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PubMedDate not supplied

Tolerance, viral shedding, and neoplasia in chickens infected with non-defective reticuloendotheliosis viruses.

Chickens inoculated as embryos with non-defective reticuloendotheliosis viruses (ndREVs) generally developed a "tolerant" infection characterized by lack of immunofluorescent antibody and by a viremia that persisted through 93 weeks. Chickens inoculated at hatching generally developed a "non-tolerant" infection characterized by antibody development that gradually waned as the chickens aged and by a transient or intermittent viremia. Although chickens tolerantly infected with ndREV strain T were immunodepressed, tolerance to ndREVs did not depend on immunodepression, because 17-to-20-week-old chickens tolerantly infected with ndREV strain CS were normal in antibody response to sheep red blood cells and Brucella abortus and in mitogen-stimulated blastogenesis of blood lymphocytes. Tolerantly infected dams shed low levels of gs antigen and virus into eggs at high frequencies; however, in two trials, congenital transmission of virus by strain-CS-infected dams was documented in only 2 of 42 and 1 of 132 progeny chicks. Eggs and progeny chicks from non-tolerantly infected dams were always negative for virus and gs antigen. After long latent period (17 to 93 weeks), ndREV-infected chickens developed lymphomas involving the bursa of Fabricius and other visceral organs at high frequency and developed sarcomas, carcinomas, and inflammatory nerve lesions at a lower frequency. The ability of ndREVs to induce tolerant and non-tolerant infection, virus- and antigen-shedding into eggs, and chronic neoplastic disease resembled that of lymphoid leukosis virus, another common avian retrovirus. Certain differences in epidemiological properties of these 2 viruses are discussed.

Animals↗

PubMedDate not supplied

In vitro and in vivo investigations on reticuloendotheliosis virus infection.

Experimental transmission of reticuloendotheliosis (RE) in 1-day-old SPF chickens was achieved by intraperitoneal inoculation of cell-associated and cell-free RE virus (REV). REV-inoculated chickens exhibited an immune response throughout the entire observation period. Viremia persisted for 5--6 months in chickens hatched from REV-inoculated SPF embryonated eggs. The natural occurrence of RE was detected in turkey flocks of farms Bc.

Animals↗

PubMedDate not supplied

Effect of endogenous leukosis virus genes on response to infection with avian leukosis and reticuloendotheliosis viruses.

We examined the effect of the presence or absence of endogenous viral gene (ev) 3, which controls expression of group-specific viral and envelope antigens (gs+chf+ phenotype), and ev2, which controls the production of a complete subgroup E virus (V-E+ phenotype), on the response of chickens to RAV-1, an exogenous avian leukosis virus (ALV) with an antigenic relationship to endogenous virus. After inoculation at one day of age, the chickens lacking either ev gene expression had a lower frequency of virus isolations and higher frequency and titer of neutralizing antibodies than those expressing ev genes. This relationship was not seen in groups inoculated with chick syncytial virus (CSV), a reticuloendotheliosis-associated virus with no relationship to endogenous virus, but the ev2+ birds tended to yield more CSV isolations than the ev2- birds. We suggest that chickens expressing ev genes may be immunologically tolerant to antigens common to exogenous and endogenous viruses. In addition, ev3- birds inoculated with RAV-1 at one day of age or as embryos died at a high rate between 6 and 12 weeks of age with a non-neoplastic syndrome characterized by severe atrophy of lymphoid organs, an inflammatory reaction in the liver, and a lower immune response to particulate antigens.

Animals↗

PubMedDate not supplied

Detection of antibodies against reticuloendotheliosis viruses by an enzyme-linked immunosorbent assay.

A microplate indirect enzyme-linked immunosorbent assay (ELISA) for antibodies against reticuloendotheliosis virus (REV) was consistently more sensitive than indirect immunofluorescent-antibody tests. Limits of antibody detection were comparable to those obtained in virus neutralizations. Detection of REV-infected chickens long after infection and after immunofluorescent antibody has waned makes ELISA especially suitable for screening chicken flocks.

Animals↗

PubMedDate not supplied

Cytopathic effects and focus formation by reticuloendotheliosis viruses in a quail fibroblast cell line.

