Mapping the domains of CD134 as a functional receptor for feline immunodeficiency virus.
The feline homologue of CD134 is the primary binding receptor for feline immunodeficiency virus (FIV), targeting the virus preferentially to activated CD4+ helper T cells. However, strains of FIV differ in utilization of CD134; the prototypic strain PPR requires a minimal determinant in the first cysteine-rich domain (CRD1) of feline CD134 to confer near-optimal receptor function, while strains such as GL8 require additional determinants in the CD134 CRD2. We map this determinant to a loop in CRD2 governing the interaction between the receptor and its ligand; the amino acid substitutions S78N-S79Y-K80E restored full viral receptor activity to the CDR2 of human CD134 in the context of feline CD134, with tyrosine-79 appearing to be the critical residue for restoration of receptor function.
Willett
Brian J
BJ
Retrovirus Research Laboratory, Institute of Comparative Medicine, Faculty of Veterinary Medicine, University of Glasgow, Bearsden Road, Glasgow G61 1QH, United Kingdom. b.willett@vet.gla.ac.uk
McMonagle
Elizabeth L
EL
Bonci
Francesca
F
Pistello
Mauro
M
Hosie
Margaret J
MJ
D019943:Amino Acid Substitution; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002415:Cats; D006367:HeLa Cells; D006801:Humans; D016089:Immunodeficiency Virus, Feline / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D008024:Ligands; D017434:Protein Structure, Tertiary; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism*; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism
D008024:Ligands; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D011991:Receptors, Virus; C505716:TNFRSF4 protein, human; D014443:Tyrosine