Orthobunyaviruses and innate immunity induction: alieNSs vs. PredatoRRs

Schoen, Andreas; Weber, Friedemann

doi:10.1016/j.ejcb.2015.06.001

Cited by 10 publications

(12 citation statements)

References 107 publications

(130 reference statements)

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“…26,27 The NSs protein has been detected in most orthobunyaviruses that infect vertebrates and is known to be an important virulence factor. [28][29][30][31] Because infection with Patois serogroup viruses has not yet been associated with human illness, it would be interesting to determine whether the NSs of these viruses have similar virulence properties as those described for other orthobunyaviruses.…”

Section: Discussionmentioning

confidence: 99%

Genetic Characterization of the Patois Serogroup (Genus Orthobunyavirus; Family Peribunyaviridae) and Evidence That Estero Real Virus is a Member of the Genus Orthonairovirus

Aguilar

Souza

Silvas

et al. 2018

The American Journal of Tropical Medicine and Hygiene

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Estero Real virus (ERV) was isolated in 1980 from ticks collected in El Estero Real, Sancti Spiritus, Cuba. Antigenic characterization of the isolate based on serological methods found a relationship with Abras and Zegla viruses and, consequently, the virus was classified taxonomically within the Patois serogroup. Given the fact that genetic characterization of Patois serogroup viruses has not yet been reported and that ERV is the only virus within the Patois serogroup isolated from ticks, we recently conducted nearly complete genome sequencing in an attempt to gain further insight into the genetic relationship of ERV with other Patois serogroup viruses and members of family ( order). With the exception of ERV, our sequencing and phylogenetic studies revealed the close relationship of the Patois serogroup viruses to each other, forming a clear divergent clade from other members of the genus ( family). Notably, our analysis also revealed that ERV forms a monophyletic clade that is closely related to species of the genus ( family) in all the genome segments. In light of these findings, we believe that the taxonomic classification of ERV should be revised.

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Section: Discussionmentioning

confidence: 99%

Genetic Characterization of the Patois Serogroup (Genus Orthobunyavirus; Family Peribunyaviridae) and Evidence That Estero Real Virus is a Member of the Genus Orthonairovirus

Aguilar

Souza

Silvas

et al. 2018

The American Journal of Tropical Medicine and Hygiene

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“…With the exception of Anopheles A, Anopheles B, and Tete serogroups, the orthobuyaviruses code for an NSs protein by overlapping the ORF with the NP (Mohamed et al, 2009). Bunyavirus NSs play an eminent role in inhibiting the interferon response (Ly and Ikegami, 2016;Schoen and Weber, 2015) and in plants (for tospovirus) interferes the plant antiviral RNA silencing (Hedil and Kormelink, 2016). NSm proteins instead are integral membrane proteins with an unclear general role among bunyavirus.…”

Section: Bunyavirusesmentioning

confidence: 99%

Transcription and replication mechanisms of Bunyaviridae and Arenaviridae L proteins

et al. 2017

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Bunyaviridae and Arenaviridae virus families include an important number of highly pathogenic viruses for humans. They are enveloped viruses with negative stranded RNA genomes divided into three (bunyaviruses) or two (arenaviruses) segments. Each genome segment is coated by the viral nucleoproteins (NPs) and the polymerase (L protein) to form a functional ribonucleoprotein (RNP) complex. The viral RNP provides the necessary context on which the L protein carries out the biosynthetic processes of RNA replication and gene transcription. Decades of research have provided a good understanding of the molecular processes underlying RNA synthesis, both RNA replication and gene transcription, for these two families of viruses. In this review we will provide a global view of the common features, as well as differences, of the molecular biology of Bunyaviridae and Arenaviridae. We will also describe structures of protein and protein-RNA complexes so far determined for these viral families, mainly focusing on the L protein, and discuss their implications for understanding the mechanisms of viral RNA replication and gene transcription within the architecture of viral RNPs, also taking into account the cellular context in which these processes occur. Finally, we will discuss the implications of these structural findings for the development of antiviral drugs to treat human diseases caused by members of the Bunyaviridae and Arenaviridae families.

