Induced Shut-Off of Host Translation

Many cytopathogenic viruses induce a decline in the rate of host mRNA translation upon infection. Since this shut-off of host translation is accompanied by extensive synthesis of viral protein, and since the decline in host protein synthesis is not concomitant with degradation or inactivation of host mRNA, it is clear that translational control mechanisms are involved in this phenomenon. A number of explanations have been invoked to explain shut-off by various viruses. Here, a few of these will be examined that are related directly to the material already reviewed above, but for a more extensive treatment, surveys by Koch et al. (1982) and elsewhere in this volume should be consulted. 

A mechanism that may be restricted more specifically to certain viruses is the inactivation of cap-binding proteins accompanying, for example, the shut-off of host protein synthesis by poliovirus (see Chapter by E. Ehrenfeld in this volume). Lee and Sonenberg (1982) have demonstrated that the ability of five polypeptides, associated with the CBP II complex, to be crosslinked to the cap is reduced in extracts of poliovirus-infected cells. This reduction correlates with 

A related change occurs during the late stages of replication of reovirus in L cells. The early reovirus mRNA is capped and is translated in competition with host mRNA. Late in infection, however, the viral mRNA is uncapped, and it cannot be translated in extracts of uninfected cells, even though it is an efficient template for translation in extracts of infected cells (Skup et al., 1981). Apparently, reovirus induces a gradual modification in the cap-binding proteins, such that late in infection, translation of host mRNA and early viral mRNA comes to a halt, permitting only the translation of uncapped viral mRNA. 

Several host-virus interactions at the level of translational control may involve eIF-2. The ability of a strong viral RNA template, such as mengovirus RNA, to out-compete host mRNA for eIF-2 (Rosen et al., 1982) will lead to the selective translation of viral mRNA concomitant with a displacement of host mRNA from the ribosomes. 

Even though in mengovirus-infected cells, the physical intactness of host mRNA as a whole does not change perceptibly (Colby et al., 1974), host mRNA, once displaced, may become more prone to limited nuclease attack at sites essential for translation. 

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This section is devoted to several cases of translational control where specific initiation factor(s), if involved, have not yet been identified, or where more than one mechanism of control is activated, as in the case of virus-induced shut-off of host translation. 

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