odeled shell of VSV -- which now looks like an uninfected T cell -- tricks HIV-infected cells into fusing with it instead. This enables VSV, which easily kills cells, to gain entry into the HIV-infected cell and destroy it. The modified VSV cannot infect normal cells because it lacks its normal surface protein. Thus, it targets, enters, multiplies in and kills only Tcells that, through the display of HIV gp120, signal that they are infected.

In their experiments, the Yale team infected human T cell lines with a laboratory strain of HIV. To these cells lines -- in which about half of the cells were now HIV-infected -- they added the novel VSV at either three or five days postinfection. This ultimately slashed infectious HIV to extremely low or undetectable levels, at least 300-fold to10 thousand-fold lower than the levels of HIV produced in control cells.

"Until there are data from animal models," Dr. Rose cautions, "we cannot gauge how well the potential treatment might work in people." But he regards it as "likely to be safe," and would like to see the concept tested in human clinical trials as soon as possible. Such discussions are already under way, but Dr. Rose estimates the possibility is at least a year away and that trials in animal models are a necessary first step.

The report says the novel VSV described would be most appropriate for limiting HIV production in people with late-stage disease, but the Yale team has moved on to develop VSV constructs that incorporate other HIV coreceptors such as CCR5 and CCR3 in an attempt to affect HIV strains that target macrophages and typically predominate in early HIV infection.

The virus involved, VSV, causes vesicular stomatitis, a disease mainly of cattle, horses and pigs that causes blister-like bumps on the hoofs and tongue. Nearly all animals recover completely from the illness.

Occasionally, people become infected with VSV through close contact with infected livestock or via laborato
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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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