Integrase protein of murine leukemia viruses

The defined mapping of the MuLV integrase in previous work (10,11) has made it possible for us to design and construct molecular clones for expression of this protein in bacteria and thus easily obtain specific antisera. Our repeated inability to isolate the antigenic MuLV virion p46 protein without the use of a denaturing reagent, although preventing us from carrying out the contemplated enzymological studies, would imply that the integration function of MuLV is more stringently controlled at the virion structure level than is that of avian retroviruses. Thus, gene transfer and therapy procedures would be safer to the recipient by using the MuLV retroviral vector than the avian retroviral vector, since p46 is less likely than p32 to be aberrantly released to cause genomic damage to the cell. The apparent cytotoxity of transfection with mammalian expression vectors carrying the integrase gene is not unexpected in situations where a high level of this protein is expressed and accumulated in the nucleus. The apparently incidental emergence of neoplastic phenotypes in some stably transfected cells would cause genomic instability and gene rearrangement of the oncogenic components. This possibility is particularly noteworthy for endogenous retroviral gene elements, in which the control of integrase genemore » expression and function may not be as stringent as in the infectious MuLVs. 28 refs., 5 figs.« less