Algal lectins as potential HIV microbicide candidates

Abstract

The development and use of topical microbicides potentially offers an additional strategy to reduce the spread of the Human Immunodeficiency Virus (HIV). Carbohydrate-binding agents (CBAs) that show specificity for high mannose carbohydrates on the surface of the heavily glycosylated envelope of HIV are endowed with potent anti-HIV activity. In fact, a number of algal lectins such as cyanovirin-N, microvirin, microcystis viridis lectin, scytovirin, Oscillatoria agardhii agglutinin and griffithsin are considered as potential microbicide candidates to prevent the sexual transmission of HIV through topical applications. They not only inhibit infection of cells by cell-free virus but they can also efficiently prevent virus transmission from virus-infected cells to uninfected CD4(+) target T-lymphocytes and DC-SIGN-directed capture of HIV-1 and transmission to CD4(+) T lymphocytes. This review focuses on the structural properties and carbohydrate specificity of these algal lectins, their antiviral activity against HIV and several other enveloped viruses, their safety profile and viral resistance patterns.

Keywords: HIV; algae; carbohydrate-binding agents; gp120 envelope; lectin; microbicide; virus entry.

Figure 1

Internal amino acid sequence alignment of Cyanovirin-N (CV-N) (a); Microvirin (MVN) (b); Microcystis viridis lectin (MVL) (c); Scytovirin (SVN) (d); Oscillatoria agardhii agglutinin (OAA) (e); Griffithsin (GRFT) (f). Identical residues are indicated by “*” and similar residues by “:”. Disulfide bonds between cysteines are marked with solid lines above the sequence.

Figure 2

Chemical structure of Man₉GlcNAc₂.

Figure 3

Overview of the unique antiviral activities of carbohydrate-binding agents (CBAs). Algal lectins have been shown to efficiently inhibit the infection of CD4⁺ T cells and macrophages by cell-free HIV particles (a); inhibit syncytia formation between HIV-infected cells and uninfected target CD4⁺ T cells (b); inhibit the capture of HIV particles by DC-SIGN-expressing cells such as dendritic cells (DCs) (c); and inhibit the transmission of DC-SIGN-captured HIV to CD4⁺ target T cells (d).

Figure 4

Inhibition of HIV-induced giant cell formation. Light microscopic pictures of the following T cell line cultures: SupT1 cells (a); HUT-78 cells persistently infected with HIV-1 IIIB (b); Co-culture of SupT1 cells and HUT-78/HIV-1 IIIB cells (several giant cells are indicated with arrows) (c); Co-culture of SupT1 cells and HUT-78/HIV-1 IIIB cells in the presence of 140 nM MVN (d) or 1 nM GRFT (e).