title: Annexin A2 antibodies but not inhibitors of the annexin A2 heterotetramer impair productive HIV-1 infection of macrophages in vitro.
abstract: During sexual transmission of human immunodeficiency virus (HIV), macrophages are initial targets for HIV infection. Secretory leukocyte protease inhibitor (SLPI) has been shown to protect against HIV infection of macrophages through interactions with annexin A2 (A2), which is found on the macrophage cell surface as a heterotetramer (A2t) consisting of A2 and S100A10. Therefore, we investigated potential protein-protein interactions between A2 and HIV-1 gp120 through a series of co-immunoprecipitation assays and a single molecule pulldown (SiMPull) technique. Additionally, inhibitors of A2t (A2ti) that target the interaction between A2 and S100A10 were tested for their ability to impair productive HIV-1 infection of macrophages. Our data suggest that interactions between HIV-1 gp120 and A2 exist, though this interaction may be indirect. Furthermore, an anti-A2 antibody impaired HIV-1 particle production in macrophages in vitro, whereas A2ti did not indicating that annexin A2 may promote HIV-1 infection of macrophages in its monomeric rather than tetrameric form.
authors.affiliation: Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Woodham
authors.affiliation: Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.|Present Address: Division of Oncology and Pathology, Lund University, Lund, Sweden.
authors.forename: Adriana M
authors.initials: AM
authors.lastname: Sanna
authors.affiliation: Department of Molecular Microbiology & Immunology, University of Southern California, 1450 Biggy St., NRT 7507, Los Angeles, CA, 90033, USA.
authors.forename: Julia R
authors.initials: JR
authors.lastname: Taylor
authors.affiliation: Department of Molecular Microbiology & Immunology, University of Southern California, 1450 Biggy St., NRT 7507, Los Angeles, CA, 90033, USA.
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Skeate
authors.affiliation: Department of Obstetrics & Gynecology, University of Southern California, Los Angeles, CA, USA.
authors.forename: Diane M
authors.initials: DM
authors.lastname: Da Silva
authors.affiliation: School of Pharmacy, Centre for Biomolecular Sciences, University of Nottingham, Nottingham, NG7 2RD, UK.
authors.forename: Lodewijk V
authors.initials: LV
authors.lastname: Dekker
authors.affiliation: Department of Molecular Microbiology & Immunology, University of Southern California, 1450 Biggy St., NRT 7507, Los Angeles, CA, 90033, USA. Martin.Kast@med.usc.edu.
authors.forename: W Martin
authors.initials: WM
authors.lastname: Kast
mesh_terms: D017306:Annexin A2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000906:Antibodies / Q000378:metabolism; D002498:Centrifugation; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D047468:Immunoprecipitation; D008264:Macrophages / Q000821:virology*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D014779:Virus Replication
chemical_list: C472822:ANXA2 protein, human; D017306:Annexin A2; D000906:Antibodies; D015699:HIV Envelope Protein gp120; C514793:gp120 protein, Human immunodeficiency virus 1
keywords: Annexin A2; Annexin A2 heterotetramer; HIV-1; Inhibitor; Macrophage; Receptor