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1.
BMC Cancer ; 22(1): 936, 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36038818

RESUMO

BACKGROUND: Melanoma is a malignant tumor characterized by high proliferation and aggressive metastasis. To address the molecular mechanisms of the proto-oncogene, Rous sarcoma oncogene (Src), which is highly activated and promotes cell proliferation, migration, adhesion, and metastasis in melanoma. Plectin, a cytoskeletal protein, has recently been identified as a Src-binding protein that regulates Src activity in osteoclasts. Plectin is a candidate biomarker of certain tumors because of its high expression and the target of anti-tumor reagents such as ruthenium pyridinecarbothioamide. The molecular mechanisms by which plectin affects melanoma is still unclear. In this study, we examined the role of plectin in melanoma tumor formation. METHODS: We used CRISPR/Cas9 gene editing to knock-out plectin in B16 mouse melanoma cells. Protein levels of plectin and Src activity were examined by western blotting analysis. In vivo tumor formation was assessed by subcutaneous injection of B16 cells into nude mice and histological analysis performed after 2 weeks by Hematoxylin-Eosin (H&E) staining. Cell proliferation was evaluated by direct cell count, cell counting kit-8 assays, cyclin D1 mRNA expression and Ki-67 immunostaining. Cell aggregation and adhesion were examined by spheroid formation, dispase-based dissociation assay and cell adhesion assays. RESULTS: In in vivo tumor formation assays, depletion of plectin resulted in low-density tumors with large intercellular spaces. In vitro experiments revealed that plectin-deficient B16 cells exhibit reduced cell proliferation and reduced cell-to-cell adhesion. Since Src activity is reduced in plectin-deficient melanomas, we examined the relationship between plectin and Src signaling. Src overexpression in plectin knockout B16 cells rescued cell proliferation and improved cell-to-cell adhesion and cell to extracellular matrix adhesion. CONCLUSION: These results suggest that plectin plays critical roles in tumor formation by promoting cell proliferation and cell-to-cell adhesion through Src signaling activity in melanoma cells.


Assuntos
Melanoma Experimental , Sarcoma Aviário , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Melanoma Experimental/metabolismo , Camundongos , Camundongos Nus , Oncogenes , Plectina/genética , Sarcoma Aviário/genética
2.
Genes Immun ; 23(1): 12-22, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34934184

RESUMO

Innate immune genes play an important role in the immune responses to Rous sarcoma virus (RSV)-induced tumor formation and metastasis. Here, we determined in vivo expression of chemokines, innate immune and apoptotic genes in Synthetic Broiler Dam Line (SDL) chickens following RSV-A infection. The mRNA expression of genes was determined at the primary site of infection and in different organs of progressor, regressor and non-responder chicks, using RT-qPCR. Our results indicated a significant upregulation of: (1) chemokines, such as MIP1ß and RANTES, (2) the innate immune gene TLR4, and (3) p53, a tumor-suppressor gene, at the site of primary infection in progressor chickens. In contrast, inducible nitric oxide synthase (iNOS) gene expression was significantly downregulated in progressor chicks compared to uninfected, control chicks. All of the innate immune genes were significantly upregulated in the lungs and liver of the progressor and regressor chicks compared to control chicks. In the spleen of progressor chicks, RANTES, iNOS and p53 gene expression were significantly increased, whereas MIP1ß and TLR4 gene expression was significantly downregulated, compared to control chicks. The lungs and livers of non-responder chicks expressed a low level of iNOS and MIP1ß, whereas RANTES, TLR4, and p53 gene expression were significantly upregulated compared to uninfected control chicks. In addition, there was a significant downregulation of RANTES, MIP1ß, and TLR4 gene expression in non-responder chicks. These results suggest the different response to infection of chicks with RSV-A is due to differential changes in the expression of innate immune genes in different organs.


