Caister Academic Press

Translational Control in Herpes Simplex Virus-infected Cells

Ian Mohr
from: Alphaherpesviruses: Molecular Virology (Edited by: Sandra K. Weller). Caister Academic Press, U.K. (2011)


Like all viruses, α-herpesviruses are completely reliant upon the protein synthesis machinery resident in their host cells. In particular, viral mRNAs must effectively compete with cellular mRNAs to engage ribosomes. To ensure high-level production of the polypeptides required for their lytic replication, multiple independent gene products expressed by the model α-herpesvirus HSV-1 effectively seize control of critical host cell translational control pathways. Surprisingly, while host protein synthesis is profoundly suppressed by global changes in mRNA metabolism, the assembly of a multi-subunit, cap-binding translation initiation factor complex required to recruit 40S subunits to mRNA is directly stimulated. This involves both inactivation of a cellular translational repressor by viral functions, and direct interaction between specific viral proteins and select cellular translation initiation factors. In addition to their dependence on cellular components required for mRNA translation, virus-encoded functions must preserve its activity by neutralizing potent host responses capable of incapacitating the translation machinery, one of which senses stress within the endoplasmic reticulum lumen and another of which functions as a host innate defense component by sensing double-stranded RNA, a molecular signature of viral infection. This chapter discusses in detail the many virus-host interactions that are presently known to control translation in cells productively infected with HSV-1 and highlights recent developments in this area read more ...
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