Programmed –1 Ribosomal Frameshifting in SARS Coronavirus

In coronaviruses such as the SARS coronavirus (SARS-CoV), programmed −1 ribosomal frameshifting (−1 PRF) is used to direct the synthesis of immediate early proteins, e.g., RNA-dependent RNA polymerase (RDRP) and proteases, that are thought to prepare the infected cell for takeover by the virus. Unlike other RNA viruses which make their structural proteins first, this class of proteins is synthesized after −1 PRF, from subgenomic mRNAs produced subsequent to production of RDRP. Also unique among the coronaviruses is the inclusion of mRNA structural elements that do not appear to be essential for frameshifting. Understanding the differences between –1 PRF signals from coronaviruses and other viruses will enhance our understanding of –1 PRF in general, and will be instructive in designing new classes of antiviral therapeutics. In this chapter we summarize current knowledge and add additional insight to the function of the programmed –1 ribosomal frameshift signal present in the SARS-associated coronavirus.