Assuntos
Vírus do Sarcoma de Rous , Sarcoma Aviário , Animais , Quimiocina CCL5 , Galinhas/genética , Imunidade Inata/genética , Sarcoma Aviário/genética , Sarcoma Aviário/patologia , Receptor 4 Toll-Like , Proteína Supressora de Tumor p53/genética
3.
Poult Sci ; 100(9): 101335, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34329985

RESUMO

New arrangements of chicken major histocompatibility complex (MHC) class I BF and class IV BG genes are created through recombination. Characterizing the immune responses of such recombinants reveals genes or gene regions that contribute to immunity. Inbred Line UCD 003 (B17B17) served as the genetic background for congenic lines, each containing a unique MHC recombinant. After an initial cross to introduce a specific recombinant, 10 backcrosses to the inbred line produced lines with 99.9% genetic uniformity. The current study compared Rous sarcoma virus (RSV) tumor growth in 5 congenic lines homozygous for MHC recombinants (003.R1 = BF24-BG23, 003.R2 = BF2-BG23, 003.R4 = BF2-BG23, 003.R5 = BF21-BG19, and 003.R13 = BF17-BG23). Two experiments used a total of 70 birds from the 5 congenic lines inoculated with 20 pock forming units of RSV subgroup C at 6 wk of age. Tumor size was scored 6 times over 10 wk postinoculation followed by assignment of a tumor profile index (TPI) based on the tumor size scores. Tumor growth over time and rank transformed TPI values were analyzed by least squares ANOVA. Tumor size increased over the experimental period in all genotypes through 4 wk postinoculation. After this time, tumor size increased in Lines 003.R1, plateaued in Lines 003.R2, 003.R4, and 003.R13, and declined in 003.R5. Tumor growth over time was significantly lower in Line 003.R5 compared with all other genotypes. In addition, Line 003.R5 chickens had significantly lower TPI values compared with Lines 003.R2, 003.R4, and 003.R13. The TPI of Line 003.R1 did not differ significantly from any of the other genotypes. The BF21 in Line 003.R5 produced a greater response against subgroup C RSV tumors than did BF24, found in 003.R1; BF2 found in 003.R2 and R4 as well as BF17 found in 003.R13.


Assuntos
Sarcoma Aviário , Animais , Galinhas/genética , Genótipo , Histocompatibilidade , Complexo Principal de Histocompatibilidade/genética , Sarcoma Aviário/genética
4.
J Virol ; 94(12)2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32238588

RESUMO

Tetherin/BST-2 is an antiviral protein that blocks the release of enveloped viral particles by linking them to the membrane of producing cells. At first, BST-2 genes were described only in humans and other mammals. Recent work identified BST-2 orthologs in nonmammalian vertebrates, including birds. Here, we identify the BST-2 sequence in domestic chicken (Gallus gallus) for the first time and demonstrate its activity against avian sarcoma and leukosis virus (ASLV). We generated a BST-2 knockout in chicken cells and showed that BST-2 is a major determinant of an interferon-induced block of ASLV release. Ectopic expression of chicken BST-2 blocks the release of ASLV in chicken cells and of human immunodeficiency virus type 1 (HIV-1) in human cells. Using metabolic labeling and pulse-chase analysis of HIV-1 Gag proteins, we verified that chicken BST-2 blocks the virus at the release stage. Furthermore, we describe BST-2 orthologs in multiple avian species from 12 avian orders. Previously, some of these species were reported to lack BST-2, highlighting the difficulty of identifying sequences of this extremely variable gene. We analyzed BST-2 genes in the avian orders Galliformes and Passeriformes and showed that they evolve under positive selection. This indicates that avian BST-2 is involved in host-virus evolutionary arms races and suggests that BST-2 antagonists exist in some avian viruses. In summary, we show that chicken BST-2 has the potential to act as a restriction factor against ASLV. Characterizing the interaction of avian BST-2 with avian viruses is important in understanding innate antiviral defenses in birds.IMPORTANCE Birds are important hosts of viruses that have the potential to cause zoonotic infections in humans. However, only a few antiviral genes (called viral restriction factors) have been described in birds, mostly because birds lack counterparts of highly studied mammalian restriction factors. Tetherin/BST-2 is a restriction factor, originally described in humans, that blocks the release of newly formed virus particles from infected cells. Recent work identified BST-2 in nonmammalian vertebrate species, including birds. Here, we report the BST-2 sequence in domestic chicken and describe its antiviral activity against a prototypical avian retrovirus, avian sarcoma and leukosis virus (ASLV). We also identify BST-2 genes in multiple avian species and show that they evolve rapidly in birds, which is an important indication of their relevance for antiviral defense. Analysis of avian BST-2 genes will shed light on defense mechanisms against avian viral pathogens.


