Protein synthesis alphavirus inhibition

It is well known that overall protein synthesis of permissive vertebrate cells is inhibited by alphavirus infections (Wengler, 1980). When incorporation of radioactive amino acids into proteins is analyzed using SDS-polyacrylamide gel electrophoresis (PAGE), the decrease in host protein synthesis is concomitant with the increase in the relative amounts of virus-specific polypeptides. At the end of the exponential phase of virus growth, the majority of the newly synthesized proteins are virus specific (Pfefferkorn and Shapiro, 1974 Strauss and Strauss, 1977). In general, the rate of the inhibition of host protein synthesis depends upon the multiplicity of infection as well as the time after infection. 

For alphaviruses, Garry et al. (1979a) and Contreras and Carrasco (1979) did similar experiments with SIN virus-infected CEF cells and SF virus-infected BHK cells, respectively. In SIN virus-infected CEF cells, Garry et al. (1979a) observed that the inhibition of host protein synthesis is temporally correlated with an increase in the intracellular Na concentration and a decrease in the intracellular... 

It is important to know whether viral-specified proteins are involved in the inhibition of host protein synthesis and ts mutants have been used to try to answer this question. RNA t mutants did not inhibit cellular protein synthesis at the restrictive temperature (Atkins, 1976). Under these conditions, RNA / mutants of alphaviruses make neither viral encoded proteins nor viral RNAs (Keranen and Kaariainen, 1975 Hashimoto and Simizu, 1978). From these findings, we can conclude that initiation of viral RNA replication is necessary for inhibition of host protein synthesis and also that viral components introduced into cells by the infecting virions are not directly responsible for this inhibition. 

On the other hand, RNA t mutants of alphaviruses are known to make defective proteins or uncleaved precursors at the restrictive temperature (reviewed in Strauss and Strauss, 1980). Mutants belonging to all three complementation groups of SIN RNA /5 mutants inhibit host protein synthesis at the restrictive temperature (Atkins,... 

Inhibition of protein synthesis leads to a cessation of the appearance of newly synthesized ribosomes in the cytoplasm of eukaryotic cells (Hadjiolov and Nikolaev, 1976 Wengler, 1980). This phenomenon has not been characterized in detail, but is has been shown that synthesis and/or processing of the precursors to ribosomal RNAs is inhibited. Since alphavirus infection strongly inhibits host cell pro-... 

Infection of A. albopictus cells with alphaviruses leads to the synthesis of maximum titers of infectious virus by approximately 24 hr postinfection (acute phase). At the acute phase, up to 85% of the cells released infectious virus (Davey and Dalgarno, 1974), and the rate of synthesis of intracellular 42 S and 26 S viral RNA and structural proteins is maximal. By 48 hr postinfection, viral 26 S RNA and protein syntheses are inhibited, and the proportion of cells releasing virus is dramatically reduced (Davey and Dalgarno, 1974 Eaton, 1979). Inhibition of 42 S RNA synthesis occurs at 3 days after infection (start of chronic phase see Fig. 2). The nature of the factor(s) responsible for inhibiting viral replication in infected mosquito cells at the chronic phase is not known. The fact that large amounts of 42 S RNA are made in infected mosquito cells 48 hr after infection, at a time when viral structural protein synthesis is inhibited, suggests that the replication inhibition factor may act initially at the level of viral protein synthesis (Eaton, 1979). Eaton demonstrated that viral structural protein synthesis is inhibited before a decrease in 26 S RNA synthesis is detected in SIN-infected A. albopictus cells. Thus, the biphasic nature of alphavirus infection is also observed in the case of flavivirus infection in mosquito cells (Paul et al., 1969). 

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