Monday, May 14, 2007

How HIV Infects Cells

Retroviruses such as HIV-1 enter cells via the interaction between glycoproteins on the surface of the virus particle and cell surface receptors. Since this is such an important step in virus replication, knowledge of the structures of these glycoproteins and the molecular details of their interactions with cell surface receptors is of great importance.
Electron tomography is a powerful approach to determining the three-dimensional structures of large sub-cellular assemblies such as virus-receptor interactions. The images are built up from a series of optical sections generated in the electron microscope. In this paper, the authors used the method to examine the interaction of purified SIV virions with CD4-positive target cells.
The envelope glycoproteins of primate lentiviruses, including human and simian immunodeficiency viruses (HIV and SIV), are heterodimers of a transmembrane glycoprotein (gp41), and a surface glycoprotein (gp120), which binds CD4 on the surface of target cells to initiate virus entry.
The trimeric virus envelope glycoprotein surface spikes are around 120 Å long and approximately 120 Å wide at the distal end. Docking of the virus on the T cell surface occurs via a neck-shaped contact region that is about 400 Å wide and consists of a closely spaced cluster of five to seven rod-shaped features, each about 100 Å long and 100 Å wide. This distinctive structure is not observed when viruses are incubated with T lymphocytes in the presence of anti-CD4 antibodies or drugs which block the interaction of gp120 and CD4.
This data shows that these lentiviruses make contact with T cells via a unique structure which the authors call the entry claw. This is typically composed of six clustered rods that span the contact region. Further investigation of the structure of this entry claw and its formation could lead to new insights into the design of more effective drugs to inhibit HIV infection.
This video is based on a paper recently published in PLoS Pathogens:
Electron Tomography of the Contact between T Cells and SIV/HIV-1: Implications for Viral Entry. PLoS Pathogens 2007 3 (5) e63

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