**4. Feline leukemia virus**

364 Immunodeficiency

et al., 2011; O'Brien et al., 2012).

transmission of HIV occurs mainly via mucosal routes.

(Willet et al., 2006a; Grant et al., 2009; Elder et al., 2010).

**Table 3.** Comparative disease symptoms. Modified from Elder et al., 2010.

be higher in individuals with a strong THI-type response.

The similarities and discrepancies in the physiopathology of feline and human viruses in their respective natural hosts presents striking analogies, and several intriguing differences (Tables 3 and 4). FIV and HIV share a common pattern on clinical signs, having initially a nonspecific acute phase, followed by an asymptomatic phase and a phase in which the immune system is compromised and the animal is subjected to secondary infections (Sellon e Hartmann, 2006; Gunn-Moore & Reed, 2011; Hartmann, 1998; Hartamann, 2011; Magden

The dynamics of infection by FIV and HIV in their natural hosts are very similar, like HIV, FIV can be transmitted via mucosal exposure, blood transfer, and vertically via prenatal and postnatal routes, but FIV is principally transmitted through biting, while natural

The development of disease and clinical signs are also similar in human and cat (Fig. 1 and Table 3), both virus preferentially infects CD4 + T cells, while the cell surface receptors CD4 and CD134 are used for HIV and FIV, respectively, differ: the SU glycoprotein of FIV initially binds to CD134, triggering the conformational changes in SU that allow subsequent interaction between SU and the receptor CXCR4 (Grant et al., 2009). While some viruses arising in the later stages of HIV infections are able to use CXCR4, most natural isolates of HIV use a different chemokine receptor, CCR5. Nevertheless, since CCR5 and CD134 in humans and cats, respectively, are predominantly expressed on CD4+ T cells (Table 4)

Oral lesions Yes Yes Lymphadenopathy Yes Yes Neutropenia Yes Yes CD4 T cell depletion Yes Yes Hypergammaglobulinemia Yes Yes Wasting, diahrrea Yes Yes Secondary infections Yes Yes CNS lesions Yes Yes Neoplasia Yes Yes

Host immune response against FIV in domestic cats is very similar to those induced in HIVinfected patients. Both viruses cause dysfunction of the CD4+ lymphocyte early in infection, although FIV also infects the CD8+ subset, B lymphocytes and macrophages and ultimately cause immune system collapse. Epitopes recognized by humoral and cytotoxic cellular immune responses have been described in both *Env* and *Gag* genes. Some studies suggest that progression to AIDS may be associated with a TH2-type response, while resistance may

The evaluation of vaccine strategies in animal models is essential to instruct development of a vaccine against HIV. Currently, there are studies using transgenic cats expressing HIV

**FIV HIV** 

Feline leukemia virus has been reported mainly in domestic cats and, was first described in 1964 by William Jarret and co-workers. It is considered more pathogenic than FIV and FeLV infection has higher impact on mortality, because causes more severe immunosuppression than that caused by FIV infection (Hartmann, 2006; Lutz et al., 2009).

The FeLV genome contains envelope (*env)*, polymerase (*pol)* e group specific antigen (*gag)* genes that encode for the surface (SU) protein glycoprotein gp70 and the transmembrane (TM) protein p15E; reverse transcriptase, protease and integrase; internal virion proteins, including p15c, p12, p27 and p10; respectively. The p27, which is used for clinical detection of FeLV and gp70 defines the virus subgroup (Hartmann, 2006; Lutz et al., 2009).

Although it has not been described serotypes for FeLV virus isolates have variants or subgroups (FeLV-A, FeLV-B, FeLV-C and FeLV-T). These subgroups are distinguished by the nucleotide sequence of the *env* gene and, antigenically they are closely related. Variations in protein SU sequences would be responsible for use by the virus of different cell receptors, resulting in differences in tropism including bone marrow, salivary glands and respiratory epithelium, and pathogenicity of field isolates (Neil et al., 1991; Roy-Burman et al., 1995). Subtype A is more disseminated, it is involved in all clinical infections and is related to immunodeficiency. Only FeLV A is contagious and passed horizontally from cat to cat in nature. The host cell receptor used by FeLV is *Feline highaffinity thiamine transporter 1* (feTHTR1), found in absorption tissues and small intestine besides liver and kidneys, and also in cells of the lymphoid system. This wide distribution is consistent with the fact that the FeLV-A is found in a variety of tissues and cells and this subgroup can cause lymphomas, but usually causes injury moderate in the absence of other subgroups. Subtype B originates from recombination of FeLV-A is primarily associated with tumors. Subtype C considered the most pathogenic subgroup, emerges from mutations in the *env* gene of subtype A and is mainly associated with non-regenerative anemia*.* Subtype T was originally isolated from a cat with FeLV induced immunodeficiency (FAIDS). This subgroup arises from mutations in the SU gene sequence of the FeLV-A with approximately 96% similarity. It is defined by its T lymphotropism. This subgroup requires a membrane-spanning receptor molecule (PIT1) and a co-receptor protein (FeLIX) to infect T lymphocytes and causes usually severe immunosuppression. In fact, all naturally infected cats carry FeLV A either alone or in combination with FeLV B, FeLV C, or both (Neil et al., 1991; Roy-Burman et al., 1995; Hartamann, 2006; Lutz et al., 2009).

