期刊
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
卷 69, 期 10, 页码 2746-2758出版社
OXFORD UNIV PRESS
DOI: 10.1093/jac/dku220
关键词
OAA; OAAH (OPA); glycosylation; broad spectrum; anti-HIV activity; PBMCs; microbicide
资金
- KU Leuven [GOA 10/014, PF/10/018]
- Foundation of Scientific Research (FWO) [G-0485-08, G-0528-12]
- Foundation Dormeur, Vaduz
- CHAARM project of the European Commission
- NIH [GM080642]
Objectives: 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 CBAresistant 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 Mana(1-2) Man-specific 2G12 monoclonal antibody (mAb) as shown by flow cytometry and surface plasmon resonance analysis. The HIV-1 NL4.32G12res, NL4.3MVNres and IIIBGRFTres strains were equally inhibited as the wild-type HIV-1 strains by these CBAs. Combination studies indicate that OAA and OPA act synergistically with Hippeastrumhybrid agglutinin, 2G12mAb 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.
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