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sequence and analysis of the bamhi "d" fragment of shope fibroma virus: comparison with similar regions of related poxviruses.differences observed in the virulence of two related leporipoxviruses are closely tied to a particular region of their genomes. for the virulent poxvirus of this pair, malignant rabbit fibroma virus (mv), this region is the bamhi "c" fragment, which is 10.7 kb. for the avirulent poxvirus, shope fibroma virus, sfv, this region is the corresponding bamhi "d" fragment, which is 13.1 kb. as part of our attempt to understand the virulence of these two viruses, we sequenced these two dna fragments. th ...19921329373
transcriptional mapping of early rna from regions of the shope fibroma and malignant rabbit fibroma virus genomes.malignant rabbit fibroma virus (mv) is a recombinant poxvirus derived from shope fibroma virus (sfv) and rabbit myxoma virus (d. s. strayer, e. skaletsky, g. f. cabirac, p. a. sharp, l. b. corbeil, s. sell, and j. l. leibowitz, 1983a, j. immunol. 130, 399-404; w. block, c. upton, and g. mcfadden, 1984, virology 140, 113-124). we report here the transcriptional mapping of early rnas transcribed from the sfv sequences within mv and from the corresponding regions in sfv. hybridization analysis and ...19863016986
sequence and analysis of a portion of the genomes of shope fibroma virus and malignant rabbit fibroma virus that is important for viral replication in lymphocytes.the 10.7-kb bamhi "c" restriction fragment of malignant rabbit fibroma virus (mv) contains genes that are important for its immunosuppressive activity. when this fragment is transferred to a related avirulent leporipoxvirus, shope fibroma virus (sfv), recombinant viruses show clinical features characteristic of mv: they replicate in lymphocytes and alter immune function in vitro, induce disseminated tumors in recipient rabbits, and are immunosuppressive in vivo. the 10.7-kb bamhi "c" restriction ...19911660196
regulation of p53 gene expression by a poxviral transcription factor.identification of regulators of p53 expression is a crucial step in understanding the diverse functions of p53 and its role in cellular homeostasis and responsiveness to insult. several viral proteins inactivate p53 as a modulator of cell cycle progression and apoptosis. here, we report that a unique leporipoxviral transcription factor greatly increases levels of p53 mrna. c7, an early transcription factor from malignant rabbit fibroma virus (mv), is an important determinant of mv virulence. its ...19968862400
myxoma virus expresses a secreted protein with homology to the tumor necrosis factor receptor gene family that contributes to viral virulence.poxviruses are known to contain a large number of open reading frames, particularly near the termini of the viral genome, that are not required for growth in tissue culture. however, many of these gene products are believed to play important roles in determining the virulence of the virus by modulating the host immune response to the infection. recently it has been shown that shope fibroma virus encodes, within the terminal inverted repeats, a protein (t2) related to the cellular tumor necrosis ...19911651597
virus-induced loss of class i mhc antigens from the surface of cells infected with myxoma virus and malignant rabbit fibroma virus.shope fibroma virus (sfv) is a leporipoxvirus that causes localized benign fibromas in immunocompetent adult rabbits that spontaneously regress due, in part, to a cell-mediated immune response. myxoma virus (myx) and malignant rabbit fibroma virus (mrv) are related leporipoxviruses that induce rapidly lethal generalized infections accompanied by tumors and immunosuppression. because only these latter two viruses are known to compromise cell-mediated antiviral responses, cell surface levels of cl ...19921309843
deletion of the growth factor gene related to egf and tgf alpha reduces virulence of malignant rabbit fibroma virus.the role of the epidermal growth factor homologue in malignant rabbit fibroma virus (mrv) pathogenicity was investigated by constructing a viral growth factor deletion mutant (mrv-gf-). since mrv is a recombinant virus with a myxoma virus background but possesses some terminal sequences derived from shope fibroma virus, the growth factor gene in mrv is in fact identical to shope fibroma growth factor (sfgf). although no significant differences were detected in the in vitro characteristics of mrv ...19921309274