Feline Immunodeficiency 367

**Healthy cat** 

Animal resistant future infections for a period of time

(complete elimation) FeLV positive (continued viremia)

Days FeLV negative -

3 weeks FeLV positive

3-13 weeks FeLV negative

3-13 weeks FeLV positve

will be infected for the remainder of their lives. The pathogenesis of FeLV is different in each cat and depends on immune status and age, but can be classified into six stages (Table 6) (Hard et al., 1976; Charreyre & Pedersen, 1991; Hartmann, 2006; Fugino et al., 2008; Lutz,

> Efficient - virus neutralization

Failure to develop an immune response effective

Body inactive the virus, but not neutralizes

sequestered in the epithelial tissue, replicates itself, but leaves the cells

Clinical signs associated with FeLV infection are variable (Fig. 4). It has seen tumors in infected cats once FeLV is a major oncogene that causes different kind of tumors, most commonly malignant lymphoma and leukemia and other hematopoietic tumors. It also induces thymic atrophy and depletion of lymph node paracortical zones following infection Besides that it has been found immunosuppression with poor response to T-cell mitogens, reduced immunoglobulin production; hematologic disorders like lymphopenia and neutropenia; immune-mediated diseases; neuropathy; reproductive disorders; fading kitten syndrome and opportunistic infections. The lymphopenia may be characterized by preferential loss of CD4+/CD8+ ratio and losses of helper cells and cytotoxic supressor cells and primary and secondary humoral antibody responses are delayed and decreased

FeLV infected cats having concurrent protozoal, bacterial, viral, and fungal infections, most commonly bartonellosis, respiratory infections and coccidiosis (Wolf-Jäckel et al., 2012; Sobrinho et al., 2012). Diseases such as hemolytic anemia, glomerulonephritis, chronic enteritis with intestinal epithelial cell degeneration and necrosis of the crypts, liver disease, reabsorption fetal, abortion, stillbirth, lymphadenopathy, polyarthritis and neurological

**Response immune Days after** 

**infection** 

2009).

**Classification of evolution of the disease** 

Regressive infection extinct

Progressive Persistent

Regressive Latent

**Classification of infected animals** 

> Transient viremia

viremia

infection

(Hartmann, 2006; Lutz et al., 2009; Hartmann, 2011).

Atypical Complete virus is

**Table 5.** Immune responses following infection. Modified from Hartmann, 2006.

#### **4.1. Epidemiology and transmission**

The feline leukemia virus has a worldwide distribution. FeLV is contagious and spreads through close contact between viral shedding, but the prevalence of infection varies greatly depending on their age, health, environment, density of animals and lifestyle (Hard et al., 1976; Grant et al., 1980). The kittens are more susceptible, since the resistance develops with age. Because of advances in the diagnosis of disease and vaccination the prevalence of FeLV has dropped substantially in the last two decades. In Shelters and places where there is a high density of animals, it is advisable to proceed diagnosis of all animals. Infected animals should be euthanized or isolated from not infected animals.

FeLV is transmitted mainly by oronasal contact, through saliva, urine, feces, ingestion of contaminated food and water and also through bites. Transmission can also take place from an infected mother cat to her kittens, either before they are born or while they are nursing. Older cats are more resistant to FeLV infection, but can be infected by high viral doses (Lutz et al., 2009).

#### **4.2. Pathogenesis, immunity and clinical symptoms**

FeLV is present in the blood during two different stages of infection: primary viremia, an early stage of virus infection. During early stage some cats are able to mount an effective immune response, eliminate the virus from the bloodstream. The second stage is characterized by persistent infection of the bone marrow and other tissues (Table 5) (Hard et al., 1976; Hartmann, 2006; Fugino et al., 2008). If FeLV infection progresses to this stage it has passed a point of no return: the overwhelming majority of cats with secondary viremia will be infected for the remainder of their lives. The pathogenesis of FeLV is different in each cat and depends on immune status and age, but can be classified into six stages (Table 6) (Hard et al., 1976; Charreyre & Pedersen, 1991; Hartmann, 2006; Fugino et al., 2008; Lutz, 2009).

366 Immunodeficiency

et al., 2009).

1995; Hartamann, 2006; Lutz et al., 2009).

**4.1. Epidemiology and transmission** 

should be euthanized or isolated from not infected animals.

