Mixed retrovirus infections frequently result in viral pseudotyping in which the genome of a virus is encapsulated within virions possessing a distinct host range from that encoded by the packaged genome. Pseudotyping between different classes of murine retroviruses has been extensively documented in vitro and in vivo and can result in profound changes in viral replication and pathology. A number of non-human retroviruses exhibit infectivity for various heterologous cell lines which often include human cells. Thus there is a possibility of generating heterologous mixed retroviral infections in humans upon the administration of clinical reagents developed in non-human systems. Pseudotyping between retroviruses from heterologous species (e.g., murine and primate retroviruses) has also been documented in mixed in vitro infections, as has pseudotyping between retroviruses and viruses of other families (e.g., rhabdoviruses). The effects of heterologous pseudotyping on viral replication and pathology in vivo have not been extensively studied and represent a potential concern for the development of clinical reagents in heterologous cells.