroprevalence was higher within the older pullet and l ...200415077816
a serological survey for pathogens in old fancy chicken breeds in central and eastern part of the netherlands.to get an impression of the presence of pathogens in multi-aged flocks of old fancy chicken breeds in the netherlands, plasma samples originating from 24 flocks were examined for antibodies against 17 chicken pathogens. these flocks were housed mainly in the centre and east of the netherlands, regions with a high poultry density. the owners of the tested flocks showed their chicken at national and international poultry exhibitions. antibodies against avian influenza, egg drop syndrome '76 virus, ...200415185615
development of a multiplex pcr for detection of avian adenovirus, avian reovirus, infectious bursal disease virus, and chicken anemia virus.a multiplex polymerase chain reaction (mpcr) was developed and optimized for the simultaneous detection and differentiation of avian reovirus (arv), avian adenovirus group i (aav-i), infectious bursal disease virus (ibdv), and chicken anemia virus (cav). four sets of specific oligonucleotide primers were used in this test for arv, aav-i, ibdv, and cav. the mpcr dna products were visualized by gel electrophoresis and consisted of fragments of 365 bp for ibdv, 421 bp for aav-i, 532 bp for arv, and ...200415294316
the viral protein apoptin associates with the anaphase-promoting complex to induce g2/m arrest and apoptosis in the absence of p53.the chicken anemia virus protein apoptin induces apoptosis in the absence of p53 by a mechanism that remains to be elucidated. here we show that in transformed cells, apoptin is associated with apc1, a subunit of the anaphase-promoting complex/cyclosome (apc/c). we demonstrate that apoptin expression, or depletion of apc1 by rna interference, inhibits apc/c function in p53 null cells, resulting in g2/m arrest and apoptosis. our results explain the ability of apoptin to induce apoptosis in the ab ...200415314021
activation of the tumor-specific death effector apoptin and its kinase by an n-terminal determinant of simian virus 40 large t antigen.apoptin, a viral death protein derived from chicken anemia virus, displays a number of tumor-specific behaviors. in particular, apoptin is phosphorylated, translocates to the nucleus, and induces apoptosis specifically in tumor or transformed cells, whereas it is nonphosphorylated and remains primarily inactive in the cytoplasm of nontransformed normal cells. here, we show that in normal cells apoptin can also be activated by the transient transforming signals conferred by ectopically expressed ...200415331730
genetic diversity of chicken anemia virus following cell culture passaging in msb-1 cells.it has been shown that a chicken anemia virus (cav) isolates which had undergone 60 passages in msb-1 cells (smsc-1/p60, 3-1/p60) acquired 33-66 nucleotide substitutions at the coding region resulting in 13-16 amino acid changes as compared to the cav isolates passaged only 5 times in msb-1 cells (smsc-1 and 3-1) (chowdhury et al., arch. virol. 148, 2437-2448, 2003). in this study we found that a low cav (bl-5) and a high cav passage (bl-5/p90) differed by only 15 nucleotide substitutions result ...200415462283
pathogenesis of chicken anemia virus: comparison of the oral and the intramuscular routes of infection.the events during the pathogenesis of chicken anemia virus (cav) infection following intramuscular (im) and oral inoculation were further elucidated and compared by sequential clinical, pathologic, and morphometric histopathologic evaluations, and by sequential determination of cav genome concentrations in different organs. specific-pathogen-free chickens were inoculated by im or oral routes with the same dose (2 x 10(6) mean tissue culture infective dose [tcid50]) of cav isolate 03-4876 at 1 da ...200415529971
a putative nes mediates cytoplasmic localization of apoptin in normal cells.apoptin, a protein expressed by chicken anemia virus, is found predominantly in the cytoplasm in normal cells, whereas it localizes in the nucleus in transformed and malignant cells. however, the mechanisms that regulate the different subcellular localization of apoptin in normal and tumor cells have not been fully clarified. in this work, a putative nuclear export signal (nes) in apoptin was predicted. it was testified that the putative nes (pnes) of apoptin was not a functional nes, but actual ...200415592649
a tumor cell-specific nuclear targeting signal within chicken anemia virus vp3/apoptin. 200515613363
enhanced expression of apoptin by the myc-max binding motif and sv40 enhancer for sclc gene therapy.apoptin is derived from chicken anemia virus (cav) and known to induce tumor specific apoptosis but not normal cells. the aim of this study was to use increased expression of apoptin by the myc-max response element (mmre) and sv40 enhancer in small-cell lung cancer (sclc) gene therapy. to investigate the possibility of the utilization of the mmre, apoptin, and sv40 promoter/enhancer in targeted cancer gene therapy, adenovirus vector expressing apoptin controlled by the mmre, and sv40 promoter/en ...200515665467
