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PubMed2000

Avian reticuloendotheliosis virus strain A and spleen necrosis virus do not infect human cells.

Spleen necrosis virus (SNV) and Reticuloendotheliosis virus strain A (REV-A) belong to the family of reticuloendotheliosis viruses and are 90% sequence related. SNV-derived retroviral vectors produced by the REV-A-based D17.2G packaging cell line were shown to infect human cells (H.-M. Koo, A. M. C. Brown, Y. Ron, and J. P. Dougherty, J. Virol. 65:4769-4776, 1991), while similar vectors produced by another SNV-based packaging cell line, DSH134G, are not infectious in human cells (reviewed by R. Dornburg, Gene Ther. 2:301-310, 1995). Here we describe a careful reevaluation of the infectivity of vectors produced from the most commonly used REV-A- or SNV-based packaging cells obtained from various sources with, among them, one batch of D17.2G packaging cells obtained from the American Type Culture Collection. None of these packaging cells produced vectors able to infect human cells. Thus, contrary to previously published data, we conclude that REV-based vectors are not infectious in human cells.

Cell Separation↗
PubMed1971

Separation of reticuloendotheliosis virus from avian tumor viruses.

Velocity sedimentation and isopycnic density gradient centrifugation indicate that reticuloendotheliosis virus has a different mass and buoyant density than members of the avian tumor virus group. The group-specific antigen of the avian tumor virus group was not detected in concentrated and purified reticuloendotheliosis virus preparations.

Alpharetrovirus↗
PubMed1983

Construction of a helper cell line for avian reticuloendotheliosis virus cloning vectors.

We wished to construct cell lines that supply the gene products of gag, pol, and env for the growth of replication-defective reticuloendotheliosis retrovirus vectors without production of the helper virus. To do this, first we located by S1 mapping the donor and acceptor splice sites of reticuloendotheliosis virus strain A. The donor splice site is ca. 850 base pairs from the 5' end of proviral DNA. It is close to or overlaps the encapsidation sequences for viral RNA. The splice acceptor site is ca. 5.6 kilobase pairs from the 5' end of proviral DNA. Therefore, the encapsidation sequences and the donor splice site were removed from viral DNA to give expression of the gag and pol genes without virus production. The promoter in the long terminal repeat was fused to a site near the first ATG codon of the env gene, thereby deleting the encapsidation sequences and the gag and pol genes to give expression of the env gene without virus production. The permissive canine cell line D17 was transfected with the two modified viral DNAs. Two cell clones that contain both modified viral DNAs support the production of replication-defective spleen necrosis virus-thymidine kinase recombinant retrovirus vectors without the production of helper virus. To prevent recombination, the vector contains deletions that overlap with deletions in the integrated helper virus DNAs. This helper cell-vector system will be useful to derive infectious recombinant virus stocks of high titer (over 10(5) thymidine kinase transforming units per ml) which are able to infect avian, rat, and dog cells without the aid of helper virus.

Animals↗
PubMed2003

Reticuloendotheliosis viruses and derived vectors for human gene therapy.

The reticuloendotheliosis viruses (REV) spleen necrosis virus (SNV) and reticuloendotheliosis virus strain-A (REV-A) are amphotropic retroviruses which infect a large variety of cells of avian and some mammalian species. They normally do not infect primate or rodent cells. However, they efficiently infect and integrate their genome into that of human cells when they are pseudotyped with the envelope protein of other mammalian retroviruses or the G protein of vesicular stomatitis virus (VSV) or rabies viruses (RV). Moreover, SNV-derived retroviral vectors, which display single chain antibodies or other targeting ligands on the viral surface enable cell-type-specific gene delivery into various human cells. My laboratory has developed genetically engineered REV vectors, which are capable of infecting non-dividing cells such as quiescent human T-cells, primary monocyte-derived macrophages, and mature neurons. Thus, REV-derived vectors appear to be very interesting candidates for the further development of vectors for human gene therapy. This article reviews the replication of REVs and vectors derived from REV-A and SNV for gene transfer into human cells.

Animals↗
PubMed1989

Histomoniasis and reticuloendotheliosis in a wild turkey (Meleagris gallopavo) in North Carolina.

