The use of Envelope for HIV therapeutics: from vaccines to co-receptors

The Envelope protein (Env) of the human immunodeficiency virus (HIV) has been a primary target and tool for antiviral drug and vaccine development since the discovery of the virus. The study of Env has led to a knowledge of the virus life-cycle, structure and immunological response that has helped lead HIV-directed therapeutic strategies in new, unexpected directions. In particular, the discovery of chemokine receptors as the HIV co-receptors in 1996 is allowing a new generation of antiviral and vaccine candidates to be developed that are based on the ability to block the function of Env in mediating viral entry. This review discusses the primary roles of Env throughout its course of investigation as a tool for vaccine development and as a target for drug screening, emphasising the recent role of Env in the discovery and exploration of the co-receptors. The use of gp120/chemokine binding assays, chemokine receptor structure-function studies and co-receptor polymorphisms are discussed in the context of the development of high-throughput screening assays, creation of immunogens with enhanced vaccine potential and targeting of the co-receptors CCR5 and CXCR4 by small-molecule inhibitors of HIV entry.