Molecular mechanisms of virus-mediated cytopathology
Lytic virus infections of animal cells usually lead to a variety of morphological and biochemical lesions that include inhibition of cellular macromolecular syntheses. These cytopathic effects vary in intensity for different virus-cell combinations and probably involve several overlapping mechanisms. Inhibition may be mediated by components of parental virions or require viral gene expression. In many infected cell systems the initiation of host protein synthesis is selectively blocked. This shut-off phenomenon can result from changes in membrane permeability that alter the intracellular ionic environment in favour of viral expression, successful competition of viral mRNAs for limited translational components, or a decrease in the level of cell mRNAs by inhibition of synthesis or nucleocytoplasmic transport. However, the early onset and rapidity of virus-induced inhibition, sometimes under non-permissive conditions, implies more direct mechanisms of translational inactivation. These include enhanced degradation of cellular mRNAs or specific modification of the translation apparatus in infected cells. A dramatic example of the latter occurs in poliovirus-infected HeLa cells in which intact, functional cellular mRNA persists but host protein synthesis is almost completely inhibited. The virus-induced defect is apparently related to inactivation of a protein factor that binds to the 5' end of m7G-capped mRNAs and is required for translation of host (capped) mRNAs but not for the expression of poliovirus RNA, which is not capped. This process and other possible molecular mechanisms of virus-mediated cytopathology are discussed.