No abstract

Feline immunodeficiency virus (FIV) provides a valuable animal model by which criteria for lentivirus control strategies can be tested. Previous studies have shown that a 20-mer synthetic peptide of the membraneproximal ectodomain of FIV transmembrane glycoprotein, designated peptide 59, potently inhibited the growth of tissue culture-adapted FIV in feline fibroblastoid CrFK cells. In the present report we describe the potential of this peptide to inhibit the replication of primary FIV isolates in lymphoid cells. Because antiviral activity of peptide 59 was found to map to a short segment containing three conserved Trp residues, further analyses focused on a derivative of eight amino acids ( 770 W-I 777 ), designated C8. Peptide C8 activity was found to be dependent on conservation of the Trp motif, to be removed from solution by FIV absorbed onto substrate cells, and to be blocked by a peptide derived from the N-terminal portion of FIV transmembrane glycoprotein. Structural studies showed that peptide C8 possesses a conformational propensity highly uncommon for peptides of its size, which may account for its considerable antiviral potency in spite of small size.

The lentivirus feline immunodeficiency virus (FIV) is a widespread pathogen of the domestic cat that is mainly transmitted through bites, although other means of transmission are also possible. Its prevalence ranges from 1 to 10% in different cat populations throughout the world, thus representing a large reservoir of naturally infected animals. FIV resembles the human immunodeficiency virus (HIV) in many respects. Similarities include the structural features of the virion, the general organization and great variability of the genome, the life cycle in the infected host, and most importantly, the pathogenic potential. Infection is associated with laboratory signs of immunosuppression as well as with a large variety of superinfections, tumors, and neurological manifestations. Our understanding of FIV is steadily improving and is providing important clues to the pathogenesis of immunodeficiency-inducing lentiviruses. The cellular receptor for FIV is different from the feline equivalent of the human CD4 molecule used by HIV; nevertheless, the major hallmark of infection is a progressive loss of CD4+ T lymphocytes as in HIV infection. The mechanisms by which FIV escapes the host's immune responses are being actively investigated. FIV causes lysis of infected T cells and also appears to predispose these cells to apoptosis. Infection of macrophages and other cell types has also been documented. For reasons yet to be understood, antibody-mediated neutralization of fresh FIV isolates is very inefficient both in vitro and in vivo. Vaccination studies have provided some encouraging results, but the difficulties encountered appear to match those met in HIV vaccine development. FIV susceptibility to antiviral agents is similar to that of HIV, thus providing a valuable system for in vivo preclinical evaluation of therapies. It is concluded that in many respects FIV is an ideal model for AIDS studies.

So far, vaccination experiments against feline immunodeficiency virus have used in vitro-grown virus to challenge the vaccinated hosts. In this study, cats were vaccinated with fixed feline immunodeficiency virusinfected cells and challenged with plasma obtained from cats infected with the homologous virus diluted to contain 10 cat 50% infectious doses. As judged by virus culture, PCRs, and serological analyses performed over an 18-month period after the challenge, all of the vaccinated cats were clearly protected. Interestingly, prior to challenge most vaccinees lacked antibodies capable of neutralizing a fresh isolate of the homologous virus.

The genetic diversity of 32 Italian isolates of feline immunodeficiency virus (FIV) was studied. Isolates were obtained from domestic cats living in different areas. Sequence data were obtained from a 308 bp fragment of the p25 region of the gag gene. Phylogenetic relationships among these sequences and previously published sequences were determined. All the Italian isolates could be assigned to subtype B ; however, four isolates formed two separate clusters and may represent genetic out-