A moribund wild turkey (Meleagris gallopavo) died shortly after it was discovered in Martin County, North Carolina (USA). The 4.3-kg female turkey appeared in good condition with no visible external lesions or evidence of injury. There were 2- to 5-mm yellow-white plaques on the mucosal surfaces of the oral cavity and mid-esophagus. The liver had large, multifocal, irregular pale areas on cut and uncut surfaces. The spleen contained multifocal, pale, hard, nodules. Microscopic changes in the liver consisted of large multifocal coalescing areas of necrosis. Occasional spherical 10 to 15 microns in diameter organisms consistent with Histomonas meleagridis were present in the necrotic areas. Viable hepatic parenchyma contained multifocal infiltrations of numerous mononuclear cells interpreted as neoplastic cells resembling lymphoblasts and plasma cells. Similar neoplastic cell infiltrates, consistent with the lymphoproliferative disease reticuloendotheliosis, were present in spleen, lung, and esophageal and oral mucosa. Reticuloendotheliosis virus, subtype 2, was isolated from samples of liver and spleen.

Animals↗
PubMed1984

Reticuloendotheliosis virus and disturbance in immune regulation.

Reticuloendotheliosis virus (REV-T) is a replication-defective retrovirus which induces a rapidly-fatal lymphoma. The helper virus, reticuloendotheliosis-associated virus (REV-A), induces a splenic suppressor cell population which cytostatically inhibits the proliferation of cytotoxic cells capable of lysing REV-T tumour cells.

Animals↗
PubMed1982

Morphological, immunological, and biochemical analyses of chicken spleen cells transformed in vitro by reticuloendotheliosis virus strain T.

Reticuloendotheliosis virus strain T (REV-T) is a highly oncogenic avian retrovirus which causes a rapid neoplastic disease of the lymphoreticular system. We derived six cell lines (1-3, 1-5, 2-10, 2-14, 2-16, and 2-20) from chicken spleen cells infected with REV-T. These cells can produce both the REV-T and its associated reticuloendotheliosis helper virus, REV-A. Histochemical analyses of these cells indicate that, while they are not stained by benzidine, peroxidase, beta-glucuronidase or acid alpha-naphthyl acetate esterase, they contain a high proportion (95%) of cells positive for acid phosphatase. Light and electron microscopic studies of these cells also revealed morphologies of lymphoblasts or activated lymphocytes with irregular nuclei and dispersed chromatin. Immunochemical analyses indicate that essentially all (90 to 100%) of the cells contain the surface marker Ia, but no cytoplasmic immunoglobulin M and immunoglobulin G could be detected by immunofluorescence staining. Results also show that some of these cell lines contain a low level of terminal transferase (0.02 to 0.17 unit/10(9) cells), and a proportion (3 to 35%) of these cells can be stained by an antiserum directed against chicken bursa cells. These results are consistent with the conclusion that the cells transformed by the highly oncogenic REV-T are lymphoid in nature. In addition, at least some of these cell clones may contain features characteristic of activated B-lymphocytes. Analysis of these cell clones indicates that some cell lines contain an adherent and nonadherent population with some differences in morphologies. In addition, electron microscopic examination revealed that, while the non-adherent cells are actively producing type C viruses, type C viruses are either absent or very rare in the adherent cell populations. These results support the conclusion that some of these cell lines are heterogeneous and contain subpopulations of cells with differences in their ability to produce viruses.

Animals↗
PubMed1995

Detection of antibodies to avian leukosis/sarcoma viruses (ALSV) and reticuloendotheliosis viruses (REV) in humans by ELISA.

We used a modified commercial ELISA kit to test for antibodies to avian leukosis/sarcoma and reticuloendotheliosis viral antigens in the sera of 45 poultry workers and their matched controls. We found that 42% of sera from poultry workers had anti-avian leukosis Sarcoma viruses (anti-ALSV) and 20% had anti-reticuloendotheliosis viruses (anti-REV), antibody titers that were higher than the highest titer recorded in control subjects, and hence were regarded as positive. To determine the specificity of these reactions, selected sera were absorbed with ALSV or REV antigens alone, or with chick embryo fibroblasts (CEF) alone, or with both CEF and ALSV/REV, and then retested. In each case, absorption resulted in a statistically significant reduction in absorbance, which was greatest for the combined CEF and ALSV/REV absorption, thus suggesting that the reactions involved viral as well as chicken antigens. However, definitive tests such as Western Blot analyses are needed to confirm whether indeed antibodies to these viruses were specifically elicited in human sera.

