EXPLORATIONS
Taking Aim at HIV
It may be possible to block male to female HIV transmission in heterosexual intercourse. So say Michael Lederman of the Case School of Medicine and University Hospitals of Cleveland, and his research colleagues from across the country who have identified the target for blocking that transmission.
“Effective methods for blocking the transmission of HIV are urgently needed,” says Prof. Lederman, the Scott R. Inkley Professor of Medicine and director of the Center for AIDS Research at Case and UH, and lead author of the paper that appeared in the October 14 issue of Science.
“Our study focuses on a strategy for preventing transmission of HIV through the vagina. We have identified a potential target, a mechanism critical for the transmission at vaginal sites of infection, that may offer a simple strategy for preventing HIV transmission.
“The vast majority of HIV infections are sexually transmitted, most commonly through heterosexual sex,” Prof. Lederman continues. “But there has been substantial debate as to how the virus actually gets into cells at these sites of transmission, called mucosal sites. HIV can use certain cell surface molecules such as CCR5 to gain entry into cells.”
People with a mutation whose CD4 cells’ surface lack CCR5 are almost completely protected from acquiring HIV infection, he explains. But HIV can also use other target molecules to get into other cells. “Thus, there was some uncertainty as to how HIV was transmitted at mucosal sites and therefore which pathways needed to be blocked in order to prevent HIV transmission there,” Prof. Lederman says. The research team decided to test the hypothesis that blocking CCR5 alone would be sufficient to protect rhesus macaques from vaginal challenge with a virus like HIV. A natural immune messenger (chemokine) called RANTES can bind to CCR5 and, by binding, forces the cell to internalize the CCR5 receptor so HIV cannot bind to it, he says. The team developed an altered RANTES molecule to target CCR5 and make it unavailable to the virus.
In their experiment, the team applied a highly concentrated solution containing the altered chemokine to the vaginal membranes of rhesus macaque monkeys and challenged them with high doses of a virus that combined the outer surface of HIV and the inner workings of SIV—so called SHIV. The solution protected the macaques without any detectable side effects.
The research team admits that much work needs to be done before an affordable, easy-to-use method is developed. But its study represents an important step toward that end, they say. “The door is open to the development of a topical agent that could prevent infection with HIV in humans.”
GEORGE STAMATIS
Stop. Look. Design.
Stop, look, and design might become the new mantra for business managers. Instead of executives approaching problems by accepting the default alternatives and deciding among them, Case Professors Richard J. Boland Jr. and Fred Collopy, the editors of the newly published book Managing As Designing (Stanford University Press), show how managers can design their way to new solutions.
Managing As Designing evolved from a workshop, organized by the book’s editors just days before the dedication of the Frank Gehry-designed Peter B. Lewis Building, home of Case’s Weatherhead School of Management.
The book’s thirty-seven chapters are written by workshop participants (including Mr. Gehry)—designers from such fields as architecture, art, business, dance, education, music, and psychology, who discussed how they design and what managers can learn from the art of design. 
SUSAN GRIFFITH
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