The mechanism of genome replication and transcription in bunyaviruses

Abstract

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.

A natural variation in the RNA polymerase of severe fever with thrombocytopenia syndrome virus enhances viral replication and in vivo virulence

“…The linker, which connects the endonuclease to the influenza PA‐C‐like domain, wraps around the RdRp core and contributes to maintaining structural integrity and flexibility. While the endonuclease is required for priming the viral transcription via cap‐snatching mechanism, the CBD of PB2‐like subunit captures nascent host pre‐mRNA 37,38 . Conformational changes of both the linker and the endonuclease were suggested for the further elongation process 28 .…”

“…While the endonuclease is required for priming the viral transcription via cap-snatching mechanism, the CBD of PB2like subunit captures nascent host pre-mRNA. 37,38 Conformational changes of both the linker and the endonuclease were suggested for the further elongation process. 28 The negatively charged surface of the linker region may be involved in interactions with other proteins or RNA molecules that are important for viral transcription initiation.…”

The La Crosse virus class II fusion glycoproteinijloop contributes to infectivity and cholesterol-dependent entry

“…La Crosse virus (LACV) is a member of the orthobunyavirus genus and is an enveloped segmented negative-strand RNA virus that contains a tripartite genome consisting of S, M, and L segments (6,7). The S segment encodes for the nucleoprotein (N) and NSs protein (4,8), the M segment encodes for the viral glycoproteins Gn and Gc (7,9) and nonstructural protein NSm, and the L segment encodes for the viral RNA dependent RNA polymerase (4).…”

“…The Bunyavirales order includes a number of significant human pathogens such as Rift Valley fever virus, La Crosse virus, Oropouche virus, and Crimean Congo hemorrhagic fever virus (4, 5). La Crosse virus (LACV) is a member of the orthobunyavirus genus and is an enveloped segmented negative-strand RNA virus that contains a tripartite genome consisting of S, M, and L segments (6, 7).…”

“…La Crosse virus (LACV) is a member of the orthobunyavirus genus and is an enveloped segmented negative-strand RNA virus that contains a tripartite genome consisting of S, M, and L segments (6, 7). The S segment encodes for the nucleoprotein (N) and NSs protein (4, 8), the M segment encodes for the viral glycoproteins Gn and Gc (7, 9) and nonstructural protein NSm, and the L segment encodes for the viral RNA dependent RNA polymerase (4). LACV is transmitted by the Aedes species of mosquito (10, 11) and can cause severe encephalitis, as it is the most common cause of pediatric neuroinvasive arboviral disease in children in the United States (12–15).…”