INFECTION BY RETROVIRAL VECTORS OUTSIDE OF THEIR HOST-RANGE IN THE PRESENCE OF REPLICATION-DEFECTIVE ADENOVIRUS

Retrovirus infection is normally limited to cells within a specific ho st range which express a cognate receptor that is recognized by the pr oduct of the env gene. We describe retrovirus infection of cells outsi de of their normal host range when the infection is performed in the p resence of a replication-defective adenovirus (dl312). In the presence of adenovirus, several different ecotropic vectors are shown to infec t human cell lines (HeLa and PLC/PRF), and a xenotropic vector is show n to infect murine cells (NIH 3T3). Infectivity is demonstrated by -br omo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-Gal) staining, sele ction with G418 for neomycin resistance, and PCR identification of the provirus in infected cells. Infectivity is quantitatively dependent u pon both the concentration of adenovirus (10(6) to 10(8) PFU/ml) and t he concentration of retrovirus. Infection requires the simultaneous pr esence of adenovirus in the retrovirus infection medium and is not sti mulated by preincubation and removal of adenovirus from the cells befo re retrovirus infection. The presence of adenovirus is shown to enhanc e the uptake of fluorescently labeled retrovirus particles into cells outside of their normal host range, demonstrating that the adenovirus enhances viral entry into cells in the absence of the recognized cogna te receptor. This observation suggests new opportunities for developin g safe retroviral vectors for gene therapy and new mechanisms for the pathogenesis of retroviral disease.