AVIAN LEUCOSIS COMPLEX:

Introduction:
Under natural conditions, lymphoid leukosis has been the most common
form of the leukosis / sarcoma group of diseases seen in chicken flocks,
although recently myeloid leukosis has become prevalent.
Members of the leukosis / sarcoma group of avian retroviruses, including
avian leukosis viruses that were formerly placed in a subgenus termed
avian type C oncorna viruses have recently been termed alpha
retroviruses.
Members of this group of viruses have similar physical and molecular
characteristics and share a common group-specific antigen.
Avian 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 exist 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 avian leukosis tumors even in heavily infected flocks is
typically low (<4%), and disease is often inapparent.
Up to 1.5% excess mortality per wk has been reported in commercial
broiler- breeder flocks naturally infected with subgroup J avian leukosis
virus.

Etiology:
Avian leukosis is caused by certain members of the leukosis/sarcoma
group of avian retroviruses.
These viruses are commonly called avian leukosis viruses and belong to
subgroups A, B, C, D, E, and J.
Subgroups A and B have been most prevalent in western countries, until
the emergence of subgroup J.
Since the initial isolation of subgroup J virus in England, the virus has
been isolated from broiler-breeder stocks experiencing myeloid
neoplasms (myelocytoma) in many other countries.
Subgroup E avian leukosis viruses are endogenous viruses produced by
viral genes integrated into the host cell DNA and are only rarely
oncogenic.
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 avian leukosis virus are oncogenic, although some
differences in oncogenicity and replicative ability have been recognized.
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.
These tumors require 14-16 wk 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.
This enhancement requires 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 mortality from lymphoid leukosis.
Chickens with subclinical disease usually shed virus or viral antigen into
the albumen of eggs. The pathogenic mechanisms are poorly understood.
Myeloid leukosis is a malignancy of myeloid precursors arising from the
bone marrow. Its pathogenesis is not well understood.

Transmission and epidemiology:

Chickens are the natural hosts for all viruses of the leukosis/sarcoma
group; these viruses have not been isolated from other avian species
except pheasants, partridges, and quail.
Avian 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 viraemic 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 viraemia followed by
antibody production.
The earlier the infection, the more likely it is to lead to tolerance,
persistent viraemia, and tumors.
Other factors known to increase the susceptibility of chickens to
horizontal infection include the absence of maternal antibodies and the
presence of endogenous retroviruses, especially those associated with the
late 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.
The role of males in transmission of avian leukosis virus is uncertain.
Infected cocks apparently do not influence the rate of congenital
infection of progeny.
Cocks may act only as virus carriers and sources of contact or venereal
infection to other birds.
Chickens with lymphoid leukosis show nonspecific clinical
signs including inappetence, weakness, diarrhea, dehydration, and
emaciation.
Infected chickens 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.
Outbreaks of neoplasms other than lymphoid leukosis such as
myelocytomas, haemangiomas, and renal tumors have also been noted in
meat-type chickens infected with subgroup J avian leukosis virus.
Myelocytomatosis and skeletal myelocytomas may cause protuberances
on the head, thorax, and shanks.
Myelocytomas may develop in the orbit of the eye, causing hemorrhage
and blindness.
Haemangiomas may be seen in the skin, appearing as “blood blisters,”
which may rupture causing hemorrhage.
Renal tumors may cause paralysis due to pressure on the sciatic nerve.
Microscopically, especially in cases of myelocytomas induced by
subgroup J avian leukosis virus, the liver shows a massive intravascular
and extravascular accumulation of myelocytes characterized by the
presence of cytoplasmic eosinophilic granules.
Most strains of leukosis/sarcoma viruses also induce non lymphoid
tumors (including sarcomas), erythroblastosis, myeloblastosis,
myelocytomas, haemangiomas, nephroblastomas, osteopetrosis, and
related neoplasms.
The nature of the tumors and their frequency depend on virus and
chicken strain, age, dose, and route of infection.
Occasional outbreaks of predominantly one type of tumor are seen in the
field. The Rous sarcoma virus, a member of this group, has been widely
studied in the laboratory.
Each strain usually causes a predominantly neoplastic disease and can
be distinguished on the basis of pathogenicity.
Some viruses (eg, Rous sarcoma and erythroblastosis viruses) contain a
viral oncogene that leads to neoplasm induction within a short
incubation period, but such viruses are rare in the field.
Viruses with a viral oncogene are often defective for replication and
require the presence of a non defective helper virus to replicate.

DIAGONSIS:
 Because avian leukosis virus is widespread among chickens, virus
isolation and the demonstration of antigen or antibody have
limited or no value in diagnosing field cases of lymphomas.
 Gross characteristics of diagnostic significance include the
tumorous involvement of the liver, spleen, or bursa in the absence
of peripheral nerve lesions. Tumors occur in birds >14 wk old.
 In lymphoid leukosis, the lymphoid cells are histologically
uniform in character, large, and contain IgM and B-cell markers on
their surface.
 Tumors can be differentiated from those of Marek’s disease by
gross and microscopic pathology (although this can be difficult in
practice) 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
virologic assays; however, such tumors probably are extremely
rare.
 ELISA kits for detection of antibodies to avian leukosis virus
subgroups A, B, and J are available commercially.
CONTROLS:
 Because avian leukosis virus is widespread among chickens, virus
isolation and the demonstration of antigen or antibody have
limited or no value in diagnosing field cases of lymphomas.
 Gross characteristics of diagnostic significance include the
tumorous involvement of the liver, spleen, or bursa in the absence
of peripheral nerve lesions. Tumors occur in birds >14 wk old.
 In lymphoid leukosis, the lymphoid cells are histologically
uniform in character, large, and contain IgM and B-cell markers on
their surface.
 Tumors can be differentiated from those of Marek’s disease by
gross and microscopic pathology (although this can be difficult in
practice) 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
virologic assays; however, such tumors probably are extremely
rare.
 ELISA kits for detection of antibodies to avian leukosis virus
subgroups A, B, and J are available commercially.