Molecular mechanisms of FIV infection

Abstract

Feline immunodeficiency virus (FIV) is an important viral pathogen worldwide in the domestic cat, which is the smallest animal model for the study of natural lentivirus infection. Thus, understanding the molecular mechanisms by which FIV carries out its life cycle and causes an acquired immune deficiency syndrome (AIDS) in the cat is of high priority. FIV has an overall genome size similar to HIV, the causative agent of AIDS in man, and shares with the human virus genomic features that may serve as common targets for development of broad-based intervention strategies. Specific targets include enzymes encoded by the two lentiviruses, such as protease (PR), reverse transcriptase (RT), RNAse H, and integrase (IN). In addition, both FIV and HIV encode Vif and Rev elements essential for virus replication and also share the use of the chemokine receptor CXCR4 for entry into the host cell. The following review is a brief overview of the current state of characterization of the feline/ FIV model and development of its use for generation and testing of anti-viral agents.

Regulation of Lentivirus Neurovirulence by Lipopolysaccharide Conditioning: Suppression of CXCL10 in the Brain by IL-10

“…Viral load is a key marker of in vivo viral burden, and its measurement in blood is a useful indicator of systemic disease status (38,39). Animals that were repeatedly exposed to LPS showed signs of sickness behavior for ∼1-2 h after injection, as evidenced by reduced motor activity, sleep, and ruffled coat, but promptly recovered in all cases.…”

Feline Immunodeficiency

“…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 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 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).…”

Mutations in the feline immunodeficiency virus envelope glycoprotein confer resistance to a dominant–negative fragment of Tsg101 by enhancing infectivity and cell-to-cell virus transmission

“…32,39-44 Despite having very little sequence homology with HIV-1, we and others have shown that the molecular mechanisms and organization of functional domains for FIV virion assembly and release, proteolytic maturation of Gag and Env, Env-mediated receptor/co-receptor binding and membrane fusion, reverse transcription, integration, latency, Rev-dependent export of genomic RNA, and targeting of antiviral restriction factors are all highly conserved with those of HIV-1 and other primate lentiviruses. 32,44-62 For example, the PSAP motif in the C-terminal p2 domain of FIV Gag functions equivalently to the PTAP motif in HIV-1 Gag p6 in its role in FIV release and direct interaction with TSG101. 5,46 Unlike HIV-1, however, FIV does not contain a secondary YPXnL-type late domain and is insensitive to agents that would disrupt interactions with the Alix-V domain.…”