Reticuloendotheliosis in Poultry

Reticuloendotheliosis virus is immunologically, morphologically, and structurally distinct from the leukosis/sarcoma group of avian retroviruses. The International Committee on Taxonomy of Viruses has classified reticuloendotheliosis viruses within the family Retroviridae, subfamily Orthoretrovirinae, genus Gammaretrovirus. Although all isolates belong to a single serotype, three subtypes of reticuloendotheliosis virus have been identified on the basis of neutralization tests and differential reactivity with monoclonal antibodies. Strains can be further classified by their ability to replicate in cell culture. Most field isolates appear to be nondefective for replication in cell cultures and contain no viral oncogene. One unique laboratory strain (strain T) is defective for replication in cell cultures and contains a viral oncogene, v-rel, that is responsible for an acute reticulum cell neoplasia in experimentally inoculated chicks; this neoplasm prompted the name reticuloendotheliosis but is not commonly seen in the field.

Horizontal transmission of reticuloendotheliosis virus is probably more important than vertical, although both have been documented in chickens and turkeys. Transmission by mosquitoes and other blood-sucking insects is suspected. The virus has been isolated from litter. A high rate of congenital infection has been demonstrated in naturally infected turkeys, but such flocks are probably rare. The virus has been transmitted accidentally through use of contaminated vaccines. Most commonly, however, flocks seroconvert after 10 weeks of age without clinical disease or viral shedding to progeny. Experimentally, contact transmission occurs, but the virus is neither highly contagious nor highly stable in the environment. Partial or complete genomic insertion of reticuloendotheliosis virus in the genome of other avian viruses, namely fowlpox and Marek's disease viruses, has been described. However, the significance of such insertion in transmission of reticuloendotheliosis virus is not known. Although semen from tolerantly infected turkeys contains infectious virus, the role of the tom in vertical transmission is not clear.

The nondefective strains of reticuloendotheliosis virus produce three distinct syndromes: non-neoplastic runting, acute neoplastic disease, and chronic neoplastic disease resulting in B and T lymphomas. Typically, the runting syndrome is seen 4–10 weeks after administration of contaminated vaccines to day-old chicks, which can lead to dramatic economic losses. Chronic neoplastic disease has been induced experimentally in chickens, turkeys, and ducks; one type occurs in chickens after latent periods of >4 months and appears identical to lymphoid leukosis. As in lymphoid leukosis, these tumors are composed of B cells, are bursal-dependent, and have IgM on their surface. Acute neoplasia, which occurs after a latent period of 6–8 weeks, also has been seen in chickens, turkeys, ducks, and quail. This tumor in chickens involves T cells and may be confused with Marek's disease.

The clinical findings for runting syndrome include weight loss, paleness, occasional paralysis, and abnormal feathering (Nakanuke disease). Death from acute or chronic neoplasia is preceded by depression and occasionally by some of the same clinical changes described for the runting syndrome.

The abnormal feather lesion, in which the barbules are compressed to the shaft over a small part of its length, may be of diagnostic value. Other lesions include bursal and thymic atrophy, enlarged nerves, and anemia. Neoplasms typically involve the liver, spleen, intestine, and heart. The bursa is involved in the chronic B-cell lymphomas of chickens in a manner similar to that of lymphoid leukosis. Nonbursal (T-cell) lymphomas with shorter latent periods and lesions superficially resembling those of Marek's disease also are recognized in chickens. In turkeys, prominent lesions include enlarged livers and nodular lesions on the intestines; the bursa is only rarely tumorous. The tumors, regardless of type or host species, are usually composed of uniform, large, lymphoreticular cells.

• Standard criteria: history and clinical signs, gross pathology, and histopathology

• Advanced criteria: immunohistochemistry, standard and quantitative PCR, virus isolation, serology

Because lesions induced by reticuloendotheliosis virus are so diverse and resemble so closely those of other tumors, diagnosis at necropsy is difficult. A diagnosis of reticuloendotheliosis requires not only the presence of typical gross and microscopic lesions but also the demonstration of reticuloendotheliosis virus. Because reticuloendotheliosis virus is not yet as ubiquitous as avian leukosis and Marek's disease viruses, the demonstration of infectious virus, viral antigens, and proviral DNA in tumor cells has significant diagnostic value. The nerve lesions are usually less extensive and may contain more plasma cells than in Marek's disease but in other cases are difficult to differentiate by histology. The runting syndrome is easily confused with immunosuppressive syndromes caused by other viral agents.

The chronic B-cell lymphomas induced experimentally in chickens cannot easily be distinguished from those of lymphoid leukosis except by virus studies, including PCR. Similarly, the T-cell lymphomas of chickens cannot easily be distinguished from Marek's disease except by virus studies. Techniques based on immunocytochemistry with monoclonal antibodies to cellular, tumor, and viral antigens or molecular hybridization can be used in the differential diagnosis of avian viral lymphomas, including reticuloendotheliosis. Both B- and T-cell lymphomas induced by reticuloendotheliosis virus contain a clonally integrated DNA provirus usually associated with the c-myc oncogene, which can be demonstrated by appropriate molecular methods. The chronic lymphomas that are seen in turkeys must be differentiated from lymphoproliferative disease of turkeys based on histology, virus isolation, and characterization of the virus-associated reverse transcriptase for activity in the presence of manganese or magnesium ions.

• There is currently no treatment or commercial vaccine available for reticuloendotheliosis

• Principles used to control avian leukosis virus could be used but generally are not applied to reticuloendotheliosis in commercial practice because of low prevalence

No control measures for reticuloendotheliosis are currently practiced. An experimental recombinant fowlpox virus vaccine has been developed. Some breeder companies wish to avoid seroconversion of their primary breeder stocks to obviate restrictions on export of progeny to certain countries, but reliable techniques to prevent horizontal transmission have not been developed. Elimination of vertical transmission would presumably be possible by removing potential transmitter hens; rearing progeny under isolated conditions would prevent horizontal infection. Many of these principles have successfully been applied to the control of avian leukosis virus in chickens. Such control procedures could be considered if reticuloendotheliosis virus infection becomes endemic in especially valuable breeding stock, as was the case with reticuloendotheliosis virus infection in the endangered Attwater’s prairie chickens.

• Tumor Diagnosis Manual available from the AAAP