ABSTRACT

The first retrovirus was discovered by Paton Rous as a filterable agent which could transmit cancer in chickens. A large number of mammalian genes important in malignant cell transformation have thus been identified by the study of the natural history of these viruses and of tumours produced as a by-product of the normal viral life cycle. The host range of retroviral vectors is determined by the viral envelope glycoproteins and the target cell surface receptors to which they bind. Provirus integration in the host cell genome can result in both gene activation and gene inactivation. Provirus integration could also decrease the expression of a gene by disruption of either its cognate regulatory sequences or its coding sequences, thereby resulting in transcription of mRNAs which encode proteins truncated in either the N- or C-terminal regions. The frequency of insertional mutations is of course related to the number of integration events and the size of the target sequence.