Antiviral activity and conformational features of an octapeptide derived from the membrane-proximal ectodomain of the feline immunodeficiency virus transmembrane glycoprotein.
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 membrane-proximal 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.
Giannecchini
Simone
S
Retrovirus Center and Virology Section, Department of Experimental Pathology, University of Pisa, I-56127 Pisa, Italy.
Di Fenza
Armida
A
D'Ursi
Anna Maria
AM
Matteucci
Donatella
D
Rovero
Paolo
P
Bendinelli
Mauro
M
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002415:Cats; D002460:Cell Line; D016089:Immunodeficiency Virus, Feline / Q000187:drug effects* / Q000502:physiology; D008561:Membrane Fusion / Q000187:drug effects; D008958:Models, Molecular; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011487:Protein Conformation; D014759:Viral Envelope Proteins / Q000737:chemistry*; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D010455:Peptides; D014759:Viral Envelope Proteins