VRC01 gp120 complex: Difference between revisions

HIV-1 has a high level of antigenic and genetic diversity.  HIV-1 has also evolved mechanisms to evade the humoral immune response.  These aspects of HIV-1 have made it difficult to develop a vaccine.  After several years of infection, 10 to 25% of HIV-1 infected individuals develop neutralizing antibodies.  Some antibodies target the transmembrane gp41 molecules of the HIV-1 viral spike, however most target the surface protein gp120. <ref name="wu">PMID: 21835983</ref> VRC01 and VRC01-like antibodies bind to gp120 and are able to neutralize about 90% of HIV-1 isolates.  Structural analysis has shown which characteristics of antibodies are essential to its binding with gp120<ref>PMID: 22789610</ref>.  Discovery of the structure of these antibodies can help develop an effective HIV-1 vaccine.

HIV-1 enters its host by binding viral gp120, a surface glycoprotein of HIV, to the host cell’s CD4 receptor.  This interaction induces conformational changes in gp120<ref name="wu" />. This conformational change results in the exposure of a binding site for the co-receptor, usually CCR5 OR CXCR4. (Li) The conformational changes also result in the formation of a pre-hairpin intermediate conformation in which gp41, a transmembrane glycoprotein of HIV, rearranges its molecules so that its N-terminal peptides form a trimer of helices that present a fusion peptide to the target cell.  Once fusion occurs between the fusion peptide and the target cell membrane, HIV is able to enter and infect the target cell. (Tran) VRC01 binds to CD4’s binding site on gp120, preventing the CD4 receptor from binding to HIV and infecting the cell<ref name="wu" />.