Assuntos
Proteínas Aviárias/imunologia , Vírus do Sarcoma Aviário/imunologia , Antígeno 2 do Estroma da Médula Óssea/imunologia , Evolução Molecular , Galliformes/imunologia , Sarcoma Aviário/imunologia , Sequência de Aminoácidos , Animais , Proteínas Aviárias/genética , Vírus do Sarcoma Aviário/genética , Vírus do Sarcoma Aviário/patogenicidade , Antígeno 2 do Estroma da Médula Óssea/genética , Linhagem Celular , Fibroblastos/imunologia , Fibroblastos/virologia , Galliformes/genética , Galliformes/virologia , Regulação da Expressão Gênica , Células HEK293 , HIV-1/genética , HIV-1/imunologia , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Passeriformes/genética , Passeriformes/imunologia , Passeriformes/virologia , Sarcoma Aviário/genética , Sarcoma Aviário/virologia , Seleção Genética , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Transdução de Sinais , Liberação de Vírus , Replicação Viral , Produtos do Gene gag do Vírus da Imunodeficiência Humana/genética , Produtos do Gene gag do Vírus da Imunodeficiência Humana/imunologia
5.
Front Biosci (Landmark Ed) ; 24(3): 463-481, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30468667

RESUMO

The present study determines the cytokine gene expression in chickens following RSV-A infection, using RT-qPCR. In susceptible chickens tumors progressed to  fulminating metastatic tumors while it regressed in  regressors  chickens and some resistant non-responder chickens did not respond to RSV-A infection and thus did not develop tumors at all. The in vivo expression of pro-inflammatory cytokines, Th1 cytokines and Th2 cytokines was determined at the primary site of infection, as well as in different organs of progressor, regressor and non-responder chicks at different time intervals. Our results indicated a significant upregulation of the pro-inflammatory cytokines, IL-6 and IL-8, in all the organs of progressor chicks, while they were significantly lower in regressor and non-responder chicks. The expression of the Th1 cytokines IFN-γ and TNF-α was low in all of the organs of the progressor group, except that in  spleen. In contrast, regressor and non-responder groups showed high expression of IFN-γ and TNF-α. Further, there was an early upregulation of the expression of the Th2 cytokine, IL-10, TGF-ß and GM-CSF, in all of the organs of progressors as compared to uninfected control.


Assuntos
Citocinas/imunologia , Vírus do Sarcoma de Rous/imunologia , Sarcoma Aviário/imunologia , Células Th1/imunologia , Células Th2/imunologia , Animais , Galinhas , Citocinas/genética , Expressão Gênica/imunologia , Interações Hospedeiro-Patógeno/imunologia , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Vírus do Sarcoma de Rous/fisiologia , Sarcoma Aviário/genética , Sarcoma Aviário/virologia , Células Th1/metabolismo , Células Th1/virologia , Células Th2/metabolismo , Células Th2/virologia , Regulação para Cima/imunologia
6.
Anim Genet ; 43(3): 348-51, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22486511

RESUMO

The chicken major histocompatibility complex (MHC-B locus) has a strong association with resistance and susceptibility to numerous diseases. We have found a B haplotype designated WLA that associated with the regression of tumours caused by Rous sarcoma virus J strain (RSV-J). Haplotype WLA was identical to the regressive B6 haplotype when partial genotyping was performed (Poultry Science, 89, 2010, 651). We then constructed a bacterial artificial chromosome (BAC) library from a WLA homozygote chicken to evaluate the structure of this regression haplotype and compared it to those of the B6 haplotype. Comparison between WLA and B6 above 59 kb within the 167 kb, including 14 genes from BG1 to BF2, revealed 75 SNPs and 14 indels. However, several genes were identical between WLA and B6, including the BF1 and BF2 genes, which encode a class I molecule previously suggested to be related to the regression phenotype. The BLB2 gene encoding the MHC class II beta chain showed the greatest diversity, with 19 non-synonymous SNPs. A comparison of WLA and B6 haplotpyes that are associated with tumour regression and RIRa and B24 haplotypes associated with tumour progression suggests that DMA1, DMA2, BRD2, TAPBP and BLB2 genes are not involved in the intensity of RSV J tumour regression.


