Etiology and Epidemiology:
FeLV is a retrovirus in the family Oncovirinae. Other oncoviruses
include feline sarcoma virus, mouse leukemia viruses, and 2 human
T-lymphotropic viruses. Although oncogenesis is one of their more
dramatic effects, oncoviruses cause many other diseases, including
degenerative, proliferative, and immunologic disorders.
There are 3 main FeLV subgroups of clinical importance. Subgroup A
viruses are found in all naturally infected cats. FeLV-A, the
original, archetypical form of the virus, is efficiently
transmitted among cats. FeLV-A viruses tend to be less pathogenic
than viruses of the other subgroups, but some strains cause severe
immunosuppression. Almost all naturally infected cats are
originally infected by FeLV-A. Within the infected cat, FeLV-A is
sometimes altered to produce FeLV-B and FeLV-C viruses. FeLV-B is
found in ~50% of naturally infected cats, along with FeLV-A. FeLV-A
and FeLV-B together are more frequently associated with neoplastic
diseases than is FeLV-A alone. FeLV-C viruses are isolated from
only 1% of naturally infected cats, along with FeLV-A and
sometimes both FeLV-A and FeLV-B. The presence of FeLV-C in an
infected cat is strongly associated with the development of
erythroid hypoplasia and consequent severe anemia. Viruses of all
3 subgroups are detected (but cannot be distinguished) by commonly
used FeLV diagnostic test kits.
The incidence of FeLV infection is directly related to the
population density of cats. Infection rates are highest in
catteries and multicat households, especially when cats have
access to the outdoors. In the USA, 1-2% of healthy stray urban
cats are persistently viremic. Not surprisingly, much higher
percentages of sick, “at risk” cats are found to be infected.
Persistently infected, healthy cats are the major reservoir of
FeLV. Carriers excrete large quantities of virus in saliva. Lesser
amounts of virus are excreted in tears, urine, and feces. Oronasal
contact with infectious saliva or urine is the most likely mode of
transmission. Nose-to-nose contact, mutual grooming, and shared
litter trays and food dishes facilitate transmission. Bite wounds
from infected cats are an efficient mode of transmission but occur
relatively infrequently in cats kept indoors 100% of the time.
Bites may be a more important mode of transmission in
Age resistance is significant. Young kittens are much more
susceptible than adults. The virus may be transmitted vertically
(in utero or by milk) or horizontally (by secretions and
excretions). Because FeLV is a fragile, enveloped virus and
because of age resistance, horizontal transmission between adults
usually requires prolonged, intimate contact. In addition, the
dose required for oronasal transmission of the virus is relatively
After oronasal inoculation, the virus first replicates in
oropharyngeal lymphoid tissue. From there, virus is carried in
blood mononuclear cells to spleen, lymph nodes, epithelial cells
of the intestine and bladder, salivary glands, and bone marrow.
Virus later appears in secretions and excretions of these tissues
and in peripheral blood leukocytes and platelets. Viremia is
usually evident 2-4 wk after infection. The acute stage of FeLV
infection (2-6 wk after infection) is rarely detected. It is
typically characterized by mild fever, malaise, lymphadenopathy,
and blood cytopenias.
In ~70% of adult cats, viremia and virus shedding are transient,
lasting only 1-16 wk. A few cats continue to shed virus in
secretions for several weeks to months after they cease to be
viremic. Virus may persist in bone marrow for a longer period, but
even this latent, or sequestered, infection usually disappears
within 6 mo. Some FeLV-exposed cats (~30%) do not mount an
adequate immune response and go on to become persistently (ie,
permanently) viremic. Persistently viremic cats develop fatal
diseases after a variable time period.
Disorders Caused by FeLV:
FeLV-related disorders are numerous and include immunosuppression,
neoplasia, anemia, immune-mediated diseases, reproductive
problems, and enteritis.
The immunosuppression caused
by FeLV is similar to that caused by feline immunodeficiency virus
Immunodeficiencies). There is an increased susceptibility
to bacterial, fungal, protozoal, and other viral infections.
Numbers of neutrophils and lymphocytes in the peripheral blood of
affected cats may be reduced, and those cells that are present may
be dysfunctional. Many FeLV-positive cats have low blood
concentrations of complement; this contributes to FeLV-associated
immunodeficiency and oncogenicity because complement is vital for
some forms of antibody-mediated tumor cell lysis. Much of the
immunodeficiency caused by FeLV is thought to be due to the high
degree of viral antigenemia.
Lymphoid or myeloid tumors (eg,
lymphoma, lymphoid leukemia, erythremic myelosis) develop in up to
30% of cats persistently infected with FeLV. Although FeLV-negative
(ie, nonviremic) cats also develop these tumors, they may still be
induced by FeLV, as many negative cats with lymphoma have viral
sequences that can be detected by immunohistochemistry and PCR.
