Inhibition of feline immunodeficiency virus infection in vitro by envelope glycoprotein synthetic peptides.
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.
Lombardi
S
S
Department of Biomedicine, University of Pisa, Italy.
Massi
C
C
Indino
E
E
La Rosa
C
C
Mazzetti
P
P
Falcone
M L
ML
Rovero
P
P
Fissi
A
A
Pieroni
O
O
Bandecchi
P
P
Esposito
F
F
Tozzini
F
F
Bendinelli
M
M
Garzelli
C
C
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002415:Cats; D002460:Cell Line; D002942:Circular Dichroism; D015726:Giant Cells / Q000821:virology; D016089:Immunodeficiency Virus, Feline / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D014759:Viral Envelope Proteins / Q000138:chemical synthesis / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D010455:Peptides; D014759:Viral Envelope Proteins