Assuntos
Galinhas/genética , Complexo Principal de Histocompatibilidade/genética , Sarcoma Aviário/genética , Animais , Mapeamento Cromossômico , Cromossomos Artificiais Bacterianos , Marcadores Genéticos , Biblioteca Genômica , Genótipo , Haplótipos/genética , Haplótipos/imunologia , Mutação INDEL , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único , Vírus do Sarcoma de Rous/imunologia , Sarcoma Aviário/imunologia
7.
J Virol ; 86(4): 2021-30, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22171251

RESUMO

The group of closely related avian sarcoma and leukosis viruses (ASLVs) evolved from a common ancestor into multiple subgroups, A to J, with differential host range among galliform species and chicken lines. These subgroups differ in variable parts of their envelope glycoproteins, the major determinants of virus interaction with specific receptor molecules. Three genetic loci, tva, tvb, and tvc, code for single membrane-spanning receptors from diverse protein families that confer susceptibility to the ASLV subgroups. The host range expansion of the ancestral virus might have been driven by gradual evolution of resistance in host cells, and the resistance alleles in all three receptor loci have been identified. Here, we characterized two alleles of the tva receptor gene with similar intronic deletions comprising the deduced branch-point signal within the first intron and leading to inefficient splicing of tva mRNA. As a result, we observed decreased susceptibility to subgroup A ASLV in vitro and in vivo. These alleles were independently found in a close-bred line of domestic chicken and Indian red jungle fowl (Gallus gallus murghi), suggesting that their prevalence might be much wider in outbred chicken breeds. We identified defective splicing to be a mechanism of resistance to ASLV and conclude that such a type of mutation could play an important role in virus-host coevolution.


Assuntos
Alpharetrovirus/fisiologia , Proteínas Aviárias/genética , Galinhas/genética , Predisposição Genética para Doença , Doenças das Aves Domésticas/genética , Splicing de RNA , Receptores Virais/genética , Sarcoma Aviário/genética , Deleção de Sequência , Alpharetrovirus/genética , Sequência de Aminoácidos , Animais , Proteínas Aviárias/metabolismo , Sequência de Bases , Galinhas/metabolismo , Galinhas/virologia , Íntrons , Dados de Sequência Molecular , Doenças das Aves Domésticas/metabolismo , Doenças das Aves Domésticas/virologia , Receptores Virais/metabolismo , Sarcoma Aviário/metabolismo , Sarcoma Aviário/virologia
8.
Poult Sci ; 89(4): 651-7, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20308396

RESUMO

The chicken MHC-B locus affects the response to several strains of Rous sarcoma virus (RSV). We evaluated the association between haplotypes of the MHC-B locus and responses to the J strain of RSV by using an F(2) experimental resource family constructed with tumor-regressive (White Leghorn) and tumor-progressive (Rhode Island Red) chickens. The MHC-B haplotypes were determined by genotyping of the microsatellite marker LEI0258 and MHC-B locus class I alpha chain 2 (BF2). Two haplotypes in the resource family, one associated with tumor regression and one with progression, were defined by these 2 markers. To discriminate more precisely the regressive haplotype in this family, we further developed 35 SNP markers at the MHC-B locus. Information on the haplotypes revealed here should be useful for identifying chickens with regression and progression phenotypes of J-strain RSV-induced tumors.


Assuntos
Galinhas/genética , Complexo Principal de Histocompatibilidade/genética , Sarcoma Aviário/genética , Animais , Mapeamento Cromossômico , Primers do DNA , Marcadores Genéticos , Genótipo , Haplótipos/genética , Haplótipos/imunologia , Polimorfismo de Nucleotídeo Único , Vírus do Sarcoma de Rous/imunologia , Sarcoma Aviário/imunologia
9.
Poult Sci ; 88(8): 1601-7, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19590074

