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About Sickkids
About SickKids

February 28, 2006

Researchers describe novel inhibitor of HIV infection

Researchers at SickKids and Canadian Blood Services have found a novel molecule which may prevent many types of HIV from infecting different kinds of cells. This research is reported in the February 20 issue of AIDS.

“We have described a novel soluble molecule, based on a modified molecule from normal cells that can prevent many different types of HIV from infecting many different kinds of cells,” said Dr. Clifford Lingwood, senior scientist in Infection, Immunity, Injury and Repair Research and Professor of Laboratory Medicine & Pathobiology and Biochemistry at the University of Toronto. “We had previously shown that this modified glycolipid, called adamantylGb3, made by Dr. Murugespillai Mylvaganum, binds to the HIV protein responsible for binding the virus to cells. We have now found adamantylGb3 to inhibit the infection of cells in vitro by all strains of HIV. This also fits with our finding that cells from people in which the normal Gb3 accumulates due to a metabolic defect, are resistant to HIV”

Can you describe the mechanism by which AdamantylGb3 inhibits infection?
AdamantylGb3 works by binding to the virus and preventing the fusion of the virus with the host cell. This is a different mechanism from most anti HIV treatments. Even drug resistant HIV strains remain susceptible to adamantylGb3 which could therefore, be of clinical benefit when other drugs have failed.

“AdamantylGb3 may provide the basis of a new treatment or the prevention of transmission of HIV and/or AIDS,” added Dr Don Branch, Canadian Blood Services scientist, Associate Professor, Departments of Medicine and Laboratory Medicine & Pathobiology, University of Toronto. “We now need to determine whether or not HIV is able to develop resistance to this compound over time. We expect it will not”.

One potential application for the soluble molecule in the prevention of HIV is its utility in a topical microbicide, a gel that women can apply before intercourse to prevent transmission of the virus. To this end, one of the next tasks for the research team is the development of a topological format to prevent sexual transmission.

Additional next steps for the research team include determining the best concentrations and formulations of the molecule in animal models.

Other researchers on this work include Nicole Laud, Xue-Zhong Ma and Darinka Sakac of Canadian Blood Services, Jacques Fantini of Institut Mediterraneen de Recherche en Nutrition, Anu Puri and Robert Blumenthal of the National Cancer Institute Frederick and Murugespillai Mylvaganam, Davin Chark and Beth Binnington of SickKids.

This research was funded by the Canadian Institutes of Health Research, the Ontario HIV Treatment Network and SickKids Foundation.


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The Hospital for Sick Children