Structure of an HIV-2 gp120 in Complex with CD4

Area of Science:

• Structural biology
• Virology
• Immunology

Background:

• Human immunodeficiency virus type 2 (HIV-2) is a nonpandemic form of the virus causing acquired immunodeficiency syndrome (AIDS).
• Most HIV-2-infected patients experience long-term nonprogression of the disease.
• The envelope glycoproteins of HIV-1 and HIV-2 share 30-40% amino acid identity and are the primary targets for neutralizing antibodies.

Purpose of the Study:

• To investigate the structural basis for the reduced pathogenicity of HIV-2 compared to HIV-1.
• To understand the interaction between HIV-2 gp120 and the host receptor CD4 at a molecular level.

Main Methods:

• X-ray crystallography was used to determine the structure of an HIV-2 gp120 envelope glycoprotein bound to the host receptor CD4.
• The obtained structure was analyzed and compared to existing structures of HIV-1 gp120.

Main Results:

• A 3.0-Å resolution structure of the HIV-2 gp120 bound to CD4 was successfully solved.
• The structure revealed significant structural similarity between HIV-2 gp120 and HIV-1 gp120, despite considerable divergence in their amino acid sequences.
• This structural similarity suggests conserved functional or binding mechanisms.

Conclusions:

• The determined structure provides a crucial first step in understanding the molecular mechanisms underlying the reduced pathogenicity of HIV-2.
• Conserved structural features in the gp120 glycoproteins may contribute to the distinct clinical outcomes observed in HIV-1 and HIV-2 infections.