Sequential CD134-CXCR4 interactions in feline immunodeficiency virus (FIV): soluble CD134 activates FIV Env for CXCR4-dependent entry and reveals a cryptic neutralization epitope.
Recombinant soluble CD134 (sCD134) facilitated feline immunodeficiency virus (FIV) entry into CXCR4-positive, cell surface CD134-negative target cells. sCD134-activated entry was dose dependent and CXCR4 dependent. We used the sCD134 activation system to explore the neutralization by four anti-V3 monoclonal antibodies (MAbs). V3 MAbs weakly neutralized FIV infection using target cells expressing both CD134 and CXCR4 but potently inhibited sCD134-activated entry into target cells expressing CXCR4 alone. These findings provide direct evidence for a sequential interaction of FIV Env with CD134 and CXCR4 and reveal the presence of a cryptic epitope in V3 that is masked in the mature envelope oligomers.
de Parseval
Aymeric
A
The Scripps Research Institute, Department of Molecular Biology, MB-14, 10550 N. Torrey Pines Rd., La Jolla, California 92037, USA. parseval@scripps.edu
Grant
Chris K
CK
Sastry
K Jagannadha
KJ
Elder
John H
JH
D000595:Amino Acid Sequence; D000818:Animals; D002415:Cats; D000939:Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D015967:Gene Expression Regulation, Viral; D015686:Gene Products, env / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015752:Genes, env; D015699:HIV Envelope Protein gp120 / Q000737:chemistry; D016089:Immunodeficiency Virus, Feline / Q000378:metabolism / Q000472:pathogenicity*; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D019718:Receptors, CXCR4 / Q000378:metabolism*; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D012995:Solubility
D000939:Epitopes; D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D019718:Receptors, CXCR4; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor