Differential synthesis of mammalian type C viral gene products in infected cells

Radioimmunological techniques were applied to the quantitation of the translational products of the gag, pol, and env genes of mammalian type C viruses. Analysis of the viral proteins associated with simian sarcoma associated virus (SSAV) and SSAV-infected cells revealed in each that the level of reverse transcriptase was less than 1% of that of the major viral structural protein, p30. The rate of intracellular degradation of reverse transcriptase in SSAV infected cells was found to be no greater than that of several viral structural proteins, indicating that the lower levels of viral enzyme resulted from its decreased synthesis. By screening individual cells infected at limiting SSAV dilution, it was possible to isolate a clone (clone 16), which demonstrated levels of viral p12, p30, and gp70 similar to those found in wild type SSAV infected cells, and which released noninfectious virions in large quantity. The noninfectious virions and clone 16 cells were shown to lack immunologically or enzymologically detectable reverse transcriptase. With serial passage of clone 16 cells, reverse transcriptase activity became spontaneously detectable in tissue culture fluids, concomitant with the appearance of infectious virus. The reverse transcriptase associated with this virus was indistinguishable from SSAV polymerase, indicating that the genetic alteration restricting SSAV pol gene expression in clone 16 cells was reversible. These results further demonstrate the strict requirement of reverse transcriptase for establishment of type C virus infection. Possible mechanisms to account for the patterns of type C viral gene expression detected in SSAV infected cells are discussed.