RESUMO

Rous sarcoma virus (RSV)-induced tumor growth was examined in congenic lines of chickens with different major histocompatibility (B) complex recombinant haplotypes on the highly inbred line UCD 003 (B17B17) genetic background. Males bearing an individual B complex recombinant were mated to UCD 003 females followed by 10 backcross generations. Matings among heterozygotes for each recombinant produced homozygous chickens estimated to contain 99.9% of the line UCD 003 background genome. The 5 lines having distinct serologically identified MHC recombinant haplotypes, which arose from separate recombinational events, were as follows: 003.R1, 003.R2, 003.R4, 003. R5, and 003.R6. Chicks from each of the recombinant lines were challenged with 10 pfu subgroup A RSV at 6 wk of age. Tumors were scored for size 6 times over 10 wk postinoculation. Each bird was assigned a tumor profile index (TPI) based on the 6 tumor size scores. Hatch and B genotype were main effects in the statistical analysis. Least squares ANOVA was used to evaluate rank-transformed TPI values and mean tumor sizes through a repeated measures design. Tumor growth and TPI values were greater for 003.R1 and 003.R4 chickens than for the other 3 congenic lines. Among serologically similar recombinants 003.R2 and 003.R4, higher tumor growth and TPI in 003.R4 indicate unique genetic variation affecting RSV tumors compared with 003.R2. The similar tumor growth of 003.R5 and 003.R6 chickens, which have BF/BL21 but different BG regions, demonstrated no BG effect on RSV tumors.


Assuntos
Galinhas/genética , Predisposição Genética para Doença , Complexo Principal de Histocompatibilidade/genética , Doenças das Aves Domésticas/genética , Sarcoma Aviário/genética , Animais , Galinhas/imunologia , Feminino , Genótipo , Masculino , Doenças das Aves Domésticas/imunologia
11.
J Virol ; 82(16): 7818-27, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18550662

RESUMO

Unmethylated CpG islands are known to keep adjacent promoters transcriptionally active. In the CpG island adjacent to the adenosine phosphoribosyltransferase gene, the protection against transcriptional silencing can be attributed to the short CpG-rich core element containing Sp1 binding sites. We report here the insertion of this CpG island core element, IE, into the long terminal repeat of a retroviral vector derived from Rous sarcoma virus, which normally suffers from progressive transcriptional silencing in mammalian cells. IE insertion into a specific position between enhancer and promoter sequences led to efficient protection of the integrated vector from silencing and gradual CpG methylation in rodent and human cells. Individual cell clones with IE-modified reporter vectors display high levels of reporter expression for a sustained period and without substantial variegation in the cell culture. The presence of Sp1 binding sites is important for the protective effect of IE, but at least some part of the entire antisilencing capacity is maintained in IE with mutated Sp1 sites. We suggest that this strategy of antisilencing protection by the CpG island core element may prove generally useful in retroviral vectors.


Assuntos
Vírus da Leucose Aviária/metabolismo , Ilhas de CpG , Inativação Gênica , Sarcoma Aviário/genética , Sarcoma Aviário/virologia , Transcrição Gênica , Animais , Sítios de Ligação , Aves , Citometria de Fluxo , Genes Reporter , Humanos , Modelos Biológicos , Mutação , Vírus do Sarcoma de Rous/metabolismo , Fator de Transcrição Sp1/metabolismo , Sequências Repetidas Terminais
13.
Poult Sci ; 83(4): 638-49, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15109061

RESUMO

The chicken major histocompatibility (B) complex (MHC) affects disease outcome significantly. One of the best characterized systems of MHC control is the response to the oncogenic retrovirus, Rous sarcoma virus (RSV). Genetic selection altered the tumor growth pattern, either regressively or progressively, with the data suggesting control by one or a few loci. Particular MHC genotypes determine RSV tumor regression or progression indicating the crucial B complex role in Rous sarcoma outcome. Analysis of inbred lines, their crosses, congenic lines, and noninbred populations has revealed the anti-RSV response of many B complex haplotypes. Tumor growth disparity among lines identical at the MHC but differing in their background genes suggested a non-MHC gene contribution to tumor fate. Genetic complementation in tumor growth has also been demonstrated for MHC and non-MHC genes. RSV tumor expansion reflects both tumor cell proliferation and viral replication generating new tumor cells. In addition, the B complex controls tumor growth induced by a subviral DNA construct encoding only the RSV v-src oncogene. Immunity to subsequent tumors and metastasis also exhibit MHC control. Genotypes that regressed either RSV or v-src DNA primary tumors had enhanced protection against subsequent homologous challenge. Regressor B genotypes had lower tumor metastasis compared with progressor types. Together, the data indicate that B complex control of RSV tumor fate is strongly defined by the response to a v-src-determined function. Differential RSV tumor outcomes among various B genotypes may include immune recognition of a tumor-specific antigen or immune system influences on viral replication.


