title: WFDC1 expression identifies memory CD4 T-lymphocytes rendered vulnerable to cell-cell HIV-1 transfer by promoting intercellular adhesive junctions.
abstract: BACKGROUND
  Elucidating mechanisms that promote HIV-1 transfer between CD4+ T-lymphocytes and their subsequent loss is of importance to HIV-1 pathogenesis. We recently reported that whey acidic protein, ps20, promotes cell-free HIV-1 spread through ICAM-1 modulation. Since ICAM-1 is pivotal in cell conjugation and intercellular HIV-1 transfer, this study examines ps20 effects on HIV-1 spread between T lymphocytes.
  
  
  RESULTS
  We demonstrate intrinsic ps20 variability in primary CD4+ T-lymphocyte clonal populations and a significant positive correlation between endogenous ps20 levels and virus transfer involving fusion resulting in a spreading infection that could be reversed by the addition of reverse transcriptase inhibitors. Blocking anti-ps20 antibody or siRNA mediated ps20 knockdown, significantly reduced virus transfer. Conversely, virus transfer was promoted by ectopic ps20 expression or by exogenous addition of recombinant ps20. A higher frequency of virological synapse formation was evident in cocultures of HIV-1 infected donor T-cells with ps20high v ps20low/intermediate targets. Blocking ps20 inhibited T-lymphocyte conjugate formation and ICAM-1 expression, and was as potent as ICAM-1 in inhibiting HIV-1 transfer.
  
  
  CONCLUSIONS
  Therefore ps20 is a novel marker of CD4+ T-cells rendered vulnerable to HIV-1 infection by regulating the fundamental biologic process of intercellular conjugate formation and consequently of potential importance in HIV-1 pathogenesis.
authors.affiliation: Department of Infectious Diseases, King's College London, UK.
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Alvarez
authors.forename: Georgina
authors.initials: G
authors.lastname: Thorborn
authors.forename: James L
authors.initials: JL
authors.lastname: Reading
authors.forename: Shalini Kamu
authors.initials: SK
authors.lastname: Reddy
authors.forename: Annapurna
authors.initials: A
authors.lastname: Vyakarnam
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000502:physiology* / Q000821:virology*; D002448:Cell Adhesion; D002459:Cell Fusion; D015497:HIV-1 / Q000254:growth & development* / Q000472:pathogenicity*; D006801:Humans; D019169:Jurkat Cells; D011506:Proteins / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000502:physiology* / Q000821:virology*
chemical_list: D011506:Proteins; C484310:WFDC1 protein, human