The mechanism of genome replication and transcription in bunyaviruses

• Published in: PLoS pathogens Vol. 19; no. 1; p. e1011060
• Main Authors: Malet, Hélène, Williams, Harry M, Cusack, Stephen, Rosenthal, Maria
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12.01.2023; Public Library of Science (PLoS)
• Subjects: Analysis; Biology and life sciences; Bunyaviridae; Bunyaviridae - genetics; Bunyaviridae - metabolism; Bunyaviruses; Crystallography; Development and progression; DNA replication; DNA-directed RNA polymerase; Electron microscopy; Enzymes; Epidemics; Fever; Genetic aspects; Genetic transcription; Genomes; Genomics; Host plants; Identification and classification; Influenza; Influenza viruses; Kenya; L protein; Life Sciences; Medicine and Health Sciences; Microscopy; Orthobunyavirus; Orthobunyavirus - genetics; Proteins; Replication; Review; RNA; RNA viruses; RNA-directed RNA polymerase; Structure; Therapeutic targets; Thrombocytopenia; Transcription; Vertebrates; Viral Proteins; Viral Proteins - genetics; Viral Proteins - metabolism; Virus Replication; Virus Replication - genetics; Viruses; France; Kenya; La Crosse Wisconsin; United States > US
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1011060

Bunyaviruses are negative sense, single-strand RNA viruses that infect a wide range of vertebrate, invertebrate and plant hosts. WHO lists three bunyavirus diseases as priority diseases requiring urgent development of medical countermeasures highlighting their high epidemic potential. While the viral large (L) protein containing the RNA-dependent RNA polymerase is a key enzyme in the viral replication cycle and therefore a suitable drug target, our knowledge on the structure and activities of this multifunctional protein has, until recently, been very limited. However, in the last few years, facilitated by the technical advances in the field of cryogenic electron microscopy, many structures of bunyavirus L proteins have been solved. These structures significantly enhance our mechanistic understanding of bunyavirus genome replication and transcription processes and highlight differences and commonalities between the L proteins of different bunyavirus families. Here, we provide a review of our current understanding of genome replication and transcription in bunyaviruses with a focus on the viral L protein. Further, we compare within bunyaviruses and with the related influenza virus polymerase complex and highlight open questions.