Sequential CD134-CXCR4 interactions in feline immunodeficiency virus (FIV): soluble CD134 activates FIV Env for CXCR4-dependent entry and reveals a cryptic neutralization epitope

J Virol. 2006 Mar;80(6):3088-91. doi: 10.1128/JVI.80.6.3088-3091.2006.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cats
  • Epitopes / chemistry
  • Epitopes / genetics
  • Epitopes / immunology
  • Gene Expression Regulation, Viral
  • Gene Products, env / chemistry
  • Gene Products, env / genetics
  • Gene Products, env / metabolism*
  • Genes, env
  • HIV Envelope Protein gp120 / chemistry
  • Immunodeficiency Virus, Feline / metabolism
  • Immunodeficiency Virus, Feline / pathogenicity*
  • Molecular Sequence Data
  • Neutralization Tests
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics
  • Peptide Fragments / immunology
  • Receptors, CXCR4 / metabolism*
  • Receptors, OX40
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Solubility

Substances

  • Epitopes
  • Gene Products, env
  • HIV Envelope Protein gp120
  • HIV envelope protein gp120 (305-321)
  • Peptide Fragments
  • Receptors, CXCR4
  • Receptors, OX40
  • Receptors, Tumor Necrosis Factor