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Research conducted at The New York Hospital-Cornell University Medical College has found that a natural component of human saliva has a very powerful effect in blocking the growth of laboratory strains of HIV as well as AIDS viruses taken directly from patients. This finding could lead to the development of natural inhibitors to HIV transmission.

In a study published in the January 5 issue of the Journal of Experimental Medicine, Dr. Jeffrey Laurence, Director of the Laboratory for AIDS Virus Research; Dr. Ralph Nachman, Chairman of the Department of Medicine; Dr. Roy L. Silverstein, Chief of the Division of Hematology-Oncology; and a team of biomedical scientists describe how they have identified a natural sugar-protein, concentrated in saliva, known as TSP (thrombospondin), and discovered its remarkable ability to block the growth of the AIDS virus.

Recognizing that over the past years several labs have found a variety of substances in human saliva that partially inhibit the growth of HIV, Dr. Laurence and his research team delved further into this phenomenon.

Dr. Laurence said, "We began by exploring why there is so little HIV virus in saliva, while large amounts of the virus are found in other body fluids; and why human saliva is so effective at blocking the growth of the AIDS virus in the test tube. This led us to the discovery of TSP."

According to Dr. Laurence, "We made the observation that thrombospondin type 1 (TSP-1) can block HIV-1 infection of primary human cells and transform human cell lines of T lymphocyte and monocyte lineages. TSP is effective against both laboratory-adapted strains of HIV-1 and HIV-1 patient isolates. It is active at physiologic concentrations. Saliva experiments indicate that TSP-1 is a major component of the natural HIV inhibitory capacity of saliva."

TSP is of particular interest as a natural inhibitor, as others have shown that it may promote wound healing, and suppression of some bacterial infections. Higher levels of TSP in the saliva of some male, as opposed to female, animals may relate to the more frequent wounding of male animals. Wound licking, with application of saliva molecules that could inhibit infection, would then be very beneficial.

Speaking of the application of this research, Dr. Nachman said, "This is an exciting finding that is another step forward in our research efforts aimed at preventing AIDS transmission. TSP derivatives could potentially be used vaginally, rectally and orally in condoms, foams, suppositories, mouthwashes and toothpastes to inhibit transmission of the AIDS virus."

While TSP is a very large molecule that would be unwieldy to use directly in patients, the Cornell research team also investigated the mechanism of action of TSP. They found that peptides—small pieces of the larger TSP—could block binding of the AIDS virus to its receptor on immune cells. This offers the potential for direct use of these smaller molecules to prevent sexual transmission of HIV.

Funding for this work was provided by the Dental, Heart/Lung/Blood, and Allergy/Immunology Institutes of the NIH.