Lymphoid leukosis occurs naturally only in chickens. Experimentally, some of the viruses of the leukosis/sarcoma group can infect and produce tumors in other species of birds or even mammals. The infection is known to occur in virtually all chicken flocks except for some SPF flocks from which it has been eradicated. The frequency of infection has been reduced substantially in the primary breeding stocks of several commercial poultry breeding companies. In recent years this control program has expanded, and infection has become infrequent or absent in certain commercial flocks. The frequency of lymphoid leukosis tumors even in heavily infected flocks is typically low (<4%), and disease is often inapparent.
Etiology:Lymphoid leukosis is caused by certain members of the leukosis/sarcoma group of avian retroviruses. Isolates that can induce lymphoid leukosis in chickens are commonly called avian leukosis viruses and belong to subgroups A, B, C, D, and J. Subgroups A and B are most prevalent in western countries. Subgroup J virus has been isolated in England from broiler breeder stocks experiencing myeloid neoplasms (myelocytoma). A sixth subgroup (E) designates nononcogenic endogenous viruses produced by viral genes integrated into the host cell DNA. The subgroups have distinct antigenicities and cellular host ranges that are determined by viral envelope glycoproteins. Some antigenic variation, demonstrated by cross-neutralization, also occurs within subgroups. All field strains of lymphoid leukosis virus are oncogenic, although some differences in oncogenicity and replicative ability have been recognized.
Transmission and Epidemiology:Lymphoid leukosis virus is shed by the hen into the albumen or yolk, or both; infection probably occurs after the onset of incubation. Congenitally infected chickens fail to produce neutralizing antibodies and usually remain viremic for life. Horizontal infection after hatching is also important, especially when chicks are exposed immediately after hatching to high doses of virus, eg, in feces of congenitally infected chicks or in contaminated vaccines. Horizontally infected chickens have a transient viremia followed by antibody production. The earlier the infection, the more likely it is to lead to tolerance and persistent viremia and to tumors. Other factors known to increase the susceptibility of chicks to horizontal infection include the absence of maternal antibodies and the presence of endogenous retroviruses, especially those associated with the slow feathering (K) gene. Tumors are more frequent in congenital than in horizontal infections, but many more chickens are exposed horizontally than congenitally. Rates of embryo transmission typically are 1-10%; virtually all chicks in an infected flock are exposed by contact. Congenital and, in some cases, early horizontal infection can induce permanent carrier states characterized by shedding of virus or antigen into the environment and into eggs. Late infection (ie, inoculation at 12-20 wk of age) is unlikely to lead to virus shedding. The virus is not highly contagious compared with other viral agents and is readily inactivated by disinfectants. Transmission can be reduced or eliminated by strict sanitation. After the infection is eradicated, standard disease control and sanitation practices can keep chicken flocks free of the disease.
Pathogenesis:Lymphoid leukosis is a clonal malignancy of the bursal-dependent lymphoid system. Transformation invariably occurs in the intact bursa, often as early as 4-8 wk after infection. Tumors require some time to develop. Death rarely occurs before 14 wk of age and is more frequent around the time of sexual maturity. The disease can be prevented, even up to 5 mo of age, by treatments that destroy the bursa. The tumors are composed almost entirely of B lymphocytes that, in many instances, have IgM on their surfaces. No antitumor immune response has been recognized. Antibodies are readily induced after infection, except when tolerance occurs.
The induction of lymphoid leukosis tumors can be enhanced in chickens co-infected with serotype 2 Marek’s disease virus, a common vaccine virus. The mechanisms of this enhancement are still under study but require a genetically susceptible chicken and early infection with lymphoid leukosis virus in addition to serotype 2 Marek’s disease vaccination. Because most commercial chicken strains are resistant and lymphoid leukosis virus infection has been largely eradicated from susceptible stocks, enhancement is not currently recognized as a field problem.
A subclinical disease syndrome characterized by depressed egg production in the absence of tumor formation is more important economically than are deaths from lymphoid leukosis. Chickens with subclinical disease usually shed virus or viral antigen into the albumen of eggs. The pathogenic mechanisms are poorly understood.
Clinical Findings and Lesions:Birds with lymphoid leukosis have few typical clinical signs. Infected birds become depressed before death. Palpation often reveals an enlarged bursa and sometimes an enlarged liver. Infected birds may not necessarily develop tumors, but they may lay fewer eggs.
Diffuse or nodular lymphoid tumors are common in the liver, spleen, and bursa, and are found occasionally in the kidneys, gonads, and mesentery. Involvement of the bursa has been considered virtually pathognomonic, although bursal lymphomas are now known to also be induced by reticuloendotheliosis virus. Sometimes the bursal tumors are small and observed only after careful examination of the mucosal surface of the organ. Usually, no enlargement of peripheral nerves is apparent, although such lesions have been noted after experimental inoculation of subgroup J virus. Microscopically, the tumor cells are uniform, large lymphocytes. Mitotic figures are frequent.
Diagnosis:Gross characteristics of diagnostic significance include the tumorous involvement of the liver, spleen, or bursa in the absence of peripheral nerve lesions. The tumors occur in birds >14 wk old. Histologically, the lymphoid cells are uniform in character, large, and contain IgM and B-cell markers on their surface. The tumor can be differentiated from those of Marek’s disease by gross and microscopic pathology and by molecular techniques that demonstrate the characteristic clonal integration of proviral DNA into the tumor cell genome with the associated disruption of the c-myc oncogene. Lymphoid leukosis cannot easily be differentiated from B-cell lymphomas caused by reticuloendotheliosis virus except by virological assays; however, such tumors probably are extremely rare in the field.
Control:Lymphoid leukosis appears to be controlled best by reduction and eventual eradication of the causative virus. Breeder flocks are evaluated for viral shedding by testing for viral antigens in the albumen of eggs with enzyme immunoassays or by biological assays for infectious virus. Eggs from shedder hens are discarded, so that progeny flocks typically have reduced levels of infection. If raised in small groups, infection-free flocks can be derived with relative ease. These control measures are applied only to primary breeder flocks. Voluntary programs to reduce viral infection have already reduced mortality from lymphoid leukosis and improved egg production in most layer strains; similar programs are underway in certain meat strains. Some breeders favor, and have virtually achieved, total eradication, while others favor a reduced level of viral infection. Some chickens have specific genetic resistance to infection with certain subgroups of virus. Although genetic cellular resistance will unlikely replace the need for reduction or eradication of the virus, the cellular receptor gene has recently been cloned, and quick molecular assays for viral susceptibility could be developed. Thus far, vaccination for tumor prevention has not been promising. However, strategies are under consideration to induce antibodies in breeders with recombinant vaccines lacking infectious avian leukosis virus to ensure protective maternal antibodies in progeny chicks.
Lymphoproliferative Disease in Turkeys