Session 46Poster Presentations DC-SIGN and Related Molecules Session Day and Time: Thursday 1:30 - 3:30 pm Room: Hall D
372 Study of the Role of Mannose Binding Lectine and DC-SIGN in Discordant Partners in a Haiti Cohort H. Mohri*1, T. Sakai1, N. Mushtaq1, D. Fitzgerald2,3, J. W. Pape2, W. D. Johnson1, D. D. Ho1 1Aaron Diamond AIDS Res Ctr, New York, NY; 2Groupe Haitien D'Etude du Sarcome de Kaposi et des Infections; Opportunistes, Port au Prince, Haiti; and 3Cornell Univ Med Coll, New York, NY
Background: The envelope protein of HIV-1, gp120 is enriched in high-mannose oligosaccharides. Therefore, glycoprotein-lectin interactions may be crucial for HIV-1 transmission. Mannose binding lectin (MBL) is known to delay the disease progression. However, its role in HIV-1 transmission is well characterized. At mucosal sites, dendritic cells are thought to facilitate HIV-1 transmission via a C-type lectin, DC-SIGN. However, its role in HIV-1 transmission has not yet been demonstrated. In this study, we investigated the role of these factors in HIV-1 transmission in high-risk, sero-negative, discordant partners.
Methods: We studied 25 discordant partners and 23 low risk controls in a Haiti cohort. The concentration of MBL in plasma was measured by ELISA. To assess the ability to express DC-SIGN in vivo, blood monocytes were cultured with GM-CSF and IL-4 and differentiated into immature dendritic cells. The expression level of DC-SIGN was measured by flowcytometry. The mRNA of isoforms, DC-SIGN1A and DC-SIGN1B, was amplified by RT-PCR, and the relative expression of their membrane type and secretory type was assessed based on their specific length of PCR product.
Results: The concentration of MBL varied significantly in both groups (1~4,679 ng/ml). The mean concentration of MBL was 1,468 ng/ml in controls and 1,141 ng/ml in discordant partners, and they were not statistically different (p = 0.39). The mean intensity of DC-SIGN staining was of similar levels in both groups. The expression profile of isoforms was uniform, e.g., DC-SIGN1A was predominantly of a membrane type and DC-SIGN1B was more of a secretory type. Their expression profile in discordant partners were not different from that in controls.
Conclusions: The similar levels of MBL in the discordant partners and controls suggested that MBL is not protective against HIV-1 transmission. In addition, although we did not measure the expression level of DC-SIGN in vivo, our in vitro results did not support the hypothesis that the differential expression of DC-SIGN is responsible for the protection of discordant partners from HIV-1 transmission.
