Reticuloendotheliosis is a neoplastic disease of poultry caused by reticuloendotheliosis virus. Reticuloendotheliosis bursal lymphomas are virtually identical to lymphoid leukosis B-cell lymphomas. Reticuloendotheliosis nonbursal lymphoma, a T-cell lymphoma, has been observed under laboratory conditions but has not been reported in the field. Standard criteria used for diagnosis include history, clinical signs, gross necropsy, and histological examination. No treatment or vaccine is currently available.
Reticuloendotheliosis designates a group of neoplastic and immunosuppressive syndromes in several avian species caused by reticuloendotheliosis virus, a member of the avian retrovirus group. The host range of reticuloendotheliosis virus is much broader than that of Marek's disease or avian leukosis. Natural infection and disease occur in chickens, turkeys, ducks, geese, and quail; probably many species of birds can be infected. Mammals appear refractory, although certain mammalian cell cultures are susceptible.
Reticuloendotheliosis virus is not as ubiquitous as Marek's disease and avian leukosis viruses but is more widely distributed than once believed. Some cases have been attributed to accidental contamination of live virus poultry vaccines such as Marek's disease virus and fowlpox virus with reticuloendotheliosis virus. Although clinical outbreaks are not frequently observed, serological surveys suggest that the virus is prevalent in both chicken and turkey flocks in many countries, including the US.
Etiology of Reticuloendotheliosis in Poultry
Reticuloendotheliosis virus is antigenically, 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 are able to replicate in cell culture and lack a 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 observed in the field.
Pathogenesis of Reticuloendotheliosis in Poultry
Reticuloendotheliosis virus produces three distinct syndromes: nonneoplastic runting, acute neoplastic disease, and chronic neoplastic disease resulting in B and T lymphomas.
Typically, the runting syndrome, which can lead to dramatic economic losses, is observed 4–10 weeks after administration of contaminated vaccines to day-old chicks.
Acute neoplasia, which occurs after a latent period of 6–8 weeks, also has been observed in chickens, turkeys, ducks, and quail. This tumor in chickens involves T cells and may be confused with Marek's disease.
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.
Epidemiology of Reticuloendotheliosis in Poultry
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; however, such flocks are probably rare. The virus has been transmitted accidentally through use of contaminated vaccines. Most commonly, however, flocks seroconvert after 10 weeks old without clinical signs of disease or viral shedding to progeny.
Experimentally, contact transmission occurs; however, 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 importance 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.
Clinical Findings and Lesions of Reticuloendotheliosis in Poultry
The clinical findings for runting syndrome in reticuloendotheliosis include weight loss, paleness, occasional paralysis, and abnormal feathering (Nakanuke disease). Death from acute or chronic neoplasia is preceded by listlessness 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 cloacal 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 cloacal bursa is only rarely tumorous. The tumors, regardless of type or host species, are usually composed of uniform, large, lymphoreticular cells.
Diagnosis of Reticuloendotheliosis in Poultry
Standard criteria: history and clinical signs, gross pathological changes, and histological examination
Advanced criteria: immunohistochemical testing, standard and quantitative PCR assay, virus isolation, serological testing
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 appreciable 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 histological examination. The runting syndrome is easily confused with immunosuppressive syndromes due to 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 assay. Similarly, the T-cell lymphomas of chickens cannot easily be distinguished from Marek's disease except by virus studies. Techniques based on immunocytochemical testing with monoclonal antibodies against 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 in turkeys must be differentiated from lymphoproliferative disease of turkeys based on histological examination, virus isolation, and characterization of the virus-associated reverse transcriptase for activity in the presence of manganese or magnesium ions.
Control of Reticuloendotheliosis in Poultry
No treatment or commercial vaccine
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; however, 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.
Key Points
Reticuloendotheliosis virus can cause both B-cell and T-cell lymphomas.
Presumptive diagnosis can be made based on history, clinical signs, gross pathological changes, and histological examination, although viral detection methods are of greater value compared with other avian tumor viruses because of lower prevalence in the field.
No treatment or commercial vaccine is currently available.
For More Information
Zavala G, Nair V. Reticuloendotheliosis. In: Swayne DE, ed. Boulianne M, Logue CM, McDougald LR, Nair V, Suarez DL, associate eds. Diseases of Poultry. 14th ed. Wiley; 2019:587-625.
Witter RL, Gimeno IM, Pandiri AR, Fadly AM. Tumor Diagnosis Manual: The Differential Diagnosis of Lymphoid and Myeloid Tumors in the Chicken. American Association of Avian Pathologists; 2010.
