Inhibition of Feline Immunodeficiency Virus Infectionin Vitroby Envelope Glycoprotein Synthetic Peptides

Abstract

Sixty-six 20- to 23-amino-acid synthetic peptides, partially overlapping by 10-12 amino acids, spanning the entire sequence of the envelope SU and TM glycoproteins of the Petaluma isolate of FIV, have been used to investigate the Env domains involved in viral infection. Peptides 5 to 7, spanning amino acids 225E-P264 located in a conserved region of the SU protein, and peptides 58 to 61, spanning amino acids 767N-P806 and encompassing hypervariable region 8 of TM protein, exhibited a remarkable and specific antiviral effect against the homologous and one heterologous isolate, as judged by inhibition of FIV-induced syncytium formation and p25 production in CrFK cells. Peptides 5 and 7, but not peptides 58 and 59, also inhibited viral replication of a fresh FIV isolate on nontransformed lymphoid cells. By flow cytometry, peptides 5, 7, 58, and 59 were shown to bind the surface of FIV permissive cells. The antiviral activity of peptides 5 and 7, however, was time-dependent, as inhibition of FIV replication was seen when the peptides were administered before or within 3 hr after virus inoculation; in contrast, TM peptides 58 and 59 exerted a potent inhibitory effect when added up to 24 hr after virus inoculation. Circular dychroism analysis showed that peptide 5 folds to a helical conformation in the presence of a hydrophobic environment. Although the basis for the antiviral action of the peptides is not understood, our data suggest that the inhibitory peptides may act by interacting with cell-surface molecules involved in viral infection.

AIDS Vaccination Studies Using an Ex Vivo Feline Immunodeficiency Virus Model: Failure To Protect and Possible Enhancement of Challenge Infection by Four Cell-Based Vaccines Prepared with Autologous Lymphoblasts

“…one-tenth of the viral RNA copies, a finding in line with the fact that FIV had only been fixed onto PLB from without. (iii) The ID-2 and ID-3 vaccines had viral contents similar to that of ID-1, a finding consistent with the fact that contained peptides inhibited FIV entry at steps subsequent to attachment (35). (iv) Mock-1 and mock-2 immunogens were virus negative by all of the parameters investigated.…”

“…For the ID-2 and ID-3 immunogens, the formulation was modified slightly to include two synthetic peptide inhibitors of FIV active at different steps of cell entry and potentially capable of stabilizing the viral Env in an optimal conformation for putative ID epitopes expression. The inhibitors were peptides 5 (for ID-2) and 59 (for ID-3), derived from the amino-terminal region of the surface gp and from the membrane-proximal domain of the transmembrane gp of FIV (35) and designated here SU 5 and TM 59 , respectively. The conditions of AT2-FIV-cell contact were chosen on the basis of observations with HIV-1 (10, 21) partly confirmed with FIV (8), showing that at 4°C Env adsorption to cells and its initial consequent changes take place within minutes, but the eventual modifications that lead to fusion do not occur until the temperature is switched to 37°C.…”

Antiviral Activity and Conformational Features of an Octapeptide Derived from the Membrane-Proximal Ectodomain of the Feline Immunodeficiency Virus Transmembrane Glycoprotein

“…The surface and TM gp of FIV and HIV-1 exhibit a common structural framework and appear to play similar roles in cell entry (6, 11, 19, 23, 46-48, 54, 60, 67, 68). We have previously screened 20-to 23-mer peptides covering the entire Env of FIV and found especially potent in vitro antiviral activity associated with peptides derived from two regions, one located in the N-terminal domain of the surface gp and the other located membrane proximally in the ectodomain of the TM gp (37). In subsequent studies (40), we focused on peptides of the surface gp, because the most efficacious of the TM peptides, referred to as peptide 59 ( Fig.…”

In vitro inhibition of feline leukaemia virus infection by synthetic peptides derived from the transmembrane domain

“…These peptides can directly interact with the central coiled coil of the TM, thereby preventing the formation of the trimerof-hairpins and thus the induction of the membrane fusion [17]. Effective inhibitory peptides, mapped to an amphipatic α-helical region in the ectodomain of the viral TM, have been described, for example, for HIV [13,14] and for the feline immunodeficiency virus (FIV) [15,20]. Moreover, an HIV inhibitor (T-20) has been produced commercially (Hoffmann-LaRoche, Basel, Switzerland, and Trimeris, Inc., Durham, NC, USA) [13,14,21] and is currently included in antiretroviral therapy protocols.…”