May 14, 2007

“Entry Claw” Helps the HIV Virus Infect Host Cells

Five red rods connect a spherical magenta virus with a yellow core to a blue surface Computer-generated image of the contact region between HIV-1 and the T cell membrane. The virus is magenta with a yellow core, the contact rods are red and the cell membrane is blue. Sougrat et al., PLoS Pathogens, Vol. 3, No. 5, e63.

Scientists have described a new structure at the interface between the AIDS virus and the host cells it infects that appears to help the virus gain entry to its target.

Human immunodeficiency virus (HIV), the virus that causes AIDS, kills or damages cells in the body's immune system, progressively destroying the body's ability to fight infections and certain cancers. Researchers have known that when HIV infects its target cell, a viral surface protein called gp120 must bind to a protein on the cell surface. However, it has been difficult to clearly see how these proteins come together using traditional imaging techniques.

Dr. Sriram Subramaniam of NIH's National Cancer Institute (NCI) and his colleagues used a technique called electron tomography to capture highly detailed, 3-dimensional images of HIV and the related simian virus (SIV) interacting with immune system cells called T cells. In the May 4, 2007, issue of the online journal PLoS Pathogens, the team reported that when HIV or SIV makes contact with a T cell, a tight cluster of 5 to 7 rod-shaped viral structures forms between the virus and the cell. This unexpected arrangement was dubbed the "entry claw."

The research group observed that gp120 molecules across the rest of the viral surface were frequently absent after the entry claw was formed. The authors suggested that the virus might shed its remaining surface proteins after T cell contact.

“The discovery of the entry claw raises many fundamental questions about viral entry into host cells,” said Subramaniam. “How does the viral genetic code actually transfer to the host cell? What are the other intermediate steps of the entry claw formation, and can they be visualized? As we continue to improve the technology for 3D imaging, we believe we will answer these and related questions.”

The more that researchers understand how HIV infects cells, the more likely they will be able to develop better therapies to prevent infection.

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