Differential utilization of CD134 as a functional receptor by diverse strains of feline immunodeficiency virus.
The feline homologue of CD134 (fCD134) is the primary binding receptor for feline immunodeficiency virus (FIV), targeting the virus preferentially to activated CD4+ helper T cells. However, with disease progression, the cell tropism of FIV broadens such that B cells and monocytes/macrophages become significant reservoirs of proviral DNA, suggesting that receptor utilization may alter with disease progression. We examined the receptor utilization of diverse strains of FIV and found that all strains tested utilized CD134 as the primary receptor. Using chimeric feline x human CD134 receptors, the primary determinant of receptor function was mapped to the first cysteine-rich domain (CRD1) of fCD134. For the PPR and B2542 strains, the replacement of CDR1 of fCD134 (amino acids 1 to 64) with human CD134 (hCD134) alone was sufficient to confer nearly optimal receptor function. However, evidence of differential utilization of CD134 was revealed, since strains GL8, CPGammer (CPG41), TM2, 0827, and NCSU1 required determinants in the region spanning amino acids 65 to 85, indicating that these strains may require a more stringent interaction for infection to proceed.
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
Brian J
BJ
Willett
Elizabeth L
EL
McMonagle
Susan
S
Ridha
Margaret J
MJ
Hosie
D000818:Animals; D000906:Antibodies / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002415:Cats; D002460:Cell Line; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D016089:Immunodeficiency Virus, Feline / Q000235:genetics* / Q000378:metabolism* / Q000472:pathogenicity; D051379:Mice; D008958:Models, Molecular; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism*; D014161:Transduction, Genetic; D014759:Viral Envelope Proteins / Q000378:metabolism
D000906:Antibodies; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D011991:Receptors, Virus; C505716:TNFRSF4 protein, human; C505717:Tnfrsf4 protein, mouse; D014759:Viral Envelope Proteins