Antibodies, Viral↗
PubMed1998

Orbital lymphosarcoma associated with reticuloendotheliosis virus in a peafowl.

Lymphosarcoma associated with infection by avian reticuloendotheliosis virus was diagnosed in an Indian peafowl with exophthalmia and exposure keratitis. Exenteration of the orbit was complicated by a profound oculocardiac reflex and extensive hemorrhage during surgery. Orbital bleeding was controlled by direct pressure, electrocautery, topical administration of bovine thrombin, and application of sterile gelatin sponges and oxidized regenerated cellulose. A blood transfusion was also performed. In addition to describing methods of handling intraoperative complications of orbital exenteration in birds, to the authors' knowledge, this is the first report to describe an association of reticuloendotheliosis virus, which more commonly affects poultry, with lymphosarcoma in an Indian peafowl.

Animals↗
PubMed1975

Leukemic reticuloendotheliosis. A study of the origin of the malignant cell.

A highly pure preparation of neoplastic cells from the spleen of a patient with leukemic reticuloendotheliosis was studied for function, membrane characteristics and glucose metabolism. Glass adherence and phagocytosis of small particles (latex and carbon black) were demonstrated with phase contrast microscopy. Staphylocidal activity was similar to that of normal monocytes. Immunofluorescent assays revealed nonspecific uptake of antiserums to immunoglobulins G (IgG), M (IgM), A (IgA) and kappa and kappa and lambda light chains. Rosette assays indicated the presence of receptors for IgG on the surface of all cells but no receptors for complement (C3) or sheep red blood cells. Glucose metabolic studies revealed a pattern that differed from that of normal monocytes or lymphocytes with intermediate values for glycolysis, low hexose monophosphate shunt activity and high Krebs cycle activity. Increments in tritiated (3H)-thymidine uptake and glucose metabolism in response to phytohemagglutinin stimulation were minimal (5 per cent of normal lymphocyte values) and no response was noted with pokeweed mitogen stimulation. These findings suggest that the leukemic reticuloendotheliosis cell most closely resembles cells of the monocyte-histiocyte series.

Cell Separation↗
PubMed1976

Leukemic reticuloendotheliosis. A failure of monocyte production.

In five cases of leukemic reticuloendotheliosis studied, profound monocytopenia was demonstrable. In 48 normal subjects, monocyte counts ranged from 215 to 921 per cubic millimeter, whereas in the five patients with leukemic reticuloendotheliosis, the counts ranged from 0 to 17 per cubic millimeter. The properties of the "hairy" cell are consistent with those of an incompletely developed monocyte. The susceptibility to infection, characteristics of these patients, may result from a lack of normal monocytes in blood and tissues.

Adult↗
PubMed1976

Naturally occurring reticuloendotheliosis in turkeys: transmission.

This report describes the natural occurrence and experimental transmission of reticuloendotheliosis in a turkey flock. In the naturally affected turkeys, lesions were present in the liver, spleen, heart, intestines, and peripheral nerves, and were composed mainly of lymphoreticular cells. The disease was experimentally reproduced in turkey poults with cellfree tissue extracts of infected birds. A type-C RNA virus similar to reticuloendotheliosis virus (strain T) was present in the tissues of turkey poults experimentally inoculated. This virus was unrelated to the type-C RNA viruses of the avian leukosis sarcoma complex.

Animals↗
PubMed1980

Legionnaires' disease in leukaemic reticuloendotheliosis.

At our hospital 15 cases of leukaemic reticuloendotheliosis and 4 cases of legionnaires' disease have been diagnosed. 3 patients had both diseases. The clinical findings are reported. It is probable that patients with leukaemic reticuloendotheliosis have an increased susceptibility to Legionnaires' disease. Possible reasons for the decreased resistance are discussed.