[molecular mechanism of specific induction of apoptosis in tumor cells by apoptin].apoptin, a small protein derived from chicken anemia virus, can specifically induce apoptosis in transformed cells or tumor cells, but not in normal cells. the tumor specificity of apoptin relates to its subcellular localization. in transformed cells or tumor cells, apoptin migrates to the nuclei, whereas in non-transformed cells, it remains mainly within the cytoplasm. phosphorylation is responsible for the nuclear localization of apoptin. in tumor cells, apoptin is phosphorylated, then translo ...200515820081
role of viral load in the pathogenesis of chicken anemia virus.the pathogenesis of strain 3711 of the chicken anemia virus (cav), propagated in chickens, and two preparations of strain 3711 that had been adapted to grow to high titre in cells of the mdcc-msb1 line were studied in chicken embryos and/or chickens. highest viral loads in infected chickens, as measured by a microplate dna-hybridization assay, were detected in the thymus, clotted blood and pancreas, and the lowest in the duodenum. the cav dna copy number in the organs of chicken embryos was sign ...200515831943
pigeon paramyxovirus: association with common avian pathogens in chickens and serologic survey in wild birds.pigeon paramyxovirus-1 (ppmv-1) was isolated from pigeons from east-central alabama and used in association with chicken anemia virus (cav), infectious bursal disease virus (ibdv), or finch mycoplasma gallisepticum (mg) in specific-pathogen-free chickens to assess dinical disease and pathology. ppmv-1 infection in all groups was conducted at day 10 of age via the ocular route. the low passage ppmv-1 isolate was inoculated into chickens in different groups at 10 days post-cav infection, 6 days po ...200515839419
the anaphase promoting complex: a critical target for viral proteins and anti-cancer drugs.the study of animal viruses has provided extraordinary insights into cell cycle dynamics and tumor biology. the significance of the p53 and rb tumor suppressor proteins, for example, was discovered due to their interactions with viral oncogenes. in the past several years, investigations with four viral proteins, human immunodeficiency virus type 1 (hiv-1) vpr, adenovirus e4orf4, chicken anemia virus (cav) apoptin and human t lymphotropic virus type i (htlv-i) tax, have indicated that there are a ...200515876865
apoptin induces chromatin condensation in normal cells.apoptin, a chicken anemia virus protein, was reported to induce tumor specific apoptosis, which was correlated with the nuclear localization of the protein in tumor cells. while in normal human cells, apoptin was detected mainly in the cytoplasm and did not induce apoptosis. using a recombinant adenovirus expressing apoptin, we have found that apoptin induced g(2)-m cell cycle arrest and chromatin condensation in cancer cells. here we report that adenovirus mediated apoptin expression also induc ...200515965608
serological evidence of chicken anaemia virus infection in nigerian indigenous chickens.serum samples from 20 out of 180 (11.1%) apparently healthy nigerian indigenous chickens were negative for antibodies against chicken anaemia virus using the enzyme-linked immunosorbent assay (elisa). of the 160 positive sera (88.9%), 12 (7.5%) had titres ranging from 1500-3000, 46 (28.8%) had titres from 3000-5000 while 102 (63.8%) had titres between 5000-11000. the overall mean titre value was 5845 +/- 2402. this appears to be evidence of a natural outbreak of the infection since the chickens ...200515991709
isolation of chicken anaemia virus from broiler chickens in new zealand.chicken anaemia virus was isolated for the first time in new zealand from the new zealand domestic chicken population. the virus was recovered from diseased birds in five separate flocks of broiler chickens aged between 14 and 33 days of age. six isolates were obtained from bone marrow and lymphoid tissues using the mdcc-msb1 cell line derived from marek's disease lymphoma. all isolates were resistant to chloroform and survived exposure to 70 degrees c for 5 minutes. the main clinical features c ...199416031747
molecular epidemiology of chicken anemia virus in nigeria.between february 2002 and may 2004, chicken anemia virus (cav) was detected by pcr in organ samples from 14 flocks of poultry farms in lagos, ogun and oyo states in southwestern nigeria. the farms reported low (<5%) to high mortalities (up to 100%) with various lesions at necropsy. the complete vp1 gene of 30 of these positive strains was sequenced. strains that diverged by up to 4.4% on a nucleotide level differed only by up to 2.5% at the amino acid level (7 aa) as a result of clustered silent ...200616096706
