From the natural evolution to the genetic manipulation of the host-range of retroviruses

The discovery that retroviruses share many features with retrotransposons led to the proposal that retroviruses evolved from cellular movable elements and became independent genetic entities, which started a parasitic life on their own. It has been further hypothesized that in the course of this evolutionary process, retrotransposons incorporated a cellular membrane glycoprotein gene into their genome, which finally became the envelope gene of the virus. Equipped with a error-prone polymerase and a high recombination rate during replication, the resulting genetic element has been equipped with a powerful machinery to change and modify itself, in particular the envelope gene, not only to escape the immune system, but also to change the host species. The HIV-1 epidemiology may serve as the best example of this still on-going evolutionary process. Since retroviruses insert their genome into that of the host cell as part of their life cycle, they have been extensively utilized as gene transfer vectors (retroviral vectors). Recently, experiments have been initiated to modify the envelope of retroviral vectors in the laboratory to alter the host range for specific gene transfer applications. This review highlights aspects of the natural evolution and the genetic modification of the retroviral envelope protein. Its implication on the safety of retroviral vectors in human gene therapy is also discussed.