a 34-kd protein with strong homology to ras-like proteins inhibits epidermal growth factor activity.epidermal growth factor (egf) and its analog, transforming growth factor-alpha, are felt to be important in oncogenesis. when malignant rabbit fibroma virus infects rk-13 rabbit kidney cells, a 34-kd protein that inhibits the effects of egf on certain target cell lines is produced. we have purified this protein using high-pressure liquid chromatography and gel electrophoresis. this purified protein abolishes egf-induced cellular proliferation. it also causes the egf receptor-bearing a431 carcino ...19938475991
inhibition of plasmin, urokinase, tissue plasminogen activator, and c1s by a myxoma virus serine proteinase inhibitor.the myxoma and malignant rabbit fibroma poxviruses are lethal tumorigenic viruses of rabbits whose virulence is modulated by the production of a virus-encoded secreted serine proteinase inhibitor, serp-1. this viral protein was detected in medium harvested from myxoma and malignant rabbit fibroma virus-infected cells, and its inhibitory profile has been characterized by gel and kinetic analysis. serp-1 forms complexes with and inhibits the human fibrinolytic enzymes plasmin, urokinase, and two-c ...19938416956
transforming growth factor alpha, shope fibroma growth factor, and vaccinia growth factor can replace myxoma growth factor in the induction of myxomatosis in rabbits.the epidermal growth factor (egf) homologues encoded by vaccinia virus, myxoma virus, and malignant rabbit fibroma virus have been shown to contribute to the pathogenicity of virus infection upon inoculation of susceptible hosts. however, since the primary structures of these growth factors and the disease profiles induced by different poxvirus genera vary substantially, the degree to which the various egf homologues perform similar roles in viral pathogenesis remains unclear. in order to determ ...19938380671
effect of virus infection on levels of transcripts for cellular genes.malignant rabbit fibroma virus (mv) induces tumors composed of proliferating cells, principally fibroblasts, and vasculature. these tumors are associated with large amounts of collagen and other connective tissue proteins. we studied the effect of mv infection on levels of mrna for alpha 1 chains of collagens type i, iii and v in rk-13 fibroblasts and alpha 2 chain of collagen type i. mv infection induces expression of specific collagen genes at particular time points after infection in vitro. e ...19938109159
immunologic dysfunction during viral oncogenesis. ii. inhibition of cellular immunity to viral antigens by malignant rabbit fibroma virus.the ability of two related viruses--shope fibroma virus (sfv) and malignant rabbit fibroma virus (mv)--to induce virus-specific immune responses in lymphocytes of recipient animals was studied. sfv produces a benign local tumor which regresses in 12-14 days. using an assay for virus-induced lymphocyte blastogenesis lymphocytes reactive to sfv were detected, both in rabbits bearing sfv-induced tumors and in rabbits whose sfv-induced tumor had regressed. these virus-reactive cells were detected in ...19846327086
malignant rabbit fibroma virus: observations on the culture and histopathologic characteristics of a new virus-induced rabbit tumor.the clinical, histopathologic, and cultural characteristics of a newly isolated poxvirus, malignant rabbit fibroma virus (mv), were investigated. mv was isolated from tumors induced by an uncloned stock of shope fibroma virus (sfv). mv, sfv, and rabbit myxoma virus were compared. similarly to myxoma virus, mv grew to higher titer in vitro than did sfv and produced plaques rather than foci on rabbit kidney cell monolayers. unlike the local, self-limited fibroblastic proliferations observed in sfv ...19836306326
immunohistology of malignant rabbit fibroma virus--a comparative study with rabbit myxoma virus.malignant rabbit fibroma virus (mv) causes a syndrome that consists of disseminated malignant tumors and immunosuppression complicated by severe pasteurella multocida infection and death. tissues from rabbits given mv and rabbit myxoma virus were examined by direct immunofluorescence with the use of antibody against virus antigens. primary and metastatic tumors caused by mv and rabbit myxoma virus were composed of soft tissue cells containing virus antigens. skin appendages and epidermis overlyi ...19836306322
