A genus-specific nsp12 region impacts polymerase assembly in Alphacoronavirus and Gammacoronavirus

J Biol Chem. 2024 Nov;300(11):107802. doi: 10.1016/j.jbc.2024.107802. Epub 2024 Sep 21.

Abstract

Coronavirus relevancy for human health has surged over the past 20 years as they have a propensity for spillover into humans from animal reservoirs resulting in pandemics such as COVID-19. The diversity within the Coronavirinae subfamily and high infection frequency in animal species worldwide creates a looming threat that calls for research across all genera within the Coronavirinae subfamily. We sought to contribute to the limited structural knowledge within the Gammacoronavirus genera and determined the structure of the viral core replication-transcription complex (RTC) from infectious bronchitis virus using single-particle cryo-electron microscopy. Comparison between our infectious bronchitis virus structure with published RTC structures from other Coronavirinae genera reveals structural differences across genera. Using in vitro biochemical assays, we characterized these differences and revealed their differing involvement in core RTC formation across different genera. Our findings highlight the value of cross-genera Coronavirinae studies, as they show genera-specific features in coronavirus genome replication. A broader knowledge of coronavirus replication will better prepare us for future coronavirus spillovers.

Keywords: RNA virus; protein complex; structural biology; viral polymerase; viral transcription.

MeSH terms

  • Alphacoronavirus / genetics
  • Alphacoronavirus / metabolism
  • Animals
  • Coronavirus / genetics
  • Coronavirus RNA-Dependent RNA Polymerase
  • Cryoelectron Microscopy
  • Humans
  • Viral Nonstructural Proteins* / chemistry
  • Viral Nonstructural Proteins* / genetics
  • Viral Nonstructural Proteins* / metabolism
  • Virus Replication

Substances

  • Viral Nonstructural Proteins
  • NSP12 protein, SARS-CoV-2
  • Coronavirus RNA-Dependent RNA Polymerase