WFDC1/ps20 Is a Novel Innate Immunomodulatory Signature Protein of Human Immunodeficiency Virus (HIV)-Permissive CD4+CD45RO+Memory T Cells That Promotes Infection by Upregulating CD54 Integrin Expression and Is Elevated in HIV Type 1 Infection

• DOI: 10.1128/jvi.00939-07
• Publication Date: 2007-10-18T01:04:48Z
• Authors: R. Alvarez; J. Reading; D. F. L. King; M. Hayes; P. Easterbrook; F. Farzaneh; S. Ressler; F. Yang; D. Rowley; A. Vyakarnam
• Keywords: CD4-Positive T-Lymphocytes; 0303 health sciences; 610; Proteins; Intercellular Adhesion Molecule-1; Cell Line; 3. Good health; 03 medical and health sciences; T-Lymphocyte Subsets; 616; HIV-1; Humans; Gene Silencing; Cells, Cultured

Understanding why human immunodeficiency virus (HIV) preferentially infects some CD4(+) CD45RO(+) memory T cells has implications for antiviral immunity and pathogenesis. We report that differential expression of a novel secreted factor, ps20, previously implicated in tissue remodeling, may underlie CD4 are targeted. show (i) there is significant positive correlation between endogenous ps20 mRNA diverse T-cell populations vitro infection, (ii) ps20(+) permissive cell can be made less by antibody blockade- or small-interference RNA-mediated knockdown (iii) conversely, ps20(low) more adding exogenously engineering stable retroviral transduction. normally detectable after activation interleukin-2 expansion, such oligoclonal comprise ps20(positive) ps20(low/negative) isogenic clones at an early differentiation stage (CD45RO(+)/CD25(+)/CD28(+)/CD57(-)). This pattern altered chronic HIV where ex vivo express elevated ps20. promoted entry via fusion augmented CD54 integrin expression; both these effects were reversed anti-ps20 antibody. therefore propose to signature HIV-permissive promotes infection autocrine paracrine manner coopted fundamental role promoting adhesion its benefit. Disrupting the pathway provide anti-HIV strategy.