**4.2. Pathogenesis, immunity and clinical symptoms** 

al., 1995). Subtype A is more disseminated, it is involved in all clinical infections and is related to immunodeficiency. Only FeLV A is contagious and passed horizontally from cat to cat in nature. The host cell receptor used by FeLV is *Feline highaffinity thiamine transporter 1* (feTHTR1), found in absorption tissues and small intestine besides liver and kidneys, and also in cells of the lymphoid system. This wide distribution is consistent with the fact that the FeLV-A is found in a variety of tissues and cells and this subgroup can cause lymphomas, but usually causes injury moderate in the absence of other subgroups. Subtype B originates from recombination of FeLV-A is primarily associated with tumors. Subtype C considered the most pathogenic subgroup, emerges from mutations in the *env* gene of subtype A and is mainly associated with non-regenerative anemia*.* Subtype T was originally isolated from a cat with FeLV induced immunodeficiency (FAIDS). This subgroup arises from mutations in the SU gene sequence of the FeLV-A with approximately 96% similarity. It is defined by its T lymphotropism. This subgroup requires a membrane-spanning receptor molecule (PIT1) and a co-receptor protein (FeLIX) to infect T lymphocytes and causes usually severe immunosuppression. In fact, all naturally infected cats carry FeLV A either alone or in combination with FeLV B, FeLV C, or both (Neil et al., 1991; Roy-Burman et al.,

The feline leukemia virus has a worldwide distribution. FeLV is contagious and spreads through close contact between viral shedding, but the prevalence of infection varies greatly depending on their age, health, environment, density of animals and lifestyle (Hard et al., 1976; Grant et al., 1980). The kittens are more susceptible, since the resistance develops with age. Because of advances in the diagnosis of disease and vaccination the prevalence of FeLV has dropped substantially in the last two decades. In Shelters and places where there is a high density of animals, it is advisable to proceed diagnosis of all animals. Infected animals

FeLV is transmitted mainly by oronasal contact, through saliva, urine, feces, ingestion of contaminated food and water and also through bites. Transmission can also take place from an infected mother cat to her kittens, either before they are born or while they are nursing. Older cats are more resistant to FeLV infection, but can be infected by high viral doses (Lutz

FeLV is present in the blood during two different stages of infection: primary viremia, an early stage of virus infection. During early stage some cats are able to mount an effective immune response, eliminate the virus from the bloodstream. The second stage is characterized by persistent infection of the bone marrow and other tissues (Table 5) (Hard et al., 1976; Hartmann, 2006; Fugino et al., 2008). If FeLV infection progresses to this stage it has passed a point of no return: the overwhelming majority of cats with secondary viremia


**Table 5.** Immune responses following infection. Modified from Hartmann, 2006.

Clinical signs associated with FeLV infection are variable (Fig. 4). It has seen tumors in infected cats once FeLV is a major oncogene that causes different kind of tumors, most commonly malignant lymphoma and leukemia and other hematopoietic tumors. It also induces thymic atrophy and depletion of lymph node paracortical zones following infection Besides that it has been found immunosuppression with poor response to T-cell mitogens, reduced immunoglobulin production; hematologic disorders like lymphopenia and neutropenia; immune-mediated diseases; neuropathy; reproductive disorders; fading kitten syndrome and opportunistic infections. The lymphopenia may be characterized by preferential loss of CD4+/CD8+ ratio and losses of helper cells and cytotoxic supressor cells and primary and secondary humoral antibody responses are delayed and decreased (Hartmann, 2006; Lutz et al., 2009; Hartmann, 2011).

FeLV infected cats having concurrent protozoal, bacterial, viral, and fungal infections, most commonly bartonellosis, respiratory infections and coccidiosis (Wolf-Jäckel et al., 2012; Sobrinho et al., 2012). Diseases such as hemolytic anemia, glomerulonephritis, chronic enteritis with intestinal epithelial cell degeneration and necrosis of the crypts, liver disease, reabsorption fetal, abortion, stillbirth, lymphadenopathy, polyarthritis and neurological

diseases such as peripheral neuropathies, may be related to FeLV infection (Hartmann, 2006; Lutz et al., 2009; Hartmann, 2011).

Feline Immunodeficiency 369

**4.3. Diagnosis and management of FeLV-infected cats** 

naturally and may react negatively with a specific PCR.

(Gomes-Keller et al., 2006; Hartmann, 2006; Lutz et al., 2009).

weeks.

disinfectant.

The correct and early diagnosis is important for prevention and control of FeLV infection Diagnostic tests detect antigens and, cats of any age should be tested. For the diagnosis of FeLV, virus isolation is not widely used, because it is difficult, time consuming to perform and requires special facilities, though viral antigens could be detected in peripheral blood cells, this method has been considered as the ultimate diagnostic criterion. Most often, the diagnosis of infection is done based on clinical history and detection of antigens, the FeLV core protein (p27), in leukocytes, plasma, serum or saliva of suspected animals (Barr, 1998; Hartmann, 2006). The direct immunofluorescence assay in blood smears, is the most commonly used diagnostic methods for detection of the virus, targeting mainly proteins p27 and p55 that are present in infected leukocytes (Hard, 1991). Tests such as ELISA and immunochromatography for the p27 protein have high sensitivity and specificity and are preferred used because they are less laborious, however, when doubtful results occurs it should be confirmed by direct immunofluorescence (Table 7) (Hard, 1991, Hartmann et al., 2007; Lutz et al., 2009). PCR is being used currently for detection of viral nucleic acid (RNA or proviral DNA) and is highly strain specific. PCR positive for FeLV proviral DNA indicates the presence of exogenous but not necessarily can be used as a diagnosis for viremia (Gomes-Keller et al., 2006). In these cases the RT-PCR detects the presence of viral RNA and informs the development of viremia in infected animals, but current reagents and testing protocols should be well standardized. As a retrovirus, mutations in FeLV occur