Assuntos
Vírus do Sarcoma Aviário/imunologia , Complexo Principal de Histocompatibilidade/imunologia , Doenças das Aves Domésticas/imunologia , Sarcoma Aviário/imunologia , Animais , Vírus do Sarcoma Aviário/classificação , Galinhas , Cruzamentos Genéticos , Feminino , Dosagem de Genes , Masculino , Doenças das Aves Domésticas/genética , Doenças das Aves Domésticas/patologia , Sarcoma Aviário/genética , Sarcoma Aviário/patologia
14.
Gene ; 317(1-2): 209-13, 2003 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-14604810

RESUMO

This article gives a historical insight into the establishment of suitable models allowing the postulation that chicken Rous sarcoma virus (RSV) becomes integrated in different cells as a provirus. This is documented by the correspondence between two laboratories involved in these investigations. Special attention is paid to RSV-transformed mammalian cells, their virogenic nature, virus rescue by cell fusion, and finally their use for the oncogene v-src characterization. Two sets of experiments are mentioned, which provided an early indication of a transforming gene present in RSV.


Assuntos
Vírus do Sarcoma Aviário/genética , Transformação Celular Viral/genética , Genoma Viral , Provírus/genética , Animais , Vírus do Sarcoma Aviário/enzimologia , Vírus do Sarcoma Aviário/crescimento & desenvolvimento , Linhagem Celular Transformada , Galinhas , História do Século XX , Vírus Oncogênicos/genética , Vírus Oncogênicos/crescimento & desenvolvimento , DNA Polimerase Dirigida por RNA/genética , DNA Polimerase Dirigida por RNA/história , DNA Polimerase Dirigida por RNA/metabolismo , Ratos , Sarcoma Aviário/genética , Sarcoma Aviário/história , Sarcoma Aviário/virologia
15.
Exp Biol Med (Maywood) ; 227(3): 158-63, 2002 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11856813

RESUMO

This study was designed to examine the alloantigen system L effects on Rous sarcomas in three B complex genotypes. The parental stock was 50% Modified Wisconsin Line 3 x White Leghorn Line NIU 4 and 50% inbred Line 6.15-5. Pedigree matings of two B(2)B(5) L(1)L(2) sires to five B(2)B(5) L(1)L(2) dams per sire produced experimental chicks segregating for B and L genotypes. Chicks were inoculated with 20 pock-forming units (pfu) of Rous sarcoma virus (RSV) at 6 weeks of age. Tumors were scored six times over 10 weeks postinoculation after which the tumor scores were used to assign a tumor profile index (TPI) to each chicken. Tumor growth over time and TPI were evaluated by repeated-measures analysis of variance and analysis of variance, respectively. Six trials were conducted with a total of 151 chickens. The major histocompatibility (B) complex affected the responses as the B(2)B(2) and B(2)B(5) genotypes had significantly lower tumor growth over time and TPI than the B(5)B(5) genotype. Separate analyses revealed no significant L system effect in B(2)B(2) or B(2)B(5) backgrounds. However, L genotype significantly affected (P < 0.05) both tumor growth over time and TPI in B(5)B(5) chickens. B(5)B(5) L(1)L(2) birds had TPI significantly lower than B(5)B(5) L(1)L(1) chickens but not B(5)B(5) L(2)L(2). Mortality was lower in the B(5)B(5) L(1)L(2) birds than in B(5)B(5) L(2)L(2) chickens. The L system, or one closely linked, affects the growth and ultimate outcome of Rous sarcomas. The response may depend upon the genetic background as well as MHC type.


