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S ‐adenosyl methionine decarboxylase activity is required for the outcome of herpes simplex virus type 1 infection and represents a new potential therapeutic target
Author(s) -
Greco Anna,
Callé Aleth,
Morfin Florence,
Thouvenot Danielle,
Cayre Myriam,
Kindbeiter Karine,
Martin Laetitia,
Levillain Olivier,
Diaz JeanJacques
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-2108fje
Subject(s) - herpes simplex virus , spermidine , polyamine , virology , hsl and hsv , biology , spermine , enzyme , virus , microbiology and biotechnology , biochemistry
All the available antiherpetic drugs are directed against viral proteins. Their extensive clinical use has led to the emergence of resistant viral strains. There is a need for the treatment of herpes infections due to resistant strains, especially for immunocompromised patients. To design new kinds of drugs, we have developed a strategy to identify cellular targets. Herpes simplex virus type 1 (HSV‐1) infection is concomitant to a repression of most host protein synthesis. However, some cellular proteins continue to be efficiently synthesized. We speculated that some of them could determine the outcome of infection. Since two polyamines, spermidine and spermine, are components of the HSV‐1 virions, we investigated whether enzymes involved in their synthesis could be required for viral infection. We show that inhibition of S ‐adenosyl methionine decarboxylase, a key enzyme of the polyamine metabolic pathway, prevents HSV‐1 infection. Inhibition of polyamine synthesis prevents infection of culture cells with HSV‐1 laboratory strains as well as clinical isolates that are resistant to the conventional antiviral drugs acyclovir and foscarnet. Our data provide the opportunity to develop molecules with a novel mechanism of action for the treatment of herpes infection.