The Journal of Antimicrobial Chemotherapy vol:68 pages:2026-37
Objectives: Carbohydrate binding agents (CBAs) represent a promising group of anti-HIV agents with potential microbicidal activity. A selection of CBAs with different glycan specificities should be evaluated for their inhibitory effect against HIV infection and transmission, and their interaction with vaginal commensal bacteria should be determined.
Methods: Following assay systems were used for the antiviral evaluation of CBAs: (i) cell-free virus infection of human CD4+ T-lymphocyte C8166 cells; (ii) syncytium formation in co-cultures of persistently HIV-1-infected HUT-78/HIV-1 and non-infected CD4+ SupT1 cells; (iii) Dendritic Cell-Specific Intercellular adhesion molecule-3 Grabbing Non-integrin (DC-SIGN)-directed capture of HIV-1 particles and (iv) transmission of DC-SIGN-captured HIV-1 particles to uninfected CD4+ C8166 cells. Also, the CBAs were examined for their interaction with vaginal commensal lactobacilli using several viability, proliferation and adhesion assays.
Results: The CBAs showed an efficient inhibitory activity in the nanomolar to low-micromolar range against four different events that play a crucial role in HIV-1 infection and transmission: cell-free virus infection, fusion between HIV-1-infected and non-infected cells, HIV-1 capture by DC-SIGN and transmission of DC-SIGN-captured virus to T-cells. Since potential candidate microbicide agents, such as CBAs, should not interfere with the normal human microbiota, we examined the effect of CBAs against different Lactobacillus strains, including a broad variety of vaginal strains, but also one gastrointestinal and several non-human bacterial isolates. None of the CBAs included in our studies inhibited the growth of the tested bacteria in several media, affected the viability of these bacterial isolates nor had any significant impact on the adhesion properties of the lactobacilli to human epithelial HeLa cell monolayers.
Conclusion: The CBAs included in this study were inhibitory to HIV-1 in several in vitro infection and transmission models, and may therefore qualify as potential microbicide candidate agents. The lack of significant impact on commensal vaginal lactobacilli is an important property of these CBAs in view of their potential microbicidal use.