Aged↗
PubMed1967

Replication of the reticuloendotheliosis virus (strain T) in chicken embryo cell culture.

Investigations were conducted on the in vitro replication of the reticuloendotheliosis (RE) virus (strain T) in specific-pathogen-free chicken embryo fibroblast (CEF) cultures. Active virus production was detected in the tissue culture fluid 24 hr after infection. When injected into chickens, samples taken 42 hr after infection of the cell cultures killed approximately 50% of the birds at a 1:100 dilution. The RE virus titer remained at this level for 5 days before declining. Cell-free virus preparations from tissue cultures rarely resulted in 100% mortality of the assay birds. The level of cell-associated virus was very low. Evidence that the reticuloendotheliosis was not induced by a mycoplasma was indicated by failure to isolate an organism on PPLO Agar (Difco) and failure of kanamycin or amphotericin B to inhibit multiplication of RE virus in vitro. RE virus appeared to be unrelated to members of the avian leukosis and sarcoma complex. It did not induce resistance in CEF cultures to sarcoma viruses of the A or B subgroup of this complex. Similarly, preinfection of cell cultures with leukosis viruses of the A or B subgroup did not inhibit or reduce the replication of RE virus.

Alpharetrovirus↗
PubMed1973

Lack of serological relationship among DNA polymerases of avian leukosis-sarcoma viruses, reticuloendotheliosis viruses, and chicken cells.

Antibodies against a large and a small DNA polymerase isolated from chicken embryos and against avian myeloblastosis virus DNA polymerase were used to study the serological relationships of the DNA polymerase activities of three avian systems with RNA and a DNA polymerase-avian leukosis-sarcoma viruses, reticuloendotheliosis viruses, and a fraction from uninfected chicken cells. The DNA polymerase activity of disrupted virions of all avian leukosis-sarcoma viruses tested was neutralized to the same extent by antibody against avian myeloblastosis virus DNA polymerase and was not neutralized by the antibodies against chicken cellular DNA polymerases. The viruses tested included induced leukosis viruses and Rous-associated virus-O. The DNA polymerase activity of disrupted virions of all of the reticuloendotheliosis viruses was not neutralized by any of the antibodies. The chicken endogenous RNA-directed DNA polymerase activity was neutralized partially or completely, in different experiments, by antibody against the small DNA polymerase isolated from chicken embryos, but was not neutralized by the other two antibodies.

Alpharetrovirus↗
PubMed1974

Infectious rous sarcoma virus and reticuloendotheliosis virus DNAs.

An efficient and quantitative assay for infectious Rous sarcoma virus and reticuloendotheliosis virus DNAs is described. The specific infectivities of viral DNA corresponded to one infectious unit per 10(5) to 10(6) viral DNA molecules. Infection with viral DNA followed one-hit kinetics. The minimal size of infectious Rous sarcoma virus DNA was approximately 6 million daltons, whereas the minimal size of infectious reticuloendotheliosis virus DNA was larger, 10 to 20 million daltons.

Animals↗
PubMed1992

Reticuloendotheliosis type C and primate type D oncoretroviruses are members of the same receptor interference group.

The reticuloendotheliosis viruses (REVs), originally isolated from avian species, constitute a group of retroviruses which are more closely related to mammalian retroviruses than to other avian retroviruses. The envelope glycoproteins of members of the REV group display a striking amino acid sequence identity with a group of primate oncoretroviruses which belong to a single receptor interference group and include all of the type D and some type C primate oncoretroviruses. Members of the REV group also have a broad host range which covers most avian cells and some mammalian cells, including those of simian and human origin. In view of this broad host range and the envelope sequence similarities, we investigated the cross-interference pattern between REV and primate virus groups to determine whether they utilized the same receptor. Superinfection experiments using a vector virus containing an Escherichia coli lacZ gene showed that reticuloendotheliosis and simian oncoretroviruses constitute a single receptor interference group on both human and canine cells and indicate that the viruses bind to the same receptor to initiate infection. These results suggest that this receptor binding specificity has been maintained over a wide range of retroviruses and may be responsible for the broad spread of these retroviruses between different orders of vertebrates.

Amino Acid Sequence↗