apoptin acts as a tumor-specific killer: potentials for an anti-tumor therapy.apoptin, a protein encoded by an avian virus, induces apoptosis in a tumor-specific way, acts p53-independently and is even stimulated by the anti-apoptotic protein bcl-2. activation of upstream caspases is not required, whereas the activation of downstream caspases is involved in rapid apoptin-induced cell death. yet, in a caspase-3-negative human breast cancer cell line, apoptin can induce apoptosis, but delayed. these features indicate that apoptin can induce apoptosis via multiple pathways i ...200516171564
cancer-specific toxicity of apoptin is independent of death receptors but involves the loss of mitochondrial membrane potential and the release of mitochondrial cell-death mediators by a nur77-dependent pathway.apoptin, a small proline-rich protein derived from the chicken anaemia virus, induces cell death selectively in cancer cells. the signalling pathways of apoptin-induced, cancer cell-selective apoptosis are not well understood. here, we demonstrate that apoptin triggers apoptosis by activating the mitochondrial/intrinsic pathway, and that it acts independently of the death receptor/extrinsic pathway. jurkat cells deficient in either fadd or caspase-8 (which are both necessary for the extrinsic pa ...200516179607
isolation and preliminary characterization of chicken anemia virus from chickens in nigeria.chicken anemia virus (cav) was isolated for the first time from the nigerian chicken population. the virus was recovered from necropsied birds from broiler and pullet flocks that suffered disease outbreaks tentatively diagnosed as infectious bursal disease. a sensitive polymerase chain reaction (pcr) assay detected cav dna in tissues of necropsied birds. restriction endonuclease analysis performed with the 733-bp pcr product and the cfo i enzyme indicated at least two different cavs were circula ...200516252505
apoptin-induced cell death is modulated by bcl-2 family members and is apaf-1 dependent.apoptin, a chicken anemia virus-derived protein, selectively induces apoptosis in transformed but not in normal cells, thus making it a promising candidate as a novel anticancer therapeutic. the mechanism of apoptin-induced apoptosis is largely unknown. here, we report that contrary to previous assumptions, bcl-2 and bcl-xl inhibit apoptin-induced cell death in several tumor cell lines. in contrast, deficiency of bax conferred resistance, whereas bax expression sensitized cells to apoptin-induce ...200616288204
biological and molecular characterization of chicken anaemia virus isolates of indian origin.in the present study, four chicken anaemia virus (cav) isolates (cav-a, -b, -e and -p) recovered from different geographical regions of india were characterized. cav genome of 1,766 bp nucleotide region containing the complete coding region of vp2 and vp3 proteins, and partial coding region of vp1 protein were sequenced. the nucleotide and deduced amino acid sequence of the indian cav isolates were aligned and compared with cav isolates of european, asian, american and australian origin. phyloge ...200616384622
oral infection with chicken anemia virus in 4-wk broiler breeders: lack of effect of major histocompatibility b complex genotype.the pathologic consequences of chicken anemia virus (cav) oral inoculation in 4-wk-old broiler breeders of different major histocompatibility b complex (mhc) genotypes were evaluated. mhc b complex was determined by hemagglutination and sequence-based typing. clinical signs, serology, gross lesions, histopathologic analysis, and cav genome quantification were used to evaluate disease progression. clinical disease was not apparent in the inoculated broilers throughout the experimental period. at ...200516404987
tumor-specific nuclear targeting: promises for anti-cancer therapy?recent developments in anti-cancer gene therapy suggest that the idea of a magic bullet for cancer may not be a pipe dream. viral-based anti-cancer vectors for gene therapy have been used preferentially in this regard, but recent results from clinical trials have raised serious concerns as to their safety. for this reason, the development of non-viral vectors able to deliver drugs or suicide genes specifically to cancer cells is of paramount importance. in this context, great interest has been r ...200616621677
chicken anaemia virus inoculated by the oral route causes lymphocyte depletion in the thymus in 3-week-old and 6-week-old chickens.there have been many reports of the severe clinical disease and pathology seen in young chicks that have been vertically infected with chicken anaemia virus (cav). the disease is characterized by anaemia, and atrophy of the thymus and bone marrow. however, while it has been suggested that horizontally acquired infections of older birds are common, to date there has been no description in the literature of the pathology of this type of infection. in the present study, 3-week-old and 6-week-old ch ...200616753618
