Anti-human immunodeficiency virus (HIV) drug HOE/BAY 946 increases membrane hydrophobicity of human lymphocytes and specifically suppresses HIV-protein synthesis.

Autor: Biesert, Lothar, Adamski, Michalina, Zimmer, Guido, Suhartono, Hary, Fuchs, Jürgen, Unkelbach, Uwe, Mehlhorn, Rolf, Hideg, Katman, Milbradt, Rainer, Rübsamen-Waigmann, Helga
Zdroj: Medical Microbiology & Immunology; Dec1990, Vol. 179 Issue 6, p307-321, 15p
Abstrakt: The polysulfated polyxylan HOE/BAY 946, which has been tested in two pilot studies in ARC/AIDS patients and in asymptomatic HIV carriers in Germany, was believed to act by inhibiting virus attachment to the cell. However, the drug was also found to reduce the amount of HIV particles released from infected peripheral blood mononuclear cells (PBMC) in vitro. Furthermore, preincubation of PBMC with the drug led to a partial inhibition of a following HIV infection, suggesting that the drug also affects virus entry. Electron Paramagnetic Resonance (EPR) measurements on uninfected human lymphocytes using 5-proxyl-nonane as spin label demonstrated smaller hyperfine coupling constant (a) values in the presence of HOE/BAY 946 or dextran sulfate 5000. Accordingly, h/h ratios were decreased, indicating increased plasma membrane hydrophobicity and a membrane-stabilizing effect of the drugs. Culture of the chronically HIV-infected monocytic cell line U937/HIV-2 in the presence of HOE/BAY 946 specifically and drastically reduced the release of virions and the intracellular synthesis of viral proteins as determined by radioimmunoprecipitation and reverse transcriptase assays. In conclusion, although the EPR studies showed a physico-chemical effect on membrane polarity, HOE/BAY 946 and dextran sulfate clearly affect processes beyond the cell membrane. Thus, in contrast to previous reports suggesting that polysulfated sugars affect HIV only by inhibiting virus binding to uninfected cells, they clearly inhibit HIV in infected cells as well and appear to have a pleiotropic mode of action. Such drugs may be less likely to result in viral resistance after prolonged application than substances acting only on one step in the life cycle of the virus. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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