The antiviral activity of a synthetic peptide derived from the envelope SU glycoprotein of feline immunodeficiency virus maps in correspondence of an amphipathic helical segment.
In a previous paper (Lombardi et al., Virology 220, 274-284, 1996), we-reported that a 20-amino acid synthetic peptide derived from a conserved region of the SU glycoprotein of feline immunodeficiency virus (FIV), i.e., 225EGPTLGNWAREIWATLFKKA244, bound the surface of FIV-permissive cells and inhibited FIV infection of CrFK and lymphoid cells. In this paper, we report, by the use of N- and C-terminus deleted synthetic analogs and by glycine scanning experiments that the minimal sequence needed for the full antiviral activity of the peptide maps in correspondence of amino acids 229LGNWAREIWATL240 and that either tryptophans residues at sequence position 232 or 237 are essential for such activity. Circular dichroism (CD) studies indicate that in the presence of a hydrophobic environment the 225E-A244 peptide adopts a structure containing an amphipathic alpha-helical segment of approximately 7 residues, corresponding to 2 helical turns, likely in correspondence of the sequence 231(N)WAREIW(A)238. Such a helical segment of FIV SU glycoprotein may play a role in viral envelope fusion role with the host cell membrane, thus proving critical for cell infection.
Massi
C
C
Department of Biomedicine, University of Pisa, Italy.
Indino
E
E
Lami
C
C
Fissi
A
A
Pieroni
O
O
La Rosa
C
C
Esposito
F
F
Galoppini
C
C
Rovero
P
P
Bandecchi
P
P
Bendinelli
M
M
Garzelli
C
C
D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology; D002415:Cats; D002942:Circular Dichroism; D016089:Immunodeficiency Virus, Feline / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D008561:Membrane Fusion / Q000502:physiology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000494:pharmacology; D010449:Peptide Mapping; D017433:Protein Structure, Secondary; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*
D000998:Antiviral Agents; D010446:Peptide Fragments; D014759:Viral Envelope Proteins