Such cats may have been previously infected with FeLV despite
negative test results for the virus. The transient presence of
FeLV could have triggered lymphoma. However, the persistence of
FeLV antigen increases the risk of lymphoma by as much as 60-fold
compared with an FeLV-negative cat. Lymphoma is the most
frequently diagnosed malignancy of cats. Most American cats with
mediastinal, multicentric, or spinal forms of lymphoma are FeLV-positive.
However, in some parts of the world, these forms of lymphoma are
becoming much less common, and the proportion occurring in FeLV-positive
cats is decreasing. This may be related to effective control of
FeLV. Renal and GI forms of lymphoma are more likely to be found
in FeLV-negative cats.
Leukemia is a neoplastic proliferation of hematopoietic cells
originating in the bone marrow. The cell lines that become
neoplastic are neutrophils, basophils, eosinophils, monocytes,
lymphocytes, megakaryocytes, and erythrocytes. In cats, the
leukemias are strongly associated with FeLV infection and
sometimes (but not always) associated with neoplastic cells
circulating in the blood. Lymphoid leukemias are further divided
as acute and chronic. Acute lymphocytic leukemia is characterized
by lymphoblasts circulating in the blood. In chronic lymphocytic
leukemia, there is an increased number of circulating lymphocytes
that have normal morphology.
The anemia caused
by FeLV is usually nonregenerative and normochromic. There is
frequently an idiosyncratic macrocytosis. About 10% of FeLV-related
anemias are hemolytic and regenerative. This form of anemia may be
associated with hemobartonellosis or immune-mediated hemolysis, or
Immune complexes formed
in the presence of moderate antigen excess can cause systemic
vasculitis, glomerulonephritis, polyarthritis, and a variety of
other immune disorders. In FeLV-infected cats, immune complexes
form under conditions of antigen excess, because FeLV antigens are
abundant and anti-FeLV IgG antibodies are sparse. These conditions
are ideal for the development of immune-mediated disease.
Reproductive problems are
common; 68-73% of infertile queens have been reported to be FeLV-positive,
and 60% of queens that abort are FeLV-positive (although abortion
is a relatively uncommon cause of feline infertility). Fetal
death, resorption, and placental involution may occur in the
middle trimester of pregnancy, presumably as a result of in utero
infection of fetuses by virus transported across the placenta in
maternal leukocytes. Occasionally, infected queens give birth to
live, viremic kittens. Latently infected (ie, nonviremic) queens
may pass virus on to their kittens in milk.
Enteritis, resembling feline panleukopenia both clinically
and histopathologically, may develop. Clinical signs include
anorexia, depression, vomiting, and diarrhea (which may be
bloody). Because of the concurrent immunosuppression associated
with FeLV infection, septicemia may develop. Evidence suggests
that FeLV and feline panleukopenia virus may act synergistically
to produce this syndrome.
Other disorders may
also develop. FeLV occasionally causes a neuropathy leading to
anisocoria, urinary incontinence, or hindlimb paralysis. Certain
FeLV-induced lymphomas can produce identical clinical signs. If
antineoplastic therapy is planned, it is important to distinguish
neoplasia from neuropathy. FeLV can also cause quasineoplastic
disorders such as multiple cartilaginous exostoses (osteochondromatosis).
Two types of tests are readily available for clinical use. The
immunofluorescence assay (IFA) tests for the presence of FeLV
structural antigens (eg, p27 or other core antigens) in the
cytoplasm of cells suspected to be FeLV-infected. In clinical
practice, peripheral blood smears are usually used for the IFA,
but cytologic preparations of bone marrow or other tissues can
also be used. The IFA is considered to be the most reliable but
requires submission to a commercial laboratory, so results are
delayed. IFA-positive cats are considered to be persistently
viremic and have a poor longterm prognosis.
The more convenient ELISA can be performed in the veterinary
clinic and tests for the presence of soluble FeLV p27. FeLV
antigen may be present in the absence of intact, infectious viral
particles because excess FeLV antigens are released from infected
cells free of viral particles. The ELISA detects antigenemia
rather than viremia. Several different test kits are available;
most have sensitivities and specificities of 98%. Accuracy can be
improved by running both the IFA and ELISA on the same cat.
Diagnosis of FeLV-induced neoplasia is similar to that of other
tumors. Cytologic examination of fine-needle aspirates of masses,
lymph nodes, body cavity fluids (eg, pleural effusion), and
affected organs may reveal malignant lymphocytes. Bone marrow
examination may reveal leukemic involvement, even when the
peripheral blood appears normal. Biopsy and histopathologic
examination of abnormal tissues is often necessary for diagnostic
Ideally, an FeLV-infected cat would be identified early and
treated to eradicate the retroviral infection before FeLV-related
diseases had time to develop. Unfortunately, eradication of
retroviral infections at any stage of disease is extremely
difficult. Most infected cats are persistently viremic by the time
infection is diagnosed.
