Which viruses have RNA-dependent RNA polymerase (RdRp) without proofreading capabilities?

From the Guidelines

RNA viruses such as influenza, hepatitis C, poliovirus, rhinovirus, and coronaviruses (except SARS-CoV-2) have RNA-dependent RNA polymerase (RdRp) without proofreading capabilities. These viruses rely on RdRp to replicate their RNA genomes, but unlike DNA polymerases, most RdRps lack the ability to detect and correct errors during replication. This absence of proofreading leads to high mutation rates, estimated at approximately 10^-4 to 10^-5 errors per nucleotide per replication cycle, which is significantly higher than in DNA viruses 1. The lack of proofreading contributes to the rapid evolution of these viruses, allowing them to quickly adapt to selective pressures such as host immune responses and antiviral medications. Notably, SARS-CoV-2 and other coronaviruses in the Coronaviridae family are exceptions, as they possess an exoribonuclease (ExoN) domain in their nsp14 protein that provides some proofreading function, resulting in a lower mutation rate compared to other RNA viruses 1.

Some key points to consider:

• The high error rate of RdRp in RNA viruses leads to the creation of quasispecies, which are populations of genetically related viruses that can evolve rapidly in response to selective pressures 1.
• The lack of proofreading in RdRp also makes these viruses more susceptible to antiviral medications that target the RdRp, such as favipiravir 1.
• The ExoN domain in SARS-CoV-2 and other coronaviruses provides some proofreading function, which may contribute to their relatively lower mutation rates compared to other RNA viruses 1.

Overall, the absence of proofreading in RdRp is a key factor in the evolution and adaptation of RNA viruses, and understanding this mechanism is crucial for the development of effective antiviral therapies.

From the Research

Viruses with RNA-Dependent RNA Polymerase without Proofreading

• The RNA-dependent RNA polymerase (RdRp) is a crucial enzyme for the replication and transcription of RNA viruses, and its low fidelity and lack of proofreading capabilities allow for high mutation frequencies and rapid adaptation to changing environments 2.
• RNA viruses, including those from the Picornaviridae family, typically encode their own RdRp, which is essential for their life cycle and adaptive potential 2, 3.
• The absence of proofreading and excision activities within the RdRPs of RNA viruses results in high mutation frequencies, allowing them to rapidly adapt to changing environments 2.
• Examples of RNA viruses with RdRp without proofreading capabilities include:
  • Picornaviruses, such as poliovirus and rhinovirus 2
  • Other RNA viruses, including coronaviruses, such as SARS-CoV-2 4
• The structural and functional aspects of RdRPs have been studied in various RNA virus families, including Group III, IV, and V viruses, providing insights into their mechanism of action and potential targets for antiviral therapy 5, 3.