It is necessary a good classification of the stage (Table 6) of the disease to obtain an accurate diagnosis. In phases I-III only ELISA can detect viral antigens for FeLV, and in the stages IV-VI can be detected by ELISA, immunofluorescence and PCR. The combination of testing determines the FeLV infection status of most cats. Recommend annual retesting after any discordant test result until agreement. A positive test doubtful a healthy animal, it should be done further confirmatory tests such as direct immunofluorescence and PCR for provirus

For an accurate diagnosis, it is also necessary to evaluate the age and lifestyle of the animal (Table 7): Negative animals under 12 weeks who had contact with sick birds or other animals should be retested within 4-6 weeks; positive results indicate that at this age the animals are infected. Negative animals with more than 12 weeks who had contact with sick birds or other animals should be retested within 6-8 weeks; positive results at this age should be classified as follows: sick animals (positive), healthy animals, retesting within 6-8

The early and precise diagnosis is needed to enable rapid intervention. FeLV-infected cats should be isolated from uninfected ones. It is also recemmented that they could be examined by the vet regularly (every 6 months), doing biochemical tests, complete blood count and urinalysis. Infected animals should be sterilized to minimize the transmission. The living environment should be cleaned periodically, because FeLV is sensitive to any type of


**Table 6.** Stages of replication of the virus of feline leukemia (FeLV).

**Figure 4.** Gingivitis. (Courtesy Marcia Moller Nogueira).

The feline oncovirus associated-membrane antigens (FOCMA) may be associated with immunodeficiency that occurs because of depletion of lymphoid cells infected, probably due to antibody-mediated cytotoxic. Leukemia and anemia are induced by the transformation of stem cells, myeloid and lymphoid lineages, induced by infection with FeLV (Hard et al., 1976; Lutz et al., 2009; Hartmann, 2011).

#### **4.3. Diagnosis and management of FeLV-infected cats**

368 Immunodeficiency

Lutz et al., 2009; Hartmann, 2011).

I Oropharynx and

II Lymphocytes and

III Systemic lymphoid

IV Bone marrow cells

V Bone marrow stem

VI Viremia medullary

**Figure 4.** Gingivitis. (Courtesy Marcia Moller Nogueira).

1976; Lutz et al., 2009; Hartmann, 2011).

The feline oncovirus associated-membrane antigens (FOCMA) may be associated with immunodeficiency that occurs because of depletion of lymphoid cells infected, probably due to antibody-mediated cytotoxic. Leukemia and anemia are induced by the transformation of stem cells, myeloid and lymphoid lineages, induced by infection with FeLV (Hard et al.,

lymph nodes

monocytes

centers

and epithelial cell

cells

epithelial and lymphoid

**Table 6.** Stages of replication of the virus of feline leukemia (FeLV).

diseases such as peripheral neuropathies, may be related to FeLV infection (Hartmann, 2006;

Stages Replication region Pathogenesis Days post

Infects lymphocytes, which travel to the bone marrow

Immune suppression, thymic atrophy, lymphopenia, neutropenia, neutrophil function abnormalities, loss of CD4+ cells and CD8+ lymphocytes

> Myelossuppression and leukemia

> Thrombocytopenia and neutropenia

Immune suppression 2- 12 days

Anaemia and lymphoma 2- 6 weeks

infection

2- 12 days

2- 12 days

4- 6 weeks

4- 6 weeks

The correct and early diagnosis is important for prevention and control of FeLV infection Diagnostic tests detect antigens and, cats of any age should be tested. For the diagnosis of FeLV, virus isolation is not widely used, because it is difficult, time consuming to perform and requires special facilities, though viral antigens could be detected in peripheral blood cells, this method has been considered as the ultimate diagnostic criterion. Most often, the diagnosis of infection is done based on clinical history and detection of antigens, the FeLV core protein (p27), in leukocytes, plasma, serum or saliva of suspected animals (Barr, 1998; Hartmann, 2006). The direct immunofluorescence assay in blood smears, is the most commonly used diagnostic methods for detection of the virus, targeting mainly proteins p27 and p55 that are present in infected leukocytes (Hard, 1991). Tests such as ELISA and immunochromatography for the p27 protein have high sensitivity and specificity and are preferred used because they are less laborious, however, when doubtful results occurs it should be confirmed by direct immunofluorescence (Table 7) (Hard, 1991, Hartmann et al., 2007; Lutz et al., 2009). PCR is being used currently for detection of viral nucleic acid (RNA or proviral DNA) and is highly strain specific. PCR positive for FeLV proviral DNA indicates the presence of exogenous but not necessarily can be used as a diagnosis for viremia (Gomes-Keller et al., 2006). In these cases the RT-PCR detects the presence of viral RNA and informs the development of viremia in infected animals, but current reagents and testing protocols should be well standardized. As a retrovirus, mutations in FeLV occur naturally and may react negatively with a specific PCR.