malignant rabbit fibroma virus causes secondary immunosuppression in rabbits.shope fibroma virus (sfv) causes a localized, self-limited, fibroblastic proliferation in adult rabbits. extracts of shope fibroma tumors were found to contain a second virus that induces a rapidly progressive disseminated tumor. dissemination of this malignant fibroma is associated with activation of commensal mucosal infection with pasteurella multocida, causing purulent conjunctivitis and rhinitis and resulting in death from nasal obstruction. we have isolated this new agent by two cycles of ...19836292305
immunologic dysfunction during viral oncogenesis. i. nonspecific immunosuppression caused by malignant rabbit fibroma virus.malignant rabbit fibroma virus (mv) is a potent oncogenic poxvirus that produces a rapidly progressive syndrome of disseminated myxosarcoma, immunosuppression, and fatal gram-negative infection. mv is probably a recombinant between shope fibroma virus (sfv) and rabbit myxoma virus, and is capable of preventing or aborting the in vitro proliferative responses of rabbit lymphocytes to b and t lymphocyte mitogens. proliferative responses to sheep erythrocytes (srbc) are similarly affected, although ...19836195270
inhibition of epidermal growth factor-induced cellular proliferation.the authors tested whether two oncogenic poxviruses, shope fibroma virus (sfv) and malignant rabbit fibroma virus (mv), coded for an epidermal growth factor (egf)-like protein. virus-free lysates of sfv or mv-infected rabbit kidney cells do not appreciably affect proliferation of egf-unresponsive rk-13 cells. comparable lysates inhibit the background proliferation of two egf-responsive cell lines, human foreskin fibroblasts and normal rat kidney cells. inhibition of egf-stimulated proliferation ...19873039847
growth of malignant rabbit fibroma virus in lymphoid cells.to understand better the immunosuppressive capacity of malignant rabbit fibroma virus (mv), we characterized mv growth in lymphoid cells. replication of mv occurs in unstimulated normal spleen cells in vitro and is enhanced by adding t- or b-lymphocyte mitogens. in splenic t-lymphocyte preparations, comparable results are found: virus growth in the absence of mitogen, augmented by adding con a. unlike mature t cells, thymic lymphocytes support mv replication only when mitogen is added. when sple ...19873033886
virus-lymphocyte interactions during the course of immunosuppressive virus infection.malignant rabbit fibroma virus (mv) is a lymphocytotropic leporipoxvirus which produces profound immunological dysfunction and lethal fibromyxosarcoma. we examined virus recovery from splenic lymphocytes as a function of time after inoculation in vivo, and correlated this with both immunological function and expression of virus-induced host suppressor activity. mv was most abundant in lymphocytes obtained 4 days following inoculation. at that time, immune function was relatively normal and host ...19873029285
inhibition of virus replication does not alter malignant rabbit fibroma virus-induced immunosuppression.malignant rabbit fibroma virus (mv) directly suppresses generation of antibody responses and mitogen induced t and b lymphocyte proliferation. we investigated whether this phenomenon required expression of the complete viral genome. phosphonoacetic acid (paa) inhibits poxvirus specific dna polymerases. adding paa to cultures reduces both mv replication and mitogen-driven rabbit lymphocyte proliferation in a dose-dependent fashion. a dose of paa adequate to inhibit mv replication by about 97%, bu ...19863026700
immunosuppression in viral oncogenesis. iii. effects of virus infection on interleukin 1 and interleukin 2 generation and responsiveness.malignant rabbit fibroma virus (mv) is an oncogenic immunosuppressive leporipoxvirus. we studied the effects of mv infection and mv-associated tumor-induced suppressor factor (tisf) on the production of and responsiveness to interleukins 1 and 2. adherent cells from mv tumor-bearing rabbits elaborate adequate amounts of il 1 in response to e. coli endotoxin. neither live virus nor tisf alters the production or the responsiveness to il 1. however, when we examined spleen cells from rabbits 7 days ...19863023485
