Viral and Cellular Proteins Involved in Coronavirus Replication

Abstract

As the largest RNA virus, coronavirus replication employs complex mechanisms and involves various viral and cellular proteins. The first open reading frame of the coronavirus genome encodes a large polyprotein, which is processed into a number of viral proteins required for viral replication directly or indirectly. These proteins include the RNA-dependent RNA polymerase (RdRp), RNA helicase, proteases, metal-binding proteins, and a number of other proteins of unknown function. Genetic studies suggest that most of these proteins are involved in viral RNA replication. In addition to viral proteins, several cellular proteins, such as heterogeneous nuclear ribonucleoprotein (hnRNP) A1, polypyrimidine-tract-binding (PTB) protein, poly(A)-binding protein (PABP), and mitochondrial aconitase (m-aconitase), have been identified to interact with the critical cis-acting elements of coronavirus replication. Like many other RNA viruses, coronavirus may subvert these cellu-lar proteins from cellular RNA processing or translation machineries to play a role in viral replication. Viral and Cellular Proteins Involved in Coronavirus Replication 97

Polypyrimidine tract-binding protein is relocated to the cytoplasm and is required during dengue virus infection in Vero cells

“…Although the specific functions of all of these cellular proteins is unclear, in other viruses it has been described in detail that they participate in RNA stability, as well as in translation and replication of the viral genome (Bushell & Sarnow, 2002;Shi & Lai, 2005). PTB, a 57 kDa protein (also called hnRNP1), is a member of the hnRNP family and contains four RNA-recognition motifs.…”

“…Consistent with their putative role in viral replication, both NS3 and NS5 exist as a complex in DENV-infected cells (Kapoor et al, 1995) and interact with the 39-and 59UTR of Japanese encephalitis virus and DENV RNA, respectively (Chen et al, 1997;Filomatori et al, 2006;Lodeiro et al, 2009;Luo et al, 2008). Additionally, some sequences present in the 39-and 59UTR are able to interact with cellular proteins such as La, polypyrimidine tract-binding protein (PTB), translation elongation factor 1a, Y box-binding protein 1, heterogeneous nuclear ribonucleoproteins (hnRNPs) A1, A2/B2 and Q, protein disulfide isomerase, poly(A)-binding protein (PABP) and calreticulin (De Nova-Ocampo et al, 2002;García-Montalvo et al, 2004;Paranjape & Harris, 2007;Polacek et al, 2009;Yocupicio-Monroy et al, 2003.Although the specific functions of all of these cellular proteins is unclear, in other viruses it has been described in detail that they participate in RNA stability, as well as in translation and replication of the viral genome (Bushell & Sarnow, 2002;Shi & Lai, 2005). PTB, a 57 kDa protein (also called hnRNP1), is a member of the hnRNP family and contains four RNA-recognition motifs.…”

A Key Role for Heat Shock Protein 70 in the Localization and Insertion of Tombusvirus Replication Proteins to Intracellular Membranes

“…Using a gene-silencing approach and quercetin as a chemical inhibitor to downregulate Hsp70 levels, we also confirm the significance of cytosolic Hsp70 in the replication of TBSV and other plant viruses in a plant host. Taken together, our results suggest that cytosolic Hsp70 plays multiple roles in TBSV replication, such as affecting the subcellular localization and membrane insertion of the viral replication proteins as well as the assembly of the viral replicase.Plus-stranded RNA [(ϩ)RNA] viruses replicate efficiently in host cells by assembling their own replicase complexes, consisting of virus-and host-encoded proteins, the viral RNA, and host membranes (1,2,10,33,34,36,41,54,56,58). The replication of (ϩ)RNA viruses takes place on the cytosolic surfaces of various cellular organelles, such as the endoplasmic reticulum (ER) and mitochondria, whereas some viruses actively induce the formation of novel cytoplasmic vesicular compartments (12,16,23,24,31,53,54).…”

Authentic Replication and Recombination of Tomato Bushy Stunt Virus RNA in a Cell-Free Extract from Yeast

“…Then, the (Ϫ)RNA intermediate is used by the viral replicase to synthesize an excess amount of new (ϩ)RNA progeny, which are released from the site of replication to the cytosol (1, 24). To understand the mechanism of (ϩ)RNA virus replication, several model RNA viruses, including plant viruses, have been exploited in this intensively studied area in recent years (1,3,19,39,44).Assembling the viral replicase complex on the cytosolic surfaces of intracellular membranes is a poorly understood process (39). The viral replicase consists of virally encoded RNAdependent RNA polymerase (RdRp) and viral auxiliary replication proteins as well as co-opted host proteins, whose contribution to the viral replication process is the least understood.…”