The membrane-proximal tryptophan-rich region in the transmembrane glycoprotein ectodomain of feline immunodeficiency virus is important for cell entry.
The mechanisms whereby feline immunodeficiency virus (FIV) adsorbs and enters into susceptible cells are poorly understood. Here, we investigated the role exerted in such functions by the tryptophan (Trp)-rich motif present membrane-proximally in the ectodomain of the FIV transmembrane glycoprotein. Starting from p34TF10, which encodes the entire genome of FIV Petaluma, we produced 11 mutated clones having the Trp-rich motif scrambled or variously deleted or substituted. All mutated progenies adsorbed normally to cells, but the ones with severe disruptions of the motif failed to generate proviral DNA. In the latter mutants, proviral DNA formation was restored by providing an independent source of intact FIV envelope glycoproteins or by addition of the fusing agent polyethylene glycol, thus clearly indicating that their defect resided primarily at the level of cell entry. In addition, the replication-competent mutants exhibited a generally enhanced susceptibility to selected entry inhibitory synthetic peptides, suggestive of a reduced efficiency of the entry step.
Retrovirus Center and Virology Section, Department of Experimental Pathology, University of Pisa, I-56127 Pisa, Italy.
Simone
S
Giannecchini
Francesca
F
Bonci
Mauro
M
Pistello
Donatella
D
Matteucci
Olimpia
O
Sichi
Paolo
P
Rovero
Mauro
M
Bendinelli
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004705:Endocytosis; D016089:Immunodeficiency Virus, Feline / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D009154:Mutation; D016415:Sequence Alignment; D014162:Transfection; D014364:Tryptophan / Q000737:chemistry; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication
D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; D014364:Tryptophan