Bovine β–lactoglobulin modified by 3–hydroxyphthalic anhydride blocks the CD4 cell receptor for HIV

Sexual transmission is the most frequent (86%) route of adult HIV–1 transmission worldwide1. In the absence of a prophylactic anti–HIV vaccine, other methods of preventing infection should be implemented. Virucidal spermicides have been considered for this purpose, but their application is contraindicated by adverse effects2. Anti–HIV drugs3 or virus–neutralizing monoclonal antibodies4 are expensive, suggesting that their wide use in topical chemoprophylaxis is unlikely. This emphasizes the importance of developing other methods for preventing HIV transmission. The target cells for sexual and mucosal HIV transmission include T lymphocytes, monocytes/macrophages and dendritic cells5. Therefore, compounds blocking HIV–CD4 binding are expected to inhibit virus transmission. In exploring the possibility that chemical modification of food proteins might lead to compounds with anti–HIV–1 activity, we found that bovine (β–lactoglobulin (β–LG) modified by 3–hydroxyphthalic anhydride (3HP–β–LC) (1) blocked at nanomolar concentrations the binding to CD4 of human (HIV) and simian (SIV) immunodeficiency virus surface glycoproteins and monoclonal antibodies specific for the HIV binding site on CD4 and (2) inhibited infection by HIV–1, including primary virus isolates, by HIV–2 and by SIV. The inexpensive and widely available source (whey) for production of 3HP–β–LG suggests its potential application (nonparenteral) for diminishing the frequency of HIV transmission.