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