Title: CADA inhibits human immunodeficiency virus and human herpesvirus 7 replication by down-modulation of the cellular CD4 receptor
Authors: Vermeire, Kurt ×
Zhang, Ying
Princen, Katrien
Hatse, Sigrid
Samala, Meinrado F
Dey, Kaka
Choi, Heung-Jin
Ahn, Youngmi
Sodoma, Andrej
Snoeck, Robert
Andrei, Graciela
De Clercq, Erik
Bell, Thomas W
Schols, Dominique #
Issue Date: Oct-2002
Series Title: Virology vol:302 issue:2 pages:342-353
Abstract: The novel antiviral agent cyclotriazadisulfonamide (CADA) inhibited human immunodeficiency virus (HIV) (IC50, 0.3-3.2 microM) and human herpesvirus 7 (HHV-7) infection (IC50, 0.3-1.5 microM) in T-cell lines and PBMCs. When T-cells were pretreated with CADA for 24 h, they became markedly protected from viral infection. Flow cytometric analysis revealed a significant decrease in the expression of the CD4 glycoprotein, the primary receptor needed for entry of both viruses. Moreover, the antiviral activity of CADA correlated with its ability to down-modulate the CD4 receptor. CADA did not alter the expression of any other cellular receptor (or HIV coreceptor) examined. Time course experiments showed that CD4 down-modulation by CADA differs in mechanism from the effects of aurintricarboxylic acid, which binds directly to CD4, and phorbol myristate acetate, which activates protein kinase C. Further analysis of CD4 mRNA levels suggested that CADA was not involved in the regulation of CD4 expression at a transcriptional level, but very likely at (post) translational levels. This unique mechanism of action makes CADA an important lead in developing new drugs for treatment of AIDS, autoimmune diseases, and inflammatory disorders.
ISSN: 0042-6822
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
Laboratory of Experimental Oncology
× corresponding author
# (joint) last author

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