Selective Translation of Viral mRNA in Productively-Infected Cells

SELECTIVE TRANSLATION OF VIRAL mRNA IN PRODUCTIVELY-INFECTED CELLS 

Such a profound inhibition of cellular protein synthesis is not an uncommon feature of virus infections of mammalian cells. Several lines of research have recently converged to demonstrate that adenoviruses, like certain other viruses that inhibit cellular protein synthesis, such as the picornaviruses poliomyelitis virus and encephal-omyocarditis virus, have evolved a mechanism to permit the selective translation of viral mRNA species. Although both adenoviruses and picornaviruses can efficiently redirect the translational machinery of their host cells, the actual molecular mechanisms employed appear to be quite distinct. 

The first evidence for control of translation in adenovirus-infected cells came when mRNA isolated from infected cells harvested during the late phase was translated in heterologous, cell-free systems, usually derived from reticulocyte lysates such mRNA preparations direct the synthesis of quite substantial quantities of cellular proteins in addition to large amounts of viral structural proteins (see, for example, Anderson et ai, 1974 Lewis et ai, 1975 Paterson et ai, 1977). The mRNA was prepared from cells collected at a time 

Adenovirus infection of human cells disrupts the entry into the cytoplasm of newly-synthesized cellular mRNA sequences (see Sec- 

Each of these four mRNA species is stable in uninfected HeLa cells, with a half-life of at least several hours (Babich et al., 1983). Their high concentration in the cytoplasm, despite the inhibition of appearance in the cytoplasm of newly-synthesized RNA complementary to the four clones (Babich et al., 1983) is, therefore, not surprising and is in line with arguments given in the previous paragraph. The same result was obtained when the steady-state levels of actin mRNA in uninfected and infected cells were examined (Babich et al., 1983) Moreover, actin mRNA extracted 15 hr after infection was translated efficiently in a reticulocyte lysate. These results establish beyond any reasonable doubt that the host cells translational machinery becomes modified by the late phase of adenovirus infection such that only viral mRNA species can be recognized. 

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