Selective activity of various antiviral compounds against HHV-7 infection.
Human herpesvirus virus type 7 (HHV-7) is a T-lymphotropic herpesvirus which uses the CD4 receptor as main receptor to infect its target cells. Measuring the decrease of CD4 expression during HHV-7 infection is a convenient and accurate method to monitor the efficacy of antiviral agents against HHV-7 infection. Different classes of compounds, such as heparin, pentosan polysulfate (PS), dextran sulfate (DS), aurintricarboxylic acid (ATA), phosphonoformic acid (PFA), 9-(2-phosphonylmethoxyethyl)adenine (PMEA), 2-amino-7-[(1,3-dihydroxy-2-propoxy) methyl] purine (S2242), polyvinylalcohol sulfate (PVAS) and the co-polymer of vinylalcohol sulfate with acrylic acid (PAVAS), acyclovir (ACV), ganciclovir (GCV), penciclovir (PCV), brivudin (BVDU), cidofovir (HPMPC), lobucavir, (R)-9-[4-hydroxy-2-(hydroxymethyl)butyl]guanine] (H2G), (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA) and sorivudine (BVaraU), were evaluated for their anti-HHV-7 activity in the SupT1 T cell line and in purified CD4+ T lymphocytes. Antiviral activity was monitored by inhibition of: (i) CD4 expression down-regulation; (ii) giant cell formation and (iii) apoptosis induction. In general, PS, DS, PVAS, PAVAS, ATA, PFA, PMEA, S2242, lobucavir and HPMPC had comparable anti-HHV-7 activity in the two cell lines, irrespective of the parameters followed to monitor antiviral activity. One of the exceptions was heparin which had an IC50 of 9.6 microg/ml in SupT1 cells and >250 microg/ml in CD4+ T lymphocytes. The compounds PCV, GCV, H2G and PMPA showed some activity in CD4+ T lymphocytes, but not in SupT1 cells. ACV, BVDU and BVaraU did not show activity in either cell system. None of the chemokines tested, such as platelet factor-4 (PF-4), eotaxin, stromal cell-derived factor 1alpha(SDF-1alpha) and RANTES, had detectable activity against HHV-7. In contrast, the HIV-1 envelope glycoprotein, gp120, and the two anti-CD4 mAbs, 13B8-2 and OKT4, were clearly active against HHV-7 infection.
Zhang
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Y
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium. ying.zhang@rega.kuleuven.ac.be
Schols
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D
De Clercq
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E
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology*; D017209:Apoptosis; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000821:virology*; D002460:Cell Line; D002478:Cells, Cultured; D018925:Chemokines / Q000494:pharmacology; D003588:Cytopathogenic Effect, Viral; D005434:Flow Cytometry; D015726:Giant Cells; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology; D015497:HIV-1; D016199:Herpesvirus 7, Human / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans
D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D015704:CD4 Antigens; D018925:Chemokines; D015699:HIV Envelope Protein gp120