fibroblast-like synoviocytes from patients with rheumatoid arthritis are more sensitive to apoptosis induced by the viral protein, apoptin, than fibroblast-like synoviocytes from trauma patients.fibroblast-like synoviocytes (fls) from patients with rheumatoid arthritis (ra) show characteristics of transformation. because the chicken anemia virus protein, apoptin, induces apoptosis solely in transformed cells, it was investigated whether fls from patients were more sensitive to apoptin-induced apoptosis than fls from normal joints obtained from trauma patients.200616762148
induction of an effective anti-tumor immune response and tumor regression by combined administration of il-18 and apoptin.immunization strategies using plasmid dna can potentially improve humoral and cellular immune responses that protect against cancer and infectious diseases. the chicken anemia virus-derived apoptin protein exhibits remarkable specificity in its ability to induce apoptosis in tumor cells, but not in normal diploid cells. interleukin-18 (il-18) is a th1-type cytokine that has demonstrated potential as a biological adjuvant in murine tumor models. in this study, we analyzed the anti-tumor potential ...200716767432
characterization and phylogenetic analysis of brazilian chicken anaemia virus.chicken anaemia virus (cav) was detected by a nested-pcr assay in field samples from different regions of brazil. the 539 bp amplified fragments of vp1 gene from 44 field samples were sequenced and 10 new nucleotide sequences of cav were observed. these sequences were phylogenetically analysed by mega2 using neighbour joining distance methods with 1000 bootstrap replications. phylogenetic analysis did not show correlation between cav pathology pattern and genetic groups. the 10 nucleotide sequen ...200616791412
apoptin nucleocytoplasmic shuttling is required for cell type-specific localization, apoptosis, and recruitment of the anaphase-promoting complex/cyclosome to pml bodies.the chicken anemia virus protein apoptin selectively induces apoptosis in transformed cells while leaving normal cells intact. this selectivity is thought to be largely due to cell type-specific localization: apoptin is cytoplasmic in primary cells and nuclear in transformed cells. the basis of apoptin cell type-specific localization and activity remains to be determined. here we show that apoptin is a nucleocytoplasmic shuttling protein whose localization is mediated by an n-terminal nuclear ex ...200616840333
immunopathogenesis of attenuated strain of chicken infectious anemia virus in one-day-old specific-pathogen-free chicks.in the present study, the immunopathogenicity of chicken anemia virus (cav) vaccinal strain was studied in one-day-old specific-pathogen-free (spf) chicks. hematocrit values, histopathological changes in haemopioetic and lymphoid organs, elisa for cav antibodies and pcr for cav genome were used as testing assays for the study. vaccinated chicks showed signs of anemia, lower hematocrit values and histopathological lesions in liver in the form of hepatocytes swelling to centro lobular necrosis and ...200315726722
the anti-nuclease humoral immune response of broiler chickens exposed to staphylococcus aureus, infectious bursal disease virus and chicken anaemia virus in an experimental model for bacterial chondronecrosis and osteomyelitis.this study aimed to develop an enzyme-linked immunosorbent assay to detect antibody associated with staphylococcus aureus that is produced during the chicken immune response to this organism. the protein nuclease was tested for suitability as an antigen to detect antibody in sera from broiler chickens that had been exposed to aerosolized s. aureus on day 1 post hatch during experiments to reproduce bacterial chondronecrosis and osteomyelitis. an enzyme-linked immunosorbent assay was developed to ...200616854643
positive and negative regulation of chicken anemia virus transcription.chicken anemia virus (cav) is a small circular single-stranded dna virus with a single promoter-enhancer region containing four consensus cyclic amp response element sequences (agctca), which are similar to the estrogen response element (ere) consensus half-sites (a)ggtca. these sequences are arranged as direct repeats, an arrangement that can be recognized by members of the nuclear receptor superfamily. transient-transfection assays which use a short cav promoter construct that ended at the tra ...200515709005
chicken infectious anemia virus: an example of the ultimate host-parasite relationship.chicken infectious anemia virus (ciav) is a resistant and ubiquitous virus of chickens causing disease in young chickens and immunosuppression in all birds. this paper reviews the current knowledge of ciav with a focus on new findings indicating that immunosuppressive effects have not been fully appreciated, especially as they relate to the development of antigen-specific cytotoxic t cells. a more complete understanding of the immunosuppressive effects of ciav emphasizes the need for better vacc ...200415666854
