Journal Article

Orthobunyaviruses: recent genetic and structural insights

Elliott, Richard M.

2014

Overview

Key Points Orthobunyaviruses are arthropod-transmitted viruses that are characterized by a tripartite, negative-sense RNA genome. Some viruses in this family are associated with diseases in humans (such as fever and encephalitis) and domesticated animals (including abortion and teratogenic effects in offspring). Schmallenberg virus, which is a recently emerged member of the family, caused a disease outbreak in domesticated animals in Europe in 2012–2013. Viral replication occurs in the cytoplasm of infected cells and viruses mature by budding in the Golgi complex. Although infection of mammalian cells usually results in cell death, replication in arthropod vector cells is not cytopathic and these cells become persistently infected. Viral mRNA synthesis is primed by capped oligonucleotides that are derived from host cell mRNAs in a process that is known as cap snatching. The endonuclease activity that is responsible for generating the primers is contained in the amino-terminal domain of the viral RNA-dependent RNA polymerase protein. The three-dimensional structure of the viral N (nucleocapsid) protein shows that it forms a tetramer that contains a novel fold with a central, positively charged groove that binds to the viral RNA. The viral non-structural protein NSs is the major virulence factor and antagonizes the host innate immune response by causing global inhibition of RNA polymerase II-mediated transcription. Possession of a segmented genome enables orthobunyaviruses to evolve rapidly by segment reassortment during mixed infections. Reassortment occurs widely in nature and reassortant viruses can have dramatically altered properties, such as increased virulence. Little is known about the burden of orthobunyavirus disease and there is a need for improved global surveillance to monitor orthobunyavirus activity. Orthobunyaviruses are transmitted by arthropod vectors and can infect humans, animals and crops. In this Review, Elliott describes recent genetic and structural advances that have revealed important insights into the composition of orthobunyavirus virions, viral transcription and replication, and viral interactions with the host innate immune response. Orthobunyaviruses, which have small, tripartite, negative-sense RNA genomes and structurally simple virions composed of just four proteins, can have devastating effects on human health and well-being, either by causing disease in humans or by causing disease in livestock and crops. In this Review, I describe the recent genetic and structural advances that have revealed important insights into the composition of orthobunyavirus virions, viral transcription and replication and viral interactions with the host innate immune response. Lastly, I highlight outstanding questions and areas of future research.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/326/596/2148 / 631/326/596/2555 / 631/326/596/2557 / 631/326/596/2563 / Animal diseases / Animals / Arthropods / Bunyaviridae Infections - epidemiology / Bunyaviridae Infections - pathology / Bunyaviridae Infections - veterinary / Bunyaviridae Infections - virology / Cell death / Chemical synthesis / Congenital diseases / Cytoplasm / Disease transmission / DNA-directed RNA polymerase / Domestic animals / Domestication / Encephalitis / Endonuclease / Fever / Genetic aspects / Genetic research / Genomes / Golgi cells / Grooves / Host-Pathogen Interactions / Humans / Immune response / Immune system / Infectious Diseases / Innate immunity / Life Sciences / Livestock / Mammalian cells / Medical Microbiology / Medical research / Microbiology / Mosquitoes / Nucleocapsids / Offspring / Oligonucleotides / Orthobunyavirus / Orthobunyavirus - genetics / Orthobunyavirus - immunology / Orthobunyavirus - physiology / Parasitology / Protein biosynthesis / Protein folding / Protein structure / Proteins / Replication / review-article / Ribonucleic acid / RNA / RNA polymerase / RNA polymerase II / RNA viruses / RNA-directed RNA polymerase / Teratogenicity / Transcription / Transcription, Genetic / Vectors / Virions / Virology / Virulence / Virulence factors / Virus Replication / Viruses