A NOVEL MURINE RETROVIRUS IDENTIFIED DURING TESTING FOR HELPER VIRUS IN HUMAN GENE-TRANSFER TRIALS

An important requirement for the use of retroviral vectors in human ge ne transfer experiments is the avoidance of human exposure to replicat ion-competent (helper) retroviruses, To meet this requirement, we used a sensitive marker rescue assay for helper virus to screen vector-tra nsduced cells prior to reinfusion into patients, This assay utilized M us dunni cells harboring a retroviral vector that can be rescued by he lper retroviruses, The assay indicated the presence of helper virus in medium exposed to hematopoietic cells from all patients tested, inclu ding six patients with various cancers and one patient with Gaucher's disease, whether or not the patient cells had been exposed to retrovir al vectors. All of the helper viruses were in a single interference gr oup, We have now shown that treatment of the M. dunni marker rescue as say cells with 5-iodo-2'-deoxyuridine or hydrocortisone can activate p roduction of an apparently identical helper virus, which we have named M, dunni endogenous virus (MDEV), Thus, production of virus in the as says of patient materials was likely due to exposure of the marker res cue assay cells to the hydrocortisone present in the hematopoietic cel l growth medium, MDEV does not belong to any of the known murine leuke mia virus groups by interference analysis, and we have called the new group multitropic because of the wide range of cells from different sp ecies that MDEV can infect.