anti-neoplastic effect of chicken anemia virus vp3 protein (apoptin) in rous sarcoma virus-induced tumours in chicken.the anti-neoplastic effect of chicken anemia virus vp3 protein (apoptin) was investigated in vitro in rous sarcoma virus (rsv)-transformed chicken embryo fibroblast (cef) cells and in rsv-induced tumours of specific-pathogen-free (spf) chicks in vivo. the apoptin gene was cloned in the pvax expression vector and in vitro expression of the recombinant vector pvax-cav-vp3 was confirmed. two groups of spf chicks, each containing ten chicks, were used. chicks in groups i and ii were inoculated with ...200616963752
detection of chicken anemia virus in the gonads and in the progeny of broiler breeder hens with high neutralizing antibody titers.previous evidence for the presence of chicken anemia virus (cav) in the gonads of immune specific-pathogen-free chickens raised the question whether this occurs also in commercial breeders. the presence of cav was investigated by nested pcr in the gonads and spleens of hens from two 55- and 59-week-old, cav-vaccinated (flocks 2 and 3), and two 48- and 31-week-old non-vaccinated broiler breeder flocks (flocks 1 and 4). in addition, lymphoid tissues of 20-day-old embryos from these hens were also ...200415607085
[killing effect of vp3 on human nasopharyngeal carcinoma cell line cne-2 cells].to investigate the killing effects of vp(3) on nasopharyngeal carcinoma cell line cne-2.200617062935
resistance of porcine circovirus and chicken anemia virus to virus inactivation procedures used for blood products.virus inactivation procedures are used to prevent contamination of plasma-derived blood products with viruses. pasteurization or prolonged dry heat has proven effective against several enveloped and nonenveloped viruses and provides an additional layer of safety for plasma products.200617076851
epidemiological and experimental evidence for immunodeficiency affecting avian infectious bronchitis.we evaluated the effects of viral immunodeficiency on the outcome of infectious bronchitis virus (ibv) infection in chickens as a hypothetical cause for failure of adequate protection in vaccinated chickens. initially, we investigated ibv isolations from cases of respiratory disease in association with the presence of thymic and/or bursal atrophy in 322 submissions during 1997 to 2002. arkansas (ark)-type ibv was most frequently isolated in spite of extensive arkdpi vaccination in the broiler in ...200617121734
the viral death effector apoptin reveals tumor-specific processes.several natural proteins, including the cellular protein trail and the viral proteins e4orf4 and apoptin, have been found to exert a tumor-preferential apoptotic activity. these molecules are potential anti-cancer agents with direct clinical applications. also very intriguing is their possible utility as sensors of the tumorigenic phenotype. here, we focus on apoptin, discussing recent research that has greatly increased our understanding of its tumor-specific processes. apoptin, which kills tum ...200415258463
torque teno virus (ttv): current status.torque teno virus (ttv), currently classified into the family circoviridae, genus anellovirus, was first found in a patient with non-a-e hepatitis. ttv has a single stranded circular dna of approximately 3.8 kb. ttvs are extraordinarily diverse, spanning five groups including sanban and sen viruses. torque teno mini virus (ttmv) with approximately 2.9 kb genome also has wide variants. recently, two related 2.2- and 2.6-kb species joined this community. recombinations between variants are frequen ...200717146841
apoptin studies illuminate intersection between lipidomics and tumor suppressors. 200717164768
[expression of the vp2 gene of chicken infectious anemia virus in e. coli and analysis of immunogenicity].the coding region of vp2 gene from chicken infectious anemia was amplified from genome extracted from chicken liver tissue by pcr. pcr product was double digested with restriction enzymes bamh i and sal i and cloned into pet-28a digested with bamh i and sal i. subsequently, the recombinant plasmid pet-28-vp2 was extracted and double digested with restriction enzymes bamh i and sal i. after confirming its rightness by pcr and analysis of restriction endonucleases, the recombinant plasmid pet-28-v ...200617172042
genome sequencing analysis of brazilian chicken anemia virus isolates that lack msb-1 cell culture tropism.specific amino acid (aa) substitutions in vp1, vp2 and vp3 genes were reported as a distinctive feature of the american cia-1 strain, characterized as having a variable rate of growth and tropism for different msb-1 cell sublines [renshaw rw, soiné c, weinkle t, o'connell ph, ohashi k, watson s, et al. a hypervariable region in vp1 of chicken anemia virus mediates rate of spread and cell tropism in tissue culture. j virol 1996;70(12):8872-8]. dna sequencing of 878 nucleotides from twelve brazili ...200717196655