It is necessary a good classification of the stage (Table 6) of the disease to obtain an accurate diagnosis. In phases I-III only ELISA can detect viral antigens for FeLV, and in the stages IV-VI can be detected by ELISA, immunofluorescence and PCR. The combination of testing determines the FeLV infection status of most cats. Recommend annual retesting after any discordant test result until agreement. A positive test doubtful a healthy animal, it should be done further confirmatory tests such as direct immunofluorescence and PCR for provirus (Gomes-Keller et al., 2006; Hartmann, 2006; Lutz et al., 2009).

For an accurate diagnosis, it is also necessary to evaluate the age and lifestyle of the animal (Table 7): Negative animals under 12 weeks who had contact with sick birds or other animals should be retested within 4-6 weeks; positive results indicate that at this age the animals are infected. Negative animals with more than 12 weeks who had contact with sick birds or other animals should be retested within 6-8 weeks; positive results at this age should be classified as follows: sick animals (positive), healthy animals, retesting within 6-8 weeks.

The early and precise diagnosis is needed to enable rapid intervention. FeLV-infected cats should be isolated from uninfected ones. It is also recemmented that they could be examined by the vet regularly (every 6 months), doing biochemical tests, complete blood count and urinalysis. Infected animals should be sterilized to minimize the transmission. The living environment should be cleaned periodically, because FeLV is sensitive to any type of disinfectant.


Feline Immunodeficiency 371

and can be vaccinated at intervals of 2-3 years. Vaccines prepared with inactivated whole virus obtained from cell cultures are available commercially, as well as vaccines containing recombinant viral proteins expressed in heterologous systems. No FeLV vaccine provides 100% efficacy of protection for FeLV and none prevents infection, but vaccination offers good prevention of fatal cases. The immunization of animals with inactivated vaccines may result in a reduction of 70% incidence of the disease. FeLV immunization should be part of the routine vaccination programmed for pet cats. However, the most effective way to prevent the spread of infection is testing for FeLV and preventing exposure of healthy cats

to FeLV infected cats (Cotter, 1991; McCaw, 1995, Hartmann, 2006; Lutz et al., 2009).

Charreyre, C., Pedersen, N. C. (1991). Study of feline leukemia virus immunity. *J. Am. Vet.* 

Cotter, S. M. (1991). Management of healthy feline leukemia virus-positive cats. *J. Am. Vet.* 

Courchamp, F., Pontier, D. (1994). Feline immunodeficiency virus: an epidemiological

de Parseval, A., Chatterji, U., Morris, G., Sun, P., Olson, A. J. & Elder, J. H. (2005). Structural mapping of CD134 residues critical for interaction with feline immunodeficiency virus.

Doménech, A., Miró, G., Collado, V. M., Ballesteros, N., Sanjosé, L., Escolar, E., Martin, S. & Gomez-Lucia E. (2011). Use of recombinant interferon omega in feline retrovirosis: from

Elder, J. H., Sundstrom, M., de Rozieres, S., de Parseval A., Grant, C. K., Lin Y. C. (2008). Molecular mechanisms of FIV infection. *Vet. Immunol. Immunopathol*. 15;123(1-2):3-13. Elder, J. H., Lin, Y. C., Fink, E. & Grant, C. K. (2010). Feline immunodeficiency virus (FIV) as a model for study of lentivirus infections: parallels with HIV. *Curr.* HIV *Res.* 8(1):73-80. Fujino, Y., Ohno, K., Tsujimoto, H. (2008). Molecular pathogenesis of feline leukemia virusinduced malignancies: insertional mutagenesis. *Vet. Immunol. Immunopathol.* 123(1-

Gomes-Keller, M. A., Gönczi, E., Tandon, R., Riondato, F., Hofmann-Lehmann, R., Meli, M. L., Lutz, H. (2006). Detection of feline leukemia virus RNA in saliva from naturally infected cats and correlation of PCR results with those of current diagnostic methods. *J.* 

Grant, C. K., Essex, M., Gardner, M. B., Hardy, W. D. Jr. (1980). Natural feline leukemia virus infection and the immune response of cats of different ages. *Cancer Res.* 40(3):823-9.

Fabiana Alves and Jenner Karlisson Pimenta dos Reis

review. *C. R. Acad. Sci. III.* 317(12):1123-34.

Barr, F. (1998). Feline Leukemia Virus. *J. Small Anim. Pract.* 39(1):41-43.

theory to practice. *Vet. Immunol. Immunopathol.* 143(3-4):301-6.

*Universidade Federal de Minas Gerais, Brazil* 

*Med. Assoc.* 199(10):1316-24.

*Med. Assoc.* 199(10):1470-3.

*Nat. Struct. Mol. Biol*. 12(1):60-6.

*Clin. Microbiol.* 44(3):916-22.

**Author details** 

**5. References** 

2):138-43.

