title: Broad anti-HIV activity of the Oscillatoria agardhii agglutinin homologue lectin family.
abstract: OBJECTIVE
  Oscillatoria agardhii agglutinin homologue (OAAH) proteins belong to a recently discovered lectin family. The founding member OAA and a designed hybrid OAAH (OPA) recognize similar but unique carbohydrate structures of Man-9, compared with other antiviral carbohydrate-binding agents (CBAs). These two newly described CBAs were evaluated for their inactivating properties on HIV replication and transmission and for their potential as microbicides.
  
  
  METHODS
  Various cellular assays were used to determine antiviral activity against wild-type and certain CBA-resistant HIV-1 strains: (i) free HIV virion infection in human T lymphoma cell lines and PBMCs; (ii) syncytium formation assay using persistently HIV-infected T cells and non-infected CD4+ T cells; (iii) DC-SIGN-mediated viral capture; and (iv) transmission to uninfected CD4+ T cells. OAA and OPA were also evaluated for their mitogenic properties and potential synergistic effects using other CBAs.
  
  
  RESULTS
  OAA and OPA inhibit HIV replication, syncytium formation between HIV-1-infected and uninfected T cells, DC-SIGN-mediated HIV-1 capture and transmission to CD4+ target T cells, thereby rendering a variety of HIV-1 and HIV-2 clinical isolates non-infectious, independent of their coreceptor use. Both CBAs competitively inhibit the binding of the Manα(1-2)Man-specific 2G12 monoclonal antibody (mAb) as shown by flow cytometry and surface plasmon resonance analysis. The HIV-1 NL4.3(2G12res), NL4.3(MVNres) and IIIB(GRFTres) strains were equally inhibited as the wild-type HIV-1 strains by these CBAs. Combination studies indicate that OAA and OPA act synergistically with Hippeastrum hybrid agglutinin, 2G12 mAb and griffithsin (GRFT), with the exception of OPA/GRFT.
  
  
  CONCLUSIONS
  OAA and OPA are unique CBAs with broad-spectrum anti-HIV activity; however, further optimization will be necessary for microbicidal application.
authors: Rega Institute for Medical Research, University of Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium geoffrey.ferir@rega.kuleuven.be.
authors: Geoffrey
authors: G
authors: Férir
authors: Rega Institute for Medical Research, University of Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
authors: Dana
authors: D
authors: Huskens
authors: Rega Institute for Medical Research, University of Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
authors: Sam
authors: S
authors: Noppen
authors: Department of Structural Biology, University of Pittsburgh School of Medicine, Biomedical Science Tower 3, 3501 Fifth Avenue, Pittsburgh, PA 15260, USA.
authors: Leonardus M I
authors: LM
authors: Koharudin
authors: Department of Structural Biology, University of Pittsburgh School of Medicine, Biomedical Science Tower 3, 3501 Fifth Avenue, Pittsburgh, PA 15260, USA.
authors: Angela M
authors: AM
authors: Gronenborn
authors: Rega Institute for Medical Research, University of Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
authors: Dominique
authors: D
authors: Schols
mesh_terms: D000373:Agglutinins / Q000378:metabolism / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000378:metabolism / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000494:pharmacology; D002460:Cell Line; D024882:Drug Resistance, Viral; D015726:Giant Cells / Q000187:drug effects / Q000821:virology; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D037102:Lectins / Q000378:metabolism / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000821:virology; D008826:Microbial Sensitivity Tests; D054300:Oscillatoria / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D000373:Agglutinins; D019380:Anti-HIV Agents; D001426:Bacterial Proteins; D015699:HIV Envelope Protein gp120; D037102:Lectins; C514793:gp120 protein, Human immunodeficiency virus 1
keywords: OAA; OAAH (OPA); PBMCs; anti-HIV activity; broad spectrum; glycosylation; microbicide