Lentivirus vector mobilization and spread by human immunodeficiency virus

The rapid advancement of lentivirus-based gene transfer systems and their d emonstrated utility in a variety of in vitro and in vivo settings has heigh tened the need for assays to evaluate the safety of these vectors prior to human clinical trials. Two major concerns relating to the use of lentivirus -based vectors in a clinical setting are the presence of contaminating repl ication-competent retroviruses in vector preparations and the efficiency of vector mobilization and spread by wild-type helper virus (rescue). This ar ticle describes an in vitro system to study the rescue of lentivirus-based vectors by wild-type HIV. We show that lentivirus-based vectors can be read ily rescued from T cell lines and to a lesser extent from primary human lym phocytes by wildtype HIV, resulting in the spread of mobilized vector parti cles to previously untransduced cells. Furthermore, we show that vector mob ilization can be prevented by antiretroviral drugs such as AZT. In contrast to recently published reports by Bukovsky et al. and An et al., the lentiv irus vectors used in these studies had little or no effect on the replicati on and spread of HIV in transduced cells [Bukovsky et al. (1999). J. Virol. 73, 7087-7092; An et al. (1999). J. Virol. 73, 7671-7677]. Whereas vector spread is a significant concern for most gene therapy applications, in the context of gene therapy for HIV infection it may have beneficial effects.