Coronavirus Replication and Interaction with Host
Luis Enjuanes, Isabel Sola, Sonia Zúñiga and Fernando Almazán
from: Animal Viruses: Molecular Biology (Edited by: Thomas C. Mettenleiter and Francisco Sobrino). Caister Academic Press, U.K. (2008)
Coronavirus (CoV) genome replication takes place in the cytoplasm in a membrane-protected microenvironment, and starts with the translation of the genome to produce the viral replicase. CoV transcription involves a discontinuous RNA synthesis (template switch) during the extension of a negative copy of the subgenomic mRNAs. The requirement for basepairing during transcription has been formally demonstrated in arteriviruses and CoVs. CoV N protein is required for coronavirus RNA synthesis, and has RNA chaperone activity that may be involved in template switch. Both viral and cellular proteins are required for replication and transcription, and the role of selected proteins will be addressed. CoVs initiate translation by cap-dependent and capindependent mechanisms. Cell macromolecular synthesis may be controlled after CoV infection by locating some virus proteins in the host cell nucleus. Infection by different coronaviruses cause in the host alteration in the transcription and translation patterns, in the cell cycle, the cytoskeleton, apoptosis and coagulation pathways, inflammation, and immune and stress responses. The balance between genes up- and down-regulated could explain the pathogenesis caused by these viruses. Specific aspects of CoV-host interaction are reviewed in this chapter. Coronavirus expression systems based on single genome constructed by targeted recombination, or by using infectious cDNAs, have been developed. The possibility of expressing different genes under the control of transcription regulating sequences (TRSs) with programmable strength, and engineering tissue and species tropism indicates that CoV vectors are flexible. CoV based vectors have emerged with high potential vaccine development and, possibly, for gene therapy read more ...