**3. Human immunodeficiency virus type 1 (HIV-1) x Feline immunodeficiency virus (FIV)**

Like the HIV, FIV belongs to the genus *Lentivirus* of the Retroviridae family. Since the discovery of human immunodeficiency virus type 1 (HIV-1) in 1982 there is an urgent need for animal models to study the pathogenesis of HIV-1 infection and possibilities for interventional strategies (Elder et al., 2008). FIV was descript in 1987, and since then, FIV has been proposed as a model for HIV studies, because, among non-primate vertebrates, FIV infection in the cat may be the closest model of HIV infection and acquired immunodeficiency syndrome (AIDS).

FIV is phylogenetically (though not antigenically) related to HIV-1. FIV and HIV share many features in their genomes in comprising three major open reading frames (ORF), gag, pol and env, especially in the pol gene and FIV also has a very similar life cycle to that of HIV (Table 2) (Savarino et al., 2007; Elder et al., 2008; Elder et al., 2010).


**Table 2.** Comparative viral genes encoded. Modified from Elder et al., 2010.

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

Feline Immunodeficiency 365

proteins, serving as valuable models to study the pathophysiology of HIV.A vaccine against FIV, whose development has been the object of considerable international research effort, has intrinsic value as well as the potential to provide a powerful proof of concept in

 **FIV HIV** 

Blood contact Yes Yes Mucosal contact Yes Yes Vertically via prenatal Yes Yes Postnatal routes Yes Yes

CD4+ T cell Yes Yes Macrophage Yes Yes Dentritic cell Yes Yes Subset B cells Yes ? Microglia Yes Yes

CD4 No Yes CD134 Yes No CXCR4 Yes Yes CCR5 No Yes

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

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

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

of FeLV and gp70 defines the virus subgroup (Hartmann, 2006; Lutz et al., 2009).

**Table 4.** Comparative properties of FIV and HIV. Modified from Elder et al., 2010.

than that caused by FIV infection (Hartmann, 2006; Lutz et al., 2009).

vaccination against human AIDS (Klonjkowski et al., 2009).

**Transmission**

**Target cell**

**Receptors utilized**

**4. Feline leukemia virus** 

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 transmission of HIV occurs mainly via mucosal routes.

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


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

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

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 proteins, serving as valuable models to study the pathophysiology of HIV.A vaccine against FIV, whose development has been the object of considerable international research effort, has intrinsic value as well as the potential to provide a powerful proof of concept in vaccination against human AIDS (Klonjkowski et al., 2009).


**Table 4.** Comparative properties of FIV and HIV. Modified from Elder et al., 2010.
