Herpesvirus saimiri pathogenicity enhanced by thymidine kinase of herpes simplex virus

Herpesvirus saimiri can be used as an efficient gene expression Vector for human T lymphocytes and thus may allow applications in experimental leukemi a therapy. We constructed recombinant viruses for the functional expression of the thymidine kinase (TK) of herpes simplex virus type 1 (HSV) as a sui cide gene. These viruses reliably allowed the targeted elimination of trans duced nonpermissive human T cells in vitro after the administration of ganc iclovir. To test the reliability of this function under the most stringent permissive conditions, in this study we analyzed the influence of the prodr ugs ganciclovir and acyclovir in common marmosets on the acute leukemogenes is induced by either wild-type herpesvirus saimiri C488 or by a recombinant derivative expressing TK of HSV. Antiviral drug treatment did not influenc e the rapid development of acute disease. In contrast, the presence of the HSV tk gene resulted in a faster disease progression. In addition, HSV TK-e xpressing viruses showed faster replication than wild-type virus in culture at low serum concentrations. Thus, HSV TK accelerates the replication of h erpesvirus saimiri and enhances its pathogenicity. This should be generally considered when HSV TK is applied as a transgene in replication-competent DNA virus vectors for gene therapy. (C) 2000 Academic Press.