Many treatments have been administered in an attempt to reverse
viremia or decrease clinical signs associated with FeLV infection.
Anecdotal reports of antiviral agents and immunotherapeutic agents
reversing viremia, improving clinical signs, and prolonging
survival are abundant. Controlled studies using naturally infected
cats have been unable to substantiate a benefit from these
FeLV-positive cats can live without major diseases for several
years. Stress and sources of secondary infection should be
avoided. The cat should remain indoors 100% of the time to reduce
the risk of exposure to infectious agents and to prevent
transmission of the virus to other cats. Routine prophylactic care
for FeLV-infected cats is more important than for uninfected cats.
Routine vaccinations should be administered based on the risk to
the cat, with rabies vaccinations given to comply with local laws.
FeLV vaccinations should not be administered, as there is no
evidence to suggest a benefit. Physical examinations focusing on
external parasites, skin infections, dental disease, lymph node
size, and body weight should be performed every 6 mo.
Administration of an anthelmintic at these visits is recommended.
All infected cats should be neutered. Owners should be advised to
watch for signs of FeLV-related disease, particularly secondary
infections. Therapy for such infections or other illnesses should
be more aggressive and of longer duration, as the
immunocompromised condition renders the cat less able to fight
Feline lymphoma can be treated with cytotoxic drugs. These drugs
may cause significant toxicities if not dosed and administered
properly. (See alsoantineoplastic
Agents: Introduction .)
Most cytotoxic drugs are also carcinogens and must be handled
properly. Before undertaking treatment with these drugs,
veterinarians should familiarize themselves with proper dosing and
administration, appropriate monitoring of the patient, toxicities
and complications, and safe handling to prevent exposure of
veterinary personnel and owners to the agents and their
metabolites. Treated properly, most cats do not experience
significant toxicities and enjoy a good quality of life.
About 50% of cats with lymphoma that are treated will obtain a
complete remission (ie, no clinical evidence of disease). FeLV-negative
cats that attain a complete remission live an average of 9 mo, and
FeLV-positive cats have an average survival of 6 mo. Cats not
treated or those not responding to treatment survive ~6 wk.
Many protocols for treatment of feline lymphoma have been
published; most use similar drugs with differing schedules of
administration. One widely used protocol consists of an intensive
induction phase (vincristine 0.75 mg/m2, IV, weekly for
4 wk, cyclophosphamide 300 mg/m2, PO every 3 wk on the
same day as vincristine, and prednisone 10 mg/cat, PO, sid throughout
the protocol), followed by a less intensive maintenance phase (vincristine
and cyclophosphamide given every 3 wk on the same day, prednisone
continued daily). Treatment is continued for 1 yr or until
relapse. With this protocol, 79% of cats attained remission and
average survival was 150 days. Changing the maintenance protocol
to doxorubicin 25 mg/m2, IV, every 3 wk, provided an
average remission of 281 days. When relapse occurs, the drug
regimen can be changed and a second remission achieved; however,
second remissions seldom last as long as the first.
Acute lymphocytic leukemia is treated with the same protocol as
lymphoma, but only ~25% of cats obtain remission. For those that
obtain remission, the average length is 7 mo. Chronic lymphocytic
leukemia is best treated with chlorambucil (2 mg/cat, PO) and
prednisone (40 mg/m2, PO), given every other day on
alternating days. Leukemias other than lymphocytic are rarely
treated because the cats are extremely ill and very few respond to
Prevention and Control:
Testing should be mandatory in the following situations: 1) all
kittens at their first veterinary visit, so the owners can be
counseled regarding a cat that tests positive (as is routinely
done for congenital abnormalities), 2) all cats prior to entering
a household with existing uninfected cats, 3) all cats in an
existing household prior to admission of a new, uninfected cat,
and 4) all cats prior to their first FeLV vaccination.
FeLV vaccines are intended to protect cats against FeLV infection
or, at least, to prevent persistent viremia. Types of vaccines
include killed whole virus, subunit, and genetically engineered.
Vaccines may vary in protective effect, and manufacturers’ claims
and independent comparative studies should be carefully noted.
Vaccines are indicated only for uninfected cats; there is no
benefit in vaccinating an FeLV-positive cat. The cat’s risk, of
exposure to FeLV-positive cats should be assessed, and vaccines
used only for those cats at risk. Although the risk of tumor
development is low, FeLV vaccines have been associated with the
development of sarcomas at the vaccination site. Uninfected cats
in a household with infected cats should be vaccinated; however,
other means of protecting uninfected cats (eg, physical
separation) should also be used. Constant exposure to FeLV-infected
cats is likely to result in viral transmission regardless of
Some strains of FeLV can be grown in human tissue cultures. This
has led to concerns of possible transmission to humans. Several
studies have addressed this concern; none have shown any evidence
that any zoonotic risk exists.