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“…The entire multiplication cycle of bunyaviruses takes place in the cytoplasm. After entering the host cell via clathrin-mediated endocytosis (18,19) and subsequent low pH-driven membrane fusion, mRNAs are transcribed from the incoming genome RNA nucleocapsids by L RdRP ("primary transcription"). The transcription is primed by 12 to 18 nt long, 5'-capped oligonucleotides that had been cleaved from host mRNA by an endonuclease activity residing in the N terminus of L (20).…”

Section: Introductionmentioning

confidence: 99%

“…After translation of the viral proteins, the viral genome RNA (vRNA) is replicated via a positive-sense, encapsidated full-length intermediate, the copy RNA (cRNA). The newly generated vRNA nucleocapsids can give rise to more mRNAs produced by secondary transcription, or become packaged by peptidase-processed Gn/Gc on Golgi membranes and leave the cell via the exocytosis pathway (19,21,22).…”

Section: Introductionmentioning

confidence: 99%

“…For orthobunyaviruses, the S segment-encoded protein NSs is a major determinant of pathogenicity, acting as an antagonist of the antiviral type I interferon (IFN) response (19,23). IFNs are cytokines that become produced upon virus detection by host cells, and stimulate the expression of genes (ISGs) for proteins with antiviral activity (24,25).…”

Section: Introductionmentioning

confidence: 99%

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Elongin C Contributes to RNA Polymerase II Degradation by the Interferon Antagonist NSs of La Crosse Orthobunyavirus

Schoen

Lau

Verbruggen

et al. 2020

J Virol

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Mosquito-borne La Crosse virus (LACV; genus Orthobunyavirus, family Peribunyaviridae, order Bunyavirales) causes up to 100 annual cases of severe meningoencephalitis in children and young adults in the United States. A major virulence factor of LACV is the nonstructural protein NSs, which inhibits host cell mRNA synthesis to prevent the induction of antiviral type I interferons (IFN-α/β). To achieve this host transcriptional shutoff, LACV NSs drives the proteasomal degradation of RPB1, the large subunit of mammalian RNA polymerase II. Here, we show that NSs acts in a surprisingly rapid manner, as RPB1 degradation was commencing already at 1 h postinfection. The RPB1 degradation was partially dependent on the cellular E3 ubiquitin ligase subunit Elongin C. Consequently, removal of Elongin C, but also of the subunits Elongin A or B by siRNA transfection partially rescued general RNAP II transcription and IFN-beta mRNA synthesis from the blockade by NSs. In line with these results, LACV NSs was found to trigger the redistribution of Elongin C out of nucleolar speckles, which, however, is an epiphenomenon rather than part of the NSs mechanism. Our study also shows that the molecular phenotype of LACV NSs is different from RNA polymerase II inhibitors like α-amanitin or Rift Valley fever virus NSs, indicating that LACV is unique in involving the Elongin complex to shut off host transcription and IFN response. IMPORTANCE The mosquito-borne La Crosse virus (LACV; genus Orthobunyavirus, family Peribunyaviridae, order Bunyavirales) is prevalent in the United States and can cause severe childhood meningoencephalitis. Its main virulence factor, the nonstructural protein NSs, is a strong inhibitor of the antiviral type I interferon (IFN) system. NSs acts by imposing a global host mRNA synthesis shutoff, mediated by NSs-driven proteasomal degradation of the RPB1 subunit of RNA polymerase II. Here, we show that RPB1 degradation commences as early as 1 h postinfection, and identify the E3 ubiquitin ligase subunit Elongin C (and its binding partners Elongins A and B) as an NSs cofactor involved in RPB1 degradation and in suppression of global as well as IFN-related mRNA synthesis.

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Orthobunyaviruses and innate immunity induction: alieNSs vs. PredatoRRs

Cited by 10 publications

References 107 publications

Genetic Characterization of the Patois Serogroup (Genus Orthobunyavirus; Family Peribunyaviridae) and Evidence That Estero Real Virus is a Member of the Genus Orthonairovirus

Genetic Characterization of the Patois Serogroup (Genus Orthobunyavirus; Family Peribunyaviridae) and Evidence That Estero Real Virus is a Member of the Genus Orthonairovirus

Transcription and replication mechanisms of Bunyaviridae and Arenaviridae L proteins

Elongin C Contributes to RNA Polymerase II Degradation by the Interferon Antagonist NSs of La Crosse Orthobunyavirus

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