tt virus-derived apoptosis-inducing protein induces apoptosis preferentially in hepatocellular carcinoma-derived cells.tt virus (ttv) is widespread among the global population. its pathogenic nature is still unclear but ttv seems to be more prevalent in cases of hepatitis than in healthy individuals. ttv harbours similarities to chicken anaemia virus (cav). here, the apoptotic potential of a putative ttv-derived 105 aa protein and of the main apoptosis-inducing agent of cav, apoptin, is compared. as the putative protein induced apoptosis in various human hepatocellular carcinoma (hcc) cell lines, it was named tt ...200415166427
cloning and expression of chicken anemia virus vp3 protein in escherichia coli.purification of chicken anemia virus (cav) vp3 protein, expressed in a prokaryotic expression system as histidine-tagged fusion protein is demonstrated in the present study. cav particle was obtained from infected liver of chicken and dna was extracted. the vp3 protein gene was amplified from the extracted dna by polymerase chain reaction (pcr) and cloned. the recombinant expression construct (ptrc-vp3) was identified by pcr and sequencing analysis. expression of vp3 protein with a molecular mas ...200717258317
a modified blocking elisa for the detection of antibody to chicken anaemia virus using an australian strain. 200315084059
effect of the vp3 gene of chicken anemia virus on canine mammary tumor cells.to investigate the antitumor effect of the chicken anemia virus (cav) vp3 gene in canine mammary tumor (cmt) cells. sample populations: established primary canine cell lines that originated from epithelial cells of resected cmts and nonneoplastic mammary gland epithelial (mge) cells.200717397298
biological characteristics of chicken anemia virus regenerated from clinical specimen by pcr.our previous genetic characterization of chicken anemia virus (cav) in commercial broiler chickens in alabama revealed a previously undetected polymorphism: a glutamine codon at vp1 position 22, in 7 of the 14 sequences. the novel glutamine codon was always found in association with a vp1 "hypervariable region" identical to cav field isolates that replicate poorly in culture. the complete genome of cav73, representative of the sequences with the novel polymorphism, was generated from cloned poly ...200717461269
mapping of epitopes of vp2 protein of chicken anemia virus using monoclonal antibodies.to map the epitopes of vp2 protein of chicken anemia virus (cav), vp2 was expressed as a fusion protein in escherichia coli bl21 (de3). the western blot demonstrated that recombinant vp2 protein could be recognized by sera of chickens infected with cav. female balb/c mice were immunized with purified recombinant vp2 produced in e. coli bl21 (de3) and seven vp2-specific monoclonal antibodies (mabs) were developed. the results of western blot showed that all the seven mabs recognized the recombina ...200717481740
chicken infectious anemia virus infection in israeli commercial flocks: virus amplification, clinical signs, performance, and antibody status.the impact of chicken infectious anemia virus (ciav) infection on commercial chicken flocks in israel was examined by analyzing flocks with or without typical ciav signs, signs of other diseases, or apparently healthy flocks. in 23 flocks (broilers and layers) of ages up to 8 wk, typical signs of ciav infection (stunting, gangrenous dermatitis, and secondary bacterial infections) were recorded. when permitted by flock owners, in several cases among these 23 flocks the morbidity, mortality, and p ...200415077804
identification of chicken anemia virus putative intergenotype recombinants.chicken anemia virus (cav), the only member of the genus gyrovirus in the family circoviridae is the pathogen of chicken infectious anemia. it is unknown whether homologous recombination happens between cav strains. in order to gain insight into this matter, we have performed a phylogenetic analysis of full-length cav strains isolated to detect possible recombination events. two putative recombinants, sd24, sd22 and the putative parental-like strains were identified with the use of simplot progr ...200717618666
the tumour specific pro-apoptotic factor apoptin (vp3) from chicken anaemia virus.cancer is a growing problem for human health world-wide. dramatic breakthroughs have increased our understanding of the molecular mechanisms involved in the process of tumorigenesis, allowing us to develop more refined anti-cancer treatments, expanding the repertoire of available anti-cancer drugs, and increasing the efficiency of their delivery to malignant cells. nevertheless, even with improved understanding of the complex origins of cancer cells, there is a dearth of efficient and above all ...200415011951
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