The T and CS (chick syncytial) strains of reticuloendotheliosis virus (REV) induced focus formation and cytonecrotic changes in a Japanese quail fibroblast cell line designated QT35. The focus was distinctive and readily discernible, consisting of rounded refractile and larger dark-appearing (syncytia) cells usually aggregated along the periphery of a hole within a focus. The foci and cytopathic effects induced by the two strains of REV were morphologically indistinguishable. The focus formation in QT35 cultures was inhibited by chicken antiserum against the homologous or heterologous strain of REV; the homologous antiserum induced a greater inhibition. The altered cells composed of focus exhibited cytoplasmic fluorescence when stained by an indirect fluorescent-antibody technique with either the homologous or heterologous anti-REV serum. When foci that developed in QT35 cultures maintained under fluid medium were enumerated 3 days postinoculation, there were a highly significant correlation (P less than 0.001) and a linear relationship between the number of foci developed and relative virus concentration inoculated, thus justifying the validity of focus assay of REV by this system. The QT35 cell line may provide a useful in vitro system for virological and serological studies of REV.

Animals↗

PubMedDate not supplied

Studies of reticuloendotheliosis virus-induced lymphomagenesis in chickens.

Seventy-three percent of chickens inoculated with the chick syncytial strain of reticuloendotheliosis virus (REV) at hatching developed lymphomas by 39 weeks of age. Neonatal treatment with cyclophosphamide or surgical bursectomy at 2, 4, 8, or 12 weeks of age significantly (P less than 0.01) reduced lymphoma development. In a further experiment, surgical bursectomy of REV-infected chickens followed by intravenous inoculation of the chickens with a single cell suspension of their own bursa cells at 2, 4, 9, or 13 weeks of age resulted in lymphoid tumors in chickens treated at 9 or 13 weeks but not in chickens treated at 2 or 4 weeks of age. Furthermore, this treatment did not shorten the incubation period for lymphoma development. These findings argue very strongly that transforming target cells are primarily in the bursa of Fabricius. The data also suggest that a minimum residency of 4 weeks in the bursa is required for infected bursa cells to become transformed. Therefore, lymphomagenesis induced by REV in chickens appears similar to that induced by the avian leukosis virus group.

Animals↗

PubMed1983

Effect of reticuloendotheliosis virus on the response of chickens to Salmonella typhimurium infection.

Groups of 25 chickens free of maternal antibody to reticuloendotheliosis virus (REV) were inoculated with either third or seventh passage REV at either one or seven days of age. Some of the birds inoculated at day 1 with REV were inoculated with Salmonella typhimurium either concurrently or six or 13 days later while some of those inoculated with REV at day 7 were inoculated concurrently with S typhimurium. At day old, infection with S typhimurium alone caused the death of 12 of 25 chicks whereas in the dual infection, using the third passage REV, 18 of 25 birds died. Similarly no seven or 14 day old chickens died when challenged with S typhimurium alone, but previous day-old infection with REV caused a respective mortality of eight of 25 and five of 25 birds. With the seventh passage REV a similar pattern was seen. At day old S typhimurium infection alone killed seven of 25 birds whereas combined with virus the mortality was 14 of 25 and while S typhimurium alone killed none of 25 chicks infected at seven days old, the mortality in birds also infected with REV was 14 of 25. Combined virus and bacterial infections did not increase the proportion of feathering defects in birds surviving S typhimurium infections. There was a significantly higher proportion of feathering defects in birds infected with third passage virus compared with seventh passage virus. Although a higher proportion of birds had antibody responses to REV in the seventh than in the third passage group, there was no discernible difference in the effect the different viruses had on chickens' susceptibility to S typhimurium.

Animals↗

PubMed1983

Relative efficiency of techniques for detecting avian reticuloendotheliosis virus as a vaccine contaminant.

Three techniques were compared for sensitivity in detecting reticuloendotheliosis virus (REV) in a deliberately contaminated Marek's disease vaccine. The most sensitive and rapid test was the indirect fluorescent antibody test (FAT). The indirect immunoperoxidase test, although simple to perform and only marginally less sensitive than the FAT, was difficult to interpret at low levels of REV. Using immunoelectron microscopy, virions were seen only after three subcultures and then not to the same level as that detected by the FAT or immunoperoxidase test. Serum raised against the HPRS-1 strain of REV detected other strains of this virus in the FAT.

Animals↗

PubMedDate not supplied

Pathogenesis of reticuloendotheliosis virus infection in ducks.

