Bovine beta-lactoglobulin modified by 3-hydroxyphthalic anhydride blocks the CD4 cell receptor for HIV

被引:76
作者
Neurath, AR
Jiang, SB
Strick, N
Lin, K
Li, YY
Debnath, AK
机构
[1] Laboratory of Biochemical Virology, Lindsley F. Kimball Research Inst., New York Blood Center, New York
关键词
D O I
10.1038/nm0296-230
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Sexual transmission is the most frequent (86%) route of adult HIV-1 transmission worldwide(1). 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 effects(2). Anti-HIV drugs(3) or virus-neutralizing monoclonal antibodies(4) 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 cells(5). 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 beta-lactoglobulin (P-LG) modified by 3-hydroxyphthalic anhydride (3HP-beta-LG) (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-beta-LG suggests its potential application (nonparenteral) for diminishing the frequency of HIV transmission.
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页码:230 / 234
页数:5
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