Assuntos
Galinhas , Antígenos de Histocompatibilidade/imunologia , Sarcoma Aviário/imunologia , Animais , Predisposição Genética para Doença , Haplótipos , Antígenos de Histocompatibilidade/genética , Prognóstico , Sarcoma Aviário/genética , Sarcoma Aviário/mortalidade , Sarcoma Aviário/fisiopatologia
17.
Philos Trans R Soc Lond B Biol Sci ; 355(1400): 1077-84, 2000 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-11186309

RESUMO

In contrast to the major histocompatibility complex (MHC) of well-studied mammals such as humans and mice, the particular haplotype of the B-F/B-L region of the chicken B locus determines life and death in response to certain infectious pathogens as well as to certain vaccines. We found that the B-F/B-L region is much smaller and simpler than the typical mammalian MHC, with an important difference being the expression of a single class I gene at a high level of RNA and protein. The peptide-binding specificity of this dominantly expressed class I molecule in different haplotypes correlates with resistance to tumours caused by Rous sarcoma virus, while the cell-surface expression level correlates with susceptibility to tumours caused by Marek's disease virus. A similar story is developing with class II beta genes and response to killed viral vaccines. This apparently suicidal strategy of single dominantly expressed class I and class II molecules may be due to coevolution between genes within the compact chicken MHC.


Assuntos
Galinhas/genética , Galinhas/imunologia , Predisposição Genética para Doença , Complexo Principal de Histocompatibilidade , Vacinas Virais/imunologia , Animais , Vírus do Sarcoma Aviário/patogenicidade , Herpesvirus Galináceo 2/patogenicidade , Doença de Marek/genética , Doença de Marek/imunologia , Sarcoma Aviário/genética , Sarcoma Aviário/imunologia
18.
Poult Sci ; 79(12): 1736-40, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11194035

RESUMO

Major histocompatibility (B) complex haplotypes B(Q) and B17 were examined for their effect on Rous sarcoma outcome. Pedigree matings of B(Q)B17 chickens from the second backcross generation (BC2) of Line UCD 001 (B(Q)B(Q)) mated to Line UCD 003 (B17B17) produced progeny with genotypes B(Q)B(Q), B(Q)B17, and B17B17. Six-week-old chickens were injected with subgroup A Rous sarcoma virus (RSV). The tumors were scored for size at 2, 3, 4, 6, 8, and 10 weeks postinoculation. A tumor profile index (TPI) was assigned to each bird based on the six tumor scores. Two experiments with two trials each were conducted. In Experiment 1, chickens (n = 84) were inoculated with 30 pock-forming units (pfu) RSV. There was no significant B genotype effect on tumor growth over time or TPI among the 70 chickens that developed tumors. Chickens (n = 141) were injected with 15 PFU RSV in Experiment 2. The B genotype significantly affected tumor growth pattern over time in the 79 chickens with sarcomas. The B(Q)B17 chickens had the lowest TPI, which was significantly different from B17B17 but not B(Q)B(Q). The data indicate complementation because more tumor regression occurs in the B(Q)B17 heterozygote than in either B(Q)B(Q) or B17B17 genotypes at a 15 pfu RSV dose and significantly so compared to B17B17. By contrast, the 30 pfu RSV dose utilized in the first experiment overwhelmed all genotypic combinations of the B(Q) and B17 haplotypes, suggesting that certain MHC genotypes affect the immune response under modest levels of viral challenge.


Assuntos
Galinhas/genética , Complexo Principal de Histocompatibilidade/genética , Doenças das Aves Domésticas/virologia , Sarcoma Aviário/genética , Alelos , Animais , Vírus do Sarcoma Aviário , Cruzamentos Genéticos , Genótipo , Haplótipos , Sarcoma Aviário/patologia , Sarcoma Aviário/virologia
19.
Vet Res Commun ; 23(1): 53-68, 1999 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-10905818

RESUMO

A study using two high-performance broiler lines, a synthetic male line (SML) and a synthetic dam line (SDL), was undertaken to investigate the pattern of mortality due to induced liver tumours (LT) and the immune response to subgroup A virus inoculated via the chorioallantoic membrane (CAM) route. The distribution patterns of the four possible phenotypes were similar in both sire and dam lines. The occurrence of conversely associated phenotypes was about 30S, in both the lines. The percentages of CAM(+) LT(-) and CAM(-) LT(+) were 14.26%, and 14.46% in the dam line and 20.0% and 9.57% in the male line. The LT mortality was 30-50% in the birds with low pock counts, whereas it was 80-93% in the birds with high pock counts. The group specific antigen shedding status did not influence death due to LT. In birds in the high pock count group, 98% of deaths due to LT were completed by the sixth week, whereas in those in the low pock count group, death due to LT was spread over 24 weeks. The SDL birds survived better than SML birds in the high pock count groups. In both lines, about 20% of deaths occurred owing to non-specific causes. The average survival time after hatching before death from LT was 26 days, whereas that for non-specific death was 81 days.