A new isolate of reticuloendotheliosis virus (REV) from ducks, RU-1, was used to experimentally infect white pekin ducks. Embryonal or neonatal infection usually resulted in persistent viremias, no REV antibody development, and inability to mount antibody responses against bovine serum albumin (BSA) or sheep red blood cells (SRBC). In contrast, infection at 21 days of age resulted in transient viremias, which terminated coincident with REV antibody development. These ducks remained persistently infected, however, based on virus isolations from peripheral blood lymphocytes. Ducks infected at that age were immunologically competent against BSA and SRBC unless they had been embryonally bursectomized, in which case they behaved virologically and immunologically like those infected at an early age. Bursectomy by itself did not prevent responses against the antigens. Total mortality during 4- or 6-month experimental periods ranged from 80 to 100% in REV-infected groups, regardless of age at infection, route of exposure, or whether the ducks were intact or bursectomized. Most deaths were from non-neoplastic conditions (stunting, bacterial infections), but 17 of 69 (25%) infected ducks developed a variety of neoplasms, including lymphosarcomas, histiocytic sarcomas, and spindle-cell sarcomas.

Animals↗

PubMedDate not supplied

Improved focus assay of reticuloendotheliosis virus in a quail fibroblast cell line (QT35).

Reticuloendotheliosis virus (REV) strains T and CS consistently induced focus formation in a quail fibroblast cell line designated QT35 that was maintained under agarose overlay following inoculation of REV. The foci were more distinct and better circumscribed than those that developed in QT35 cultures under fluid medium. The focus formation in QT35 cultures under agarose overlay was inhibited by REV antiserum, and there were a highly significant correlation (r = 0.966, P less than 0.005) and a linear relationship between the number of foci that developed and relative virus concentration inoculated. This provides a valid focus assay for REVs.

Animals↗

PubMed1995

Reticuloendotheliosis viruses and derived vectors.

In most human gene therapy trials, the tools of gene delivery are retroviral vectors. All current vectors are derived from murine leukemia virus (MLV). Although this system is suitable for delivering a large variety of genes into different tissues, it also has its limitations and is not adequate for all potential applications of human gene therapy. Thus, attempts are underway in many laboratories to develop other gene delivery tools. Potential agents range from non-viral based gene delivery systems (eg liposomes) to other viral vectors such as those derived from adenoviruses, adeno-associated viruses, herpes simplex virus, and several other viruses. Furthermore, the development of other, non-MLV retroviral vector systems, including one derived from HIV, is in progress in several laboratories. In this article, reticuloendotheliosis viruses and their vector systems are reviewed, and their possible use in human gene therapy is discussed.

Animals↗

PubMedDate not supplied

An immunoperoxidase plaque assay for reticuloendotheliosis virus and its application to a sensitive serum neutralization assay.

A rapid assay for the enumeration of reticuloendotheliosis virus (REV) is described. Chicken embryo fibroblast monolayer cultures were infected with REV and incubated 6 days under an agar overlay. After removal of the overlay, cells were fixed with acetone/ethanol. Foci of infection (hereafter referred to as plaques) were detected using either an anti-REV envelope monoclonal antibody or convalescent chicken serum as the primary antibody; the secondary antibody was either horseradish peroxidase-conjugated goat anti-mouse IgG (for use with monoclonals) or goat anti-chicken IgG (for use with chicken serum). Staining with a substrate solution containing diaminobenzidine, CoCl2, and H2O2 revealed individual dark plaques on a light gray background. This method worked equally well for the SNV, CSV, and REV-T strains of REV; further, it detected all six field isolates tested. Results indicate that this immunoperoxidase technique is a rapid and reliable method for detection and titration of REV as well as for the assay of neutralizing antibody in chicken serum.

Animals↗

PubMed1995

Detection of antibodies to avian leukosis/sarcoma viruses and reticuloendotheliosis viruses in humans by western blot assay.

Serologic evidence of antibodies in humans to avian leukosis/sarcoma viruses (ALSV) and reticuloendotheliosis viruses (REV) has in general been negative. Because of the difficulty in infecting mammalian cells in vitro with these viruses, it is generally held that they do not infect humans. We first provided presumptive evidence of serologic response to these viruses in human sera of workers in poultry slaughtering plants, using an ELISA. We now provide confirmatory evidence using Western blot assay. Our results show that exposed poultry workers and subjects with no occupational exposure to these viruses have antibodies in their sera specifically directed against ALSV p27, p19, p15, and p12 antigens. In addition, we demonstrate evidence of serologic response to REV. This is the first time definitive evidence of exposure to ALSV or REV has been demonstrated in human sera. The significance of this is not known. Further investigation into whether these findings mean that virus has been integrated into the human genome is needed, to assess the public health implications of these results.