**Table 7.** Interpretation of results obtained by ELISA and direct immunofluorescence. Modified from Hartmann, 2006.

As immunomodulatory therapy are used to good clinical improvement, but are still under study. Antivirals such as AZT that acts effectively against FeLV replication in vitro and in vivo reducing the viral load, improving the immune response and clinical condition of the animal (Cotter, 1991; Hartmann, 2006; Lutz et al., 2009). Infected animals should be treated for other infections promptly to prevent an impaired immune system and should be vaccinated regularly against other pathogens like rabies virus, feline panleukopenia, rhinotracheitis, calicevirose, chlamydiosis and other (Cotter, 1991; McCaw, 1995, Lutz et al., 2009). Corticosteroids should be avoided, but if stomatitis or gingivitis occurs they can be used to facilitate the intake of food. In cats with anemia, blood transfusions may be useful and leukopenia can be treated with colony-stimulating factors (Cotter, 1991; McCaw, 1995, Lutz et al., 2009).

All animals should be tested for FeLV and thereafter be vaccinated at the age of 8-9 weeks and again at 12 weeks with annual boosters. Older animals are less susceptible to infection and can be vaccinated at intervals of 2-3 years. Vaccines prepared with inactivated whole virus obtained from cell cultures are available commercially, as well as vaccines containing recombinant viral proteins expressed in heterologous systems. No FeLV vaccine provides 100% efficacy of protection for FeLV and none prevents infection, but vaccination offers good prevention of fatal cases. The immunization of animals with inactivated vaccines may result in a reduction of 70% incidence of the disease. FeLV immunization should be part of the routine vaccination programmed for pet cats. However, the most effective way to prevent the spread of infection is testing for FeLV and preventing exposure of healthy cats to FeLV infected cats (Cotter, 1991; McCaw, 1995, Hartmann, 2006; Lutz et al., 2009).

#### **Author details**

370 Immunodeficiency

Less than 12 weeks

More than 12 weeks

Hartmann, 2006.

Lutz et al., 2009).

**Age Result of the** 

**diagnosis**

Negative

Positive

Negative

Positive

**Lifestyle of the animal** 

Kept contact with other animals and /or sick animals

Not kept contact with other animals and / or sick animals

Even that has ingested colostrum positive for FeLV

Animal exposed to sick or diseased animals

Animal no manifestations

**Table 7.** Interpretation of results obtained by ELISA and direct immunofluorescence. Modified from

As immunomodulatory therapy are used to good clinical improvement, but are still under study. Antivirals such as AZT that acts effectively against FeLV replication in vitro and in vivo reducing the viral load, improving the immune response and clinical condition of the animal (Cotter, 1991; Hartmann, 2006; Lutz et al., 2009). Infected animals should be treated for other infections promptly to prevent an impaired immune system and should be vaccinated regularly against other pathogens like rabies virus, feline panleukopenia, rhinotracheitis, calicevirose, chlamydiosis and other (Cotter, 1991; McCaw, 1995, Lutz et al., 2009). Corticosteroids should be avoided, but if stomatitis or gingivitis occurs they can be used to facilitate the intake of food. In cats with anemia, blood transfusions may be useful and leukopenia can be treated with colony-stimulating factors (Cotter, 1991; McCaw, 1995,

All animals should be tested for FeLV and thereafter be vaccinated at the age of 8-9 weeks and again at 12 weeks with annual boosters. Older animals are less susceptible to infection

Sick animal Infected

Animal health Re-test after 6-8

**Interpretation Measure** 

Infected Isolation of

The result of the last test will be conclusive

animal and clinical control every six months.

The result of the last test will be conclusive

The result of the last test will be conclusive

Re-test after 4-6 weeks

Uninfected

Re-test after 6-8 weeks

Uninfected

weeks

Fabiana Alves and Jenner Karlisson Pimenta dos Reis *Universidade Federal de Minas Gerais, Brazil* 

#### **5. References**

Barr, F. (1998). Feline Leukemia Virus. *J. Small Anim. Pract.* 39(1):41-43.


Grant, C. K., Fink, E. A., Sundstrom, M., Torbett, B. E., Elder, J. H. (2009). Improved health and survival of FIV-infected cats is associated with the presence of autoantibodies to the primary receptor, CD134. *Proc. Natl. Acad. Sci. U S A*. 24;106(47):19980-5.

Feline Immunodeficiency 373

Magden, E., Quackenbush, S. L. & VandeWoude, S. (2011). FIV associated neoplasms--a

McCaw D. (1995). Caring for the retrovirus infected cat. *Semin. Vet. Med. Surg. (Small Anim.)*.

