17th International AIDS Conference Mexico City, Mexico - August 13 - 18, 2008

THE TOLL-LIKE RECEPTOR 2 LIGAND ZYMOSAN INHIBITS HIV-1 REPLICATION IN HUMAN PRIMARY CELLS

Int Conf AIDS. 2008 Aug 13-18;17 Abstract No. MOAA0105

H.K. Pimenta-Inada¹, L.G. Jucá¹, C.C. Cirne-Santos¹, D.C. Bou-Habib,² C. Dumith ^2
1Oswaldo Cruz Foundation, Rio de Janeiro, Brazil, ²Oswaldo Cruz Foundation, Oswaldo Cruz Institute, Rio de Janeiro, Brazil

BACKGROUND: Zymosan, an insoluble carbohydrate from the yeast Saccharomyces cerevisae, is a ligand of the Toll-like receptor 2 (TLR2). After phagocytosed by macrophages, zymosan can induce a prolonged inflammatory response, leading to secretion of inflammatory mediators, such as TNF-α and IFN-γ. It is not clear so far whether zymosan can modulate viral replication in HIV-1-infected cells.

The aim of this study was to analyse whether zymosan is endowed with the potential to modulate HIV-1 replication in human primary cells.

METHODS: PBMCs were obtained from healthy donors by density gradient centrifugation, and macrophages by plastic adherence of PBMCs. Cells were infected with the cloned HIV-1 isolate Ba-L (R5-tropic) or with R5 and X4-tropic primary isolates of HIV-1, and exposed to different concentrations of Zymosan. In some experiments cells were treated with Zymosan before HIV-1 infection. Levels of the β-chemokines MIP-1α, MIP-1β and RANTES and viral replication were evaluated in culture supernatants by ELISA. HIV-1 pro-viral integration was assessed by PCR methods.

RESULTS: Zymosan inhibited HIV-1 replication in PBMCs, varying from 60% with 25 µg/mL to 66% with 100 µg/mL, and more than 90% inhibition in macrophages with concentrations from 6 µg/mL to 50 µg/mL. Similar results were also obtained with Pam3Cys, a synthetic ligand of TLR-2. Treatment of PBMCs during 24 h with zymosan prior to HIV-1 infection inhibited viral replication by 88%. Zymosan enhanced the production of MIP-1α, MIP-1β and RANTES by PBMCs and macrophages. Apparently, zymosan did not inhibit HIV-1 pro-viral integration in PBMCs.

CONCLUSIONS: Our results show that the TLR2 ligand zymosan inhibits HIV-1 replication in human PBMCs and macrophages, when added either before or after infection. It is possible that the increment of β-chemokine production contributes to this inhibition. Our results warrant further studies on the mechanisms underlying the antiretroviral activity of zymosan and the role of TLR2 in this phenomenon.

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2008-08-13
MOAA0105

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