Animals↗

PubMedDate not supplied

Comparative evaluation of in vitro and in vivo assays for the detection of reticuloendotheliosis virus as a contaminant in a live virus vaccine of poultry.

Indirect immunofluorescence (IFA), polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay (ELISA) were used for detection of reticuloendotheliosis virus (REV) as a contaminant in a live virus fowl pox (FP) vaccine of poultry. A FP vaccine known to be contaminated with REV was tested by in vitro and in vivo assays in chicken embryo fibroblasts (CEFs) and day-old specific-pathogen-free (SPF) chicks, respectively. Using in vitro assays, IFA and PCR were more sensitive than ELISA in detection of REV in CEFs inoculated with REV-contaminated FP vaccine. However, when the vaccine was tested by in vivo assays using SPF chickens, the sensitivity of ELISA was comparable with that of IFA and PCR. Antibody to REV was not detected in SPF chickens within 4 wk postinoculation with REV-contaminated FP vaccine at hatch. Filtration of vaccine to eliminate vaccine virus from the inoculum before testing in CEFs resulted in a significant reduction in the frequency of REV detection by PCR or IFA. The data suggest that the sensitivity of IFA, PCR, and ELISA depends on the concentration of REV in the vaccine and that in vivo assays of vaccines for contamination with REV should include a test for virus because a negative antibody test may be misleading.

Animals↗

PubMed1978

Leukemic reticuloendotheliosis. Loss of platelet defect after splenectomy.

A 59-year-old woman with leukemic reticuloendotheliosis had pancytopenia and hypersplenism. Before splenectomy, she had an abnormal bleeding time and a severe defect of secondary-wave platelet aggregation. After splenectomy, the platelet count returned to normal, and the aggregation defect was no longer present. This response suggests that the spleen may contribute to the platelet dysfunction.

Blood Platelets↗

PubMed1975

The platelet in leukemic reticuloendotheliosis. Functional and morphological evidence of a qualitative disorder.

Platelets were studied in a group of 10 patients with typical clinical course, morphological findings, and specific histochemical criteria for leukemic reticuloendotheliosis. In 8 of these, marked qualitative abnormalities were found. These included lack of aggregation following epinephrine stimulation (6 patients), and decreased platelet factor 3 availability following ADP stimulation (4 patients). In addition, platelets in 4 of the 10 patients were studied by electron microscopy. All had granular abnormality, and 1 case showed the presence of rough-surfaced endoplasmic reticulum. The functional and ultrastructural abnormalities of platelets reported here may be responsible for the clinically important bleeding episodes which were not attributable to thrombocytopenia in 2 of our patients. The findings also provide a clue to the basic nature of this histogenetically controversial malignancy.

Adenosine Diphosphate↗

PubMed1976

The heterogeneity of leukemic reticuloendotheliosis, "hairy cell leukemia". Evidence for its monocytic origin.

The presence of B, T, and monocyte markers were studied on the spleen and peripheral blood mononuclear cells from two patients with leukemic reticuloendotheliosis. A high proportion of cells from both patients bore a receptor for cytophilic antibody, both in suspension and frozen tissue section. Cells in suspension lacked surface immunoglobulins or a receptor for sheep red blood cells. These results favor the evidence that "hairy cells" are monocytic in origin.

Animals↗

PubMed1978

Leukemic reticuloendotheliosis: polyclonal surface immunoglobulin on "hairy" cells.

The cytochemistry, surface markers and functional properties of purified mononuclear cells obtained from the peripheral blood and spleen of a patient with leukemic reticuloendotheliosis were studied. Nonspecific esterase activity, a monocyte marker, was demonstrable in 83% of the peripheral blood mononuclear cells and 84% of the splenic mononuclear cells. Rosetting techniques failed to detect T or B lymphocyte surface markers on the majority of the cells. Direct immunofluorescence revealed capped, noncytophilic surface immunoglobulin on the cells with all immunoglobulin classes being detectable. Since noncapping conditions ahd been used during immunofluorescence staining, the observed caps were attributed to in vivo binding of autoantibodies to the "hairy" cells. This conclusion was supported by the demonstration of susceptibility of the "hairy" cells to lysis mediated by normal allogeneic lymphocytes. It is postulated that the "hairy" cells in this patient are leukemic monocytes which bear autoantibodies directed against leukemia associated antigens.

Antibodies, Neoplasm↗