Structure, function and antigenicity of the HIV1 envelope glycoproteins

Abstract

A critical component of an HIV vaccine will be the induction of broadly neutralizing antibodies. The exterior envelope glycoprotein gp120 and the transmembrane glycoprotein gp41 comprise the trimeric Env spike, mediate receptor binding, viral entry and are the sole targets for neutralizing antibodies. However, attempts to generate neutralizing antibodies using monomeric gp120 as the immunogen or portions of gp41 have not been met with great success. The limited elicitation of broadly neutralizing antibodies is likely due to escape mechanisms within Env from antibody-mediated neutralization elucidated by many structure/function studies and include : variable immunodominant regions, conformational masking and glycan shielding. Atomic level structure of the trimeric form of gp120 reflecting the native spike architecture found on the virus would aid in the design of better immunogens. Such improved immunogens may more efficiently elicit broadly neutralizing antibodies and be a critical component to a preventive HIV vaccine.