McDonnel, S. J., Sparger, E. E., Luciw, P. A., Murphy, B. G. (2012). Transcriptional Regulation of Latent Feline Immunodeficiency Virus in Peripheral CD4+ T-

Medeiros, S. O., Martins, A. N., Dias, C. G., Tanuri, A., Brindeiro, R.D. (2012). Natural transmission of feline immunodeficiency virus from infected queen to kitten. *Virol. J.*

Mohammadi, H., Bienzle, D. (2012). Pharmacological Inhibition of Feline Immunodeficiency

Neil, J. C., Fulton, R., Rigby, M., Stewart, M. (1991). Feline leukaemia virus: generation of

O'Brien, S. J., Troyer, J. L., Brown, M. A., Johnson, W. E., Antunes, A., Roelke, M. E., Pecon-Slattery, J. (2012). Emerging viruses in the Felidae: shifting paradigms. *Viruses.* 4(2):236-

Olmsted, R. A., Hirsch, V. M., Purcell, R. H., Johnson, P. R. (1989). Nucleotide sequence analysis of feline immunodeficiency virus: genome organization and relationship to

Pedersen, N. C., Ho, E.W., Brown, M. L., Yamamoto, J. K. (1987). Isolation of a Tlymphotropic virus from domestic cats with an immunodeficiency-like syndrome.

Roy-Burman, P. (1995). Endogenous env elements: partners in generation of pathogenic

Savarino, A., Pistello, M., D'Ostilio, D., Zabogli, E., Taglia, F., Mancini, F., Ferro, S., Matteucci, D., De Luca, L., Barreca, M. L., Ciervo, A., Chimirri, A., Ciccozzi, M., Bendinelli, M. (2007). Human immunodeficiency virus integrase inhibitors efficiently suppress feline immunodeficiency virus replication *in vitro* and provide a rationale to

Sellon, R. K. & Hartmann, K. (2006). Feline Immunodeficiency Virus infection. Greene, C. E.

Simões, R. D., Howard, K. E., Dean, G. A. (2012). In Vivo Assessment of Natural Killer Cell Responses during Chronic Feline Immunodeficiency Virus Infection. *PLoS One.*

Sobrinho, L. S., Rossi, C. N., Vides, J. P., Braga, E.T., Gomes, A. A., de Lima, V. M., Perri, S. H., Generoso, D., Langoni, H., Leutenegger, C., Biondo, A. W., Laurenti, M. D. & Marcondes, M. (2012). Coinfection of Leishmania chagasi with Toxoplasma gondii, Feline Immunodeficiency Virus (FIV) and Feline Leukemia Virus (FeLV) in cats from an

Sodora, D. L., Shpaer, E. G., Kitchell, B. E., Dow, S. W., Hoover, E. A., Mullins, J. I. (1994). Identification of three feline immunodeficiency virus (FIV) env gene subtypes and

redesign antiretroviral treatment for feline AIDS. *Retrovirology*. 30;4:79.

endemic area of zoonotic visceral leishmaniasis. *Vet Parasitol*, *in press*.

In: *Infectious diseases of the dog and cat*. 3ª ed. Elsevier, p. 131-142.

pathogenic and oncogenic variants. *Curr. Top. Microbiol. Immunol*. 171:67-93.

mini-review. *Vet. Immunol. Immunopathol.* 143(3-4):227-34.

Virus (FIV). *Viruses*. 4(5):708-24. Epub 2012 Apr 27.

other lentiviruses. *Proc. Natl. Acad. Sci. U S A*. 86(20):8088-92.

feline leukemia viruses. *Virus Genes*. 11(2-3):147-61.

10(4):216-219.

25;9(1):99.

57.

*Science*. 235(4790):790-3.

7(5):e37606.

lymphocytes. *Viruses*. 4(5):878-88.


Magden, E., Quackenbush, S. L. & VandeWoude, S. (2011). FIV associated neoplasms--a mini-review. *Vet. Immunol. Immunopathol.* 143(3-4):227-34.

372 Immunodeficiency

Grant, C. K., Fink, E. A., Sundstrom, M., Torbett, B. E., Elder, J. H. (2009). Improved health and survival of FIV-infected cats is associated with the presence of autoantibodies to the

Gunn-Moore, D. A. & Reed, N. (2011). CNS disease in the cat: Current knowledge of

Hardy, W. D. Jr., Hess, P. W., MacEwen, E. G., McClelland, A. J., Zuckerman, E. E., Essex, M., Cotter, S. M., Jarrett, O. (1976). Biology of feline leukemia virus in the natural

Hardy, W. D. Jr. (1991). General principles of retrovirus immunodetection tests. *J. Am. Vet.* 

Hartmann, K. (1998). Feline immunodeficiency virus infection: an overview. *Vet. J.* 

Hartmann, K. (2006). Feline Leukemia Virus infection. Greene, C. E. In: *Infectious diseases of* 

Hartmann, K. (2011). Clinical aspects of feline immunodeficiency and feline leukemia virus

Hartmann, K., Griessmayr, P., Schulz, B., Greene, C. E., Vidyashankar, A. N., Jarrett, O. & Egberink, H. F. (2007). Quality of different in-clinic test systems for feline immunodeficiency virus and feline leukaemia virus infection. *J. Fel. Med. Surg.*, v. 9, n.