reversal of virus-induced immune suppression.we studied the immunosuppressive capacity of splenic lymphocytes from rabbits at different stages of progressive myxosarcoma induced by malignant rabbit fibroma virus (mv). spleen cells taken from rabbits 7 days after virus inoculation proliferate poorly in response to con a, and suppress normal responses to the mitogen. those from animals 11 days after virus injection have recovered partially from mv-induced suppression. further, their con a responses are no longer suppressed by day 7 spleen ce ...19863005416
in vitro growth of two related leporipoxviruses in lymphoid cells.we examined the in vitro growth patterns of two leporipoxviruses, malignant rabbit fibroma virus (mv) and shope fibroma virus (sfv), in lymphoid cells. mv replicates well in normal spleen cells in vitro. at low m.o.i. (0.001), dramatic virus growth occurs in unstimulated cell cultures. this growth is enhanced by addition of the t lymphocyte mitogen, concanavilin a, or the b lymphocyte mitogen, escherichia coli lipopolysaccharide. shope fibroma virus does not grow in lymphocytes in culture, with ...19852992155
tumorigenic poxviruses: transcriptional mapping of the terminal inverted repeats of shope fibroma virus.a composite transcriptional map for the entire 12.4-kb terminal inverted repeat (tir) region of the shope fibroma virus (sfv) genome has been determined. northern blotting and s1-nuclease mapping were used to determine the regions which are transcribed, their temporal relationships, as well as the transcriptional initiation sites. sequences representing the entire tir are transcribed into poly(a)+ mrna at both early and late times in the infection. fifteen transcriptional initiation sites were m ...19872884778
tumorigenic poxviruses: fine analysis of the recombination junctions in malignant rabbit fibroma virus, a recombinant between shope fibroma virus and myxoma virus.malignant rabbit fibroma virus (mrv) has been shown to be a lethal tumorigenic poxvirus of rabbits derived from a recombination event between shope fibroma virus (sfv), which induces benign fibromas in rabbits, and myxoma virus, the agent of myxomatosis. we have cloned and sequenced all of the mrv recombination junctions, which are located near the left and right terminal inverted repeat (tir) regions, and present a composite map of the mrv genome with respect to the relevant gene products. the ...19882842947
immunosuppression during viral oncogenesis. v. resistance to virus-induced immunosuppressive factor.rabbits given malignant rabbit fibroma virus (mv) develop severe immunologic dysfunction during the course of infection. splenic t lymphocytes from these rabbits elaborate a soluble non-specific immunosuppressive factor (virus-induced suppressor factor (visf]. as malignant rabbit fibroma virus infection progresses, normal immunologic responsiveness returns. this recovery is multi-factorial and involves production by t lymphocytes of a soluble factor capable of antagonizing the activity of visf. ...19882837511
immunosuppression during viral oncogenesis. iv. generation of soluble virus-induced immunologic suppressor molecules.we describe herein functional attributes and generation of immunologic suppressor activity elaborated in response to oncogenic virus infection. malignant rabbit fibroma virus-induced immunologic suppressor factor (visf) is a t cell product produced in peak quantities by spleen cells taken from infected rabbits 7 days after infection in vivo. its production does not appear to require macrophage participation. visf is highly labile, 3.5 to 12 kda, and capable of suppressing both b and t lymphocyti ...19882831278
myxoma virus and malignant rabbit fibroma virus encode a serpin-like protein important for virus virulence.the leporipoxviruses shope fibroma virus (sfv), the myxoma virus (myx), and the sfv/myx recombinant malignant rabbit fibroma virus (mrv) are closely related yet induce profoundly different diseases in the european rabbit. sfv, which produces a benign tumor at the site of inoculation, is cleared by the immune system after approximately 2 weeks whereas myx and mrv induce a rapidly lethal systemic infection characterized by generalized suppression of host immune functions. dna sequencing studies re ...19902173255
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