Assuntos
Vírus do Sarcoma Aviário/imunologia , Galinhas/genética , Neoplasias Hepáticas/veterinária , Sarcoma Aviário/mortalidade , Albuminas/análise , Animais , Vírus do Sarcoma Aviário/patogenicidade , Distribuição de Qui-Quadrado , Embrião de Galinha , Galinhas/crescimento & desenvolvimento , Galinhas/imunologia , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , Predisposição Genética para Doença/genética , Histocitoquímica , Análise dos Mínimos Quadrados , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/virologia , Masculino , Sarcoma Aviário/genética , Sarcoma Aviário/imunologia , Sarcoma Aviário/virologia , Estatísticas não Paramétricas
20.
Vet Immunol Immunopathol ; 66(2): 143-57, 1998 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-9860187

RESUMO

The influence of the chicken major histocompatibility (B) complex (MHC) on the adherence potential of monocyte-derived macrophages was examined using the congenic chicken lines CB and CC. These lines represent well-defined genetic models for the study of resistance (CB) or susceptibility (CC) to the progressive growth of Rous sarcomas. Using a monoclonal antibody specific for chicken monocytes/macrophages, CB and CC chickens were shown by flow cytometry analyses to have similar proportions of peripheral blood monocytes. However, when the glass-adherence potential of these cells was compared during incubation in tissue culture medium over 24, 48 and 72 h at 40 degrees C, significant differences were seen between cells from these two inbred lines. After 24 and 48 h, glass-adherence by CB cells was 2-3 fold higher than that of CC cells. After 72 h this difference decreased to 1.5 fold. At 24 and 48 h, the adherent CB macrophages also appeared about 1.5 times larger than those of CC chickens. Genetic analysis using F1 hybrids (CBxCC) showed that this trait is regulated by a dominant gene that segregates with the B12 haplotype in the backcross generation F1xCC. From the results obtained with the recombinant congenic lines CB.R1 and CC.R1, we conclude that the gene regulating adherence potential is localized within the B-F/L region of the chicken MHC. About 50% of adherent cells were able to phagocytose opsonised FITC-labelled Zymosan particles. The level of nitric oxide production in vitro by CB and CC macrophages was equal. The importance of cells of the mononuclear phagocyte system for the response to Rous sarcoma virus (RSV) infection was studied in CB chickens using the anti-macrophage agents silica, carrageenan, and C12MDP, encapsulated in liposomes. In those chickens treated with silica and carrageenan, we observed progressive growth of RSV-induced tumors. The graft-versus-host reactivity of peripheral blood lymphocytes (PBL) of treated chickens was comparable to controls. In vitro nitric oxide production by macrophages from silica-treated chickens was higher than by macrophages from untreated controls.


Assuntos
Vírus do Sarcoma Aviário/imunologia , Galinhas/genética , Complexo Principal de Histocompatibilidade/genética , Monócitos/imunologia , Sarcoma Aviário/genética , Animais , Anticorpos Monoclonais/farmacologia , Carragenina/farmacologia , Carragenina/uso terapêutico , Adesão Celular , Galinhas/imunologia , Ácido Clodrônico/farmacologia , Ácido Clodrônico/uso terapêutico , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , Citometria de Fluxo/veterinária , Regulação da Expressão Gênica , Reação Enxerto-Hospedeiro/imunologia , Haplótipos , Macrófagos/citologia , Macrófagos/imunologia , Complexo Principal de Histocompatibilidade/imunologia , Masculino , Monócitos/citologia , Óxido Nítrico/biossíntese , Fagocitose/imunologia , Sarcoma Aviário/imunologia , Dióxido de Silício/farmacologia , Dióxido de Silício/uso terapêutico , Zimosan/farmacologia
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