Hosie, M. J. & Jarrett, O. (1990). Serological responses of cats to feline immunodeficiency

Hosie, M. J., Addie, D., Belák, S., Boucraut-Baralon, C., Egberink, H., Frymus, T., Gruffydd-Jones, T., Hartmann, K., Lloret, A., Lutz, H., Marsilio, F., Pennisi, M. G., Radford, A. D., Thiry, E., Truyen, U. & Horzinek, M. C. (2009). Feline immunodeficiency. ABCD

Kenyon, J. C., Lever, A.M. (2011). The molecular biology of feline immunodeficiency virus

Klonjkowski, B., Klein, D., Galea, S., Gavard, F., Monteil, M., Duarte, L., Fournier, A., Sayon, S., Górna, K., Ertl, R., Cordonnier, N., Sonigo, P., Eloit, M., Richardson, J. (2009). Gagspecific immune enhancement of lentiviral infection after vaccination with an

Korman, R. M., Cerón, J. J., Knowles, T. G., Barke,r E. N., Eckersall, P. D., Tasker, S. (2012). Acute phase response to Mycoplasma haemofelis and 'Candidatus Mycoplasma haemominutum' infection in FIV-infected and non-FIV-infected cats. *Vet. J. in press.* Kurosawa, K., Ikeda, Y., Miyazawa, T., Izumiya, Y., Nishimura, Y., Nakamura, K., Sato, E., Mikami, T., Kai, C., Takahashi, E. (1999). Development of restriction fragment-length polymorphism method to differentiate five subtypes of feline immunodeficiency virus.

Lutz, H., Addie, D., Belák, S., Boucraut-Baralon, C., Egberink, H., Frymus, T., Gruffydd-Jones, T., Hartmann, K., Hosie, M. J., Lloret, A., Marsilio, F., Pennisi, M. G., Radford, A. D., Thiry, E., Truyen, U. & Horzinek, M. C. (2009). Feline leukaemia. ABCD guidelines

guidelines on prevention and management. *J.* Feline *Med. Surg.* 11(7):575-84.

adenoviral vector in an animal model of AIDS. *Vaccine*. 5;27(6):928-39.

on prevention and management. *J.* Feline *Med. Surg.* 11(7):565-74.

primary receptor, CD134. *Proc. Natl. Acad. Sci. U S A*. 24;106(47):19980-5.

infectious causes. *J. Feline Med. Surg.* 13(11):824-36.

environment. *Cancer Res.* 36(2 pt 2):582-8.

*the dog and cat*. 3ª ed. Elsevier, p. 105-131.

infection. *Vet. Immunol. Immunopathol*. 143(3-4):190-201.

*Med. Assoc.* 199(10):1282-7.

155(2):123-37.

6, p. 439-45.

virus. *AIDS*. 4(3):215-20.

(FIV). *Viruses*. 3(11):2192-213.

Microbiol Immunol. 43(8):817-20.


comparison of the FIV and human immunodeficiency virus type 1 evolutionary patterns*. J Virol.* 68(4):2230-8.

**Chapter 17** 

© 2012 Tozon et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

and reproduction in any medium, provided the original work is properly cited.

© 2012 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

**Feline Immunodeficiency Virus (FIV)** 

**Infection in Cats: A Possible Cause** 

**of Renal Pathological Changes** 

Natasa Tozon, Mauro Pistello and Alessandro Poli

The feline immunodeficiency virus (FIV) is a lentivirus isolated from domestic cats with an acquired immunodeficiency syndrome-like condition, named feline AIDS (F-AIDS). The major immunological abnormalities observed in FIV-infected cats included a profound decline in the absolute number of the CD4+ T cells that caused the inversion of the CD4+/CD8+ T cell ratio and increased susceptibility to opportunistic infections and various clinic-pathological conditions [1]. FIV viruses encompass a large group of strains classified in subgroups from A to E, which are unevenly distributed geographically and have an intersubtype diversity > 26% [2]. The isolates used in our study were Petaluma, of group A, and Pisa-M2, a local isolate belonging to group B, which encloses all isolates hitherto sequenced and circulating in Italy [3 4]. Serological screenings performed in the past demonstrated that the virus is distributed worldwide and incidence varies from 1 – 14% in healthy cats and up to 44% in sick cats. As other lentiviruses, FIV is a complex retrovirus with structural genes *gag, pol* and *env*, and a few accessory genes [5]; *gag* encodes the capsid protein p24, used in most diagnostic tests, and other inner structural proteins, *pol* encodes the enzymes necessary for viral replication and therefore targeted by most anti-lentiviral drugs, and *env* encode the outer glycoprotein (gp95) and trans-membrane protein (gp36) serving as viral receptor and, being constantly under immunological pressure, the less conserved proteins among the different subtypes. Like the human immunodeficiency virus (HIV), the gp95 is comprised of variable and conserved regions and binds the CD134 molecule, the FIV primary receptor [6]. Studies on HIV have shown that some conserved epitopes are accessible for neutralizing antibodies, while the co-receptor binding site is composed by interspersed domains. The binding site remains largely hidden and is therefore inaccessible for mentioned antibody. Whereas overall HIV and FIV Env structure is maintained [7], HIV uses various coreceptors, including a range transmembrane domain G-protein-coupled receptors. In

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/51534

**1. Introduction** 

