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Trojan Horse Virus Controls Hiv Infection

National Institute of Allergy and Infectious Diseases (NIAID) grantees at Yale University have converted a common livestock virus into a Trojan horse that selectively targets HIV-infected cells and then destroys them. As reported Sept. 5 in the journal Cell, this strategy effectively controlled HIV infection in laboratory-grown T cells and dramatically reduced infectious HIV to levels that were barely or no longer detectable.

"This is a completely new approach, targeting a virus to an infected cell," explains the study's senior scientist, John K. Rose, Ph.D., from Yale's Departments of Pathology and Cell Biology. "The concept could be used to develop a whole new class of agents that are useful for controlling disease."

"Although additional in vitro and animal studies need to be performed before this novel virus can be tested in humans," comments NIAID Director Anthony S. Fauci, M.D., "this concept of cell-targeted delivery has enormous potential applications for HIV, cancer or other diseases."

In their report, Dr. Rose, Matthias J. Schnell, Ph.D., and their colleagues describe how they modified the vesicular stomatitis virus (VSV) genome, deleting its envelope gene and replacing it with the genes for a pair of cell surface receptor -- CD4 and the coreceptor CXCR4 -- normally found on human T cells. These receptors enable HIV to attach to, enter and infect T cells.

These receptors also permit cell-to-cell HIV infection to occur. HIV-infected cells flag themselves for destruction by the body's immune system by displaying HIV's outer coat protein. But this protein, HIV gp120, is the same one that attaches to the T-cell receptors and leads to infection. Cell-to-cell infection occurs when the HIV gp120 on an infected cell first hitches up to the receptors on an uninfected T cell, resulting in the fusion of the cell and viral membranes, and transfer of virus from the infected to the uninfected cell.

Turning around what occurs naturally, the rem
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Contact: Laurie K. Doepel
ldoepel@nih.gov
301-402-1663
NIH/National Institute of Allergy and Infectious Diseases
5-Sep-1997


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