title: HIV envelope binding by macrophage-expressed gp340 promotes HIV-1 infection.
abstract: The scavenger receptor cysteine-rich protein gp340 functions as part of the host innate immune defense system at mucosal surfaces. In the genital tract, its expression by cervical and vaginal epithelial cells promotes HIV trans-infection and may play a role in sexual transmission. Gp340 is an alternatively spliced product of the deleted in malignant brain tumors 1 (DMBT1) gene. In addition to its innate immune system activity, DMBT1 demonstrates instability in multiple types of cancer and plays a role in epithelial cell differentiation. We demonstrate that monocyte-derived macrophages express gp340 and that HIV-1 infection is decreased when envelope cannot bind it. Inhibition of infection occurred at the level of fusion of M-, T-, and dual-tropic envelopes. Additional HIV-1 envelope binding molecules, such as dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN), mannose-binding lectin, and heparan sulfate, enhance the efficiency of infection of the cells that express them by increasing the local concentration of infectious virus. Our data suggest that gp340, which is expressed by macrophages in vivo, may function to enhance infection in much the same manner. Its expression on tissue macrophages and epithelial cells suggests important new opportunities for HIV-1 pathogenesis investigation and therapy.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Georgetta
authors.initials: G
authors.lastname: Cannon
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Yi
authors.forename: Houping
authors.initials: H
authors.lastname: Ni
authors.forename: Earl
authors.initials: E
authors.lastname: Stoddard
authors.forename: David A
authors.initials: DA
authors.lastname: Scales
authors.forename: Donald I
authors.initials: DI
authors.lastname: Van Ryk
authors.forename: Irwin
authors.initials: I
authors.lastname: Chaiken
authors.forename: Daniel
authors.initials: D
authors.lastname: Malamud
authors.forename: Drew
authors.initials: D
authors.lastname: Weissman
mesh_terms: D000906:Antibodies / Q000276:immunology; D002135:Calcium-Binding Proteins; D002460:Cell Line; D004268:DNA-Binding Proteins; D015658:HIV Infections / Q000276:immunology*; D006801:Humans; D008264:Macrophages / Q000276:immunology*; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000276:immunology*; D025521:Tumor Suppressor Proteins; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology*
chemical_list: D000906:Antibodies; D002135:Calcium-Binding Proteins; C108174:DMBT1 protein, human; D004268:DNA-Binding Proteins; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D054299:env Gene Products, Human Immunodeficiency Virus