Large-molecular-weight carbohydrate-binding agents as HIV entry inhibitors targeting glycoprotein gp120

Abstract

Purpose of review: Given the continuing expansion of the HIV pandemic, more emphasis on new methods of treatment and prevention of the HIV infection is urgently needed.

Recent findings: Several carbohydrate-binding agents, basically monomeric, dimeric or tetrameric proteins (lectins), are endowed with a pronounced anti-HIV activity in cell culture. They inhibit the viral entry (fusion) process and can block HIV infections by cell-free virions, as well as virus cell-cell transmission. Prolonged exposure to carbohydrate-binding agents slowly and progressively selects for deletions of glycans at N-glycosylation sites in HIV gp120. Such mutant virus strains retain full sensitivity to other anti-HIV drugs. Moreover, virus strains that contain deleted glycans in their gp120 envelope may trigger the immune system to produce neutralizing antibodies against the uncovered immunogenic epitopes on HIV gp120, contributing further to the elimination of the mutant virus particles from the bloodstream. Efficient expression of carbohydrate-binding agents by commensal bacteria has been achieved and may be an interesting novel approach to protect the vaginal mucosa against HIV infection/transmission.

Summary: Carbohydrate-binding proteins are a unique group of natural products that may qualify as efficient microbicides and as a potential tool to prevent mother-to-infant virus transmission.