Targeting the glycans of gp120: a novel approach aimed at the Achilles heel of HIV

Abstract

The development of drug resistance in HIV compromises the long-term efficacy of current therapies. Furthermore, vaccine development faces huge problems, mainly because of the low antigenicity and immunogenicity of the HIV envelope glycoprotein gp120 and the efficient hiding of highly immunogenic epitopes by its glycans. There is evidence that mutant HIV strains containing glycosylation site deletions trigger the production of specific neutralising antibodies to previously hidden gp120 epitopes. I present a hypothesis that development of resistance against drugs that target the glycans on gp120 would result in a marked enhancement of neutralisation of HIV by the immune system--ie, drugs directed against the carbohydrate component of gp120 will select for mutant virus strains that progressively gain deletions in the glycosylation sites of gp120. Previously hidden epitopes would then be uncovered, and the virus will become highly susceptible to markedly increased immunological neutralisation. I believe this novel approach may become an entirely new therapeutic concept that exploits the high mutation rate of HIV and allows drug therapy to act in concert with a triggered immune response to suppress HIV more efficiently. Moreover, this approach could be applied to treat other chronic infections by viruses that contain a glycosylated envelope (eg, hepatitis B and C).