Rift Valley fever virus NSS gene expression correlates with a defect in nuclear mRNA export

Copeland, Anna Maria; Deusen, Nicole M. Van; Schmaljohn, Connie S.

doi:10.1016/j.virol.2015.09.003

Cited by 22 publications

(21 citation statements)

References 28 publications

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“…Copeland et al . previously showed that there is a defect in mRNA export in RVFV-infected cells, and this export defect correlates with NSs gene expression 46 . Their work demonstrated that host mRNA was localized to the nucleus of infected cells when compared to mock-infected cells, and that NSs is responsible for this phenomenon.…”

Section: Resultsmentioning

confidence: 91%

Alterations in the host transcriptome in vitro following Rift Valley fever virus infection

Pinkham

Dahal

Fuente

et al. 2017

Sci Rep

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Rift Valley fever virus (RVFV) causes major outbreaks among livestock, characterized by “abortion storms” in which spontaneous abortion occurs in almost 100% of pregnant ruminants. Humans can also become infected with mild symptoms that can progress to more severe symptoms, such as hepatitis, encephalitis, and hemorrhagic fever. The goal of this study was to use RNA-sequencing (RNA-seq) to analyze the host transcriptome in response to RVFV infection. G2/M DNA damage checkpoint, ATM signaling, mitochondrial dysfunction, regulation of the antiviral response, and integrin-linked kinase (ILK) signaling were among the top altered canonical pathways with both the attenuated MP12 strain and the fully virulent ZH548 strain. Although several mRNA transcripts were highly upregulated, an increase at the protein level was not observed for the selected genes, which was at least partially due to the NSs dependent block in mRNA export. Inhibition of ILK signaling, which is involved in cell motility and cytoskeletal reorganization, resulted in reduced RVFV replication, indicating that this pathway is important for viral replication. Overall, this is the first global transcriptomic analysis of the human host response following RVFV infection, which could give insight into novel host responses that have not yet been explored.

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Section: Resultsmentioning

confidence: 91%

Alterations in the host transcriptome in vitro following Rift Valley fever virus infection

Pinkham

Dahal

Fuente

et al. 2017

Sci Rep

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“…The interaction with TFIIH-p62 thereby depends on a ΩXaV motif (where Ω: aromatic, X: any, a: acidic, V: valine) located in the C-terminal region of RVFV NSs [ 124 ]. Moreover, a nuclear mRNA export block was observed in RVFV NSs-expressing cells [ 125 ]. In contrast to these broadly-acting host cell shutoff mechanisms, RVFV NSs was also reported to specifically inhibit IFN induction by recruiting a transcriptional suppressor complex containing Sin3A associated protein 30 (SAP30) to the IFN-β promoter [ 126 ].…”

Section: Viral Countermeasuresmentioning

confidence: 99%

Phleboviruses and the Type I Interferon Response

Wuerth

Weber

2016

Viruses

104

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The genus Phlebovirus of the family Bunyaviridae contains a number of emerging virus species which pose a threat to both human and animal health. Most prominent members include Rift Valley fever virus (RVFV), sandfly fever Naples virus (SFNV), sandfly fever Sicilian virus (SFSV), Toscana virus (TOSV), Punta Toro virus (PTV), and the two new members severe fever with thrombocytopenia syndrome virus (SFTSV) and Heartland virus (HRTV). The nonstructural protein NSs is well established as the main phleboviral virulence factor in the mammalian host. NSs acts as antagonist of the antiviral type I interferon (IFN) system. Recent progress in the elucidation of the molecular functions of a growing list of NSs proteins highlights the astonishing variety of strategies employed by phleboviruses to evade the IFN system.

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“…Within the Phenuiviridae family, the IFN antagonistic functions of the non-structural (NSs) proteins of Rift Valley Fever Virus (RVFV) and Uukuniemi virus (UUKV) have been extensively studied and reviewed [97][98][99]. RVFV NSs localizes to the nucleus where it directly inhibits IFN-β promoter activity, and directly prevents the export of host mRNA to the cytoplasm [100,101]. UUKV has not been shown to cause disease in humans; UUKV NSs has weak IFN antagonism activity through its interaction with MAVS [98,99].…”

Section: Innate Immune Evasion By Interferon-antagonistic Function Ofmentioning

confidence: 99%

Immune Modulation and Immune-Mediated Pathogenesis of Emerging Tickborne Banyangviruses

2019

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In the last decade, the emergence of several, novel tickborne viruses have caused significant disease in humans. Of interest are the tickborne banyangviruses: Severe fever with thrombocytopenia syndrome virus (SFTSV), Heartland virus (HRTV), and Guertu virus (GTV). SFTSV and HRTV infection in humans cause viral hemorrhagic fever-like disease leading to mortality rates ranging from 6–30% of the cases. The systemic inflammatory response syndrome (SIRS) associated with SFTSV infection is hypothesized to contribute significantly to pathology seen in patients. Despite the severe disease caused by HRTV and SFTSV, there are no approved therapeutics or vaccines. Investigation of the immune response during and following infection is critical to the generation of fully protective vaccines and/or supportive treatments, and overall understanding of viral immune evasion mechanisms may aid in the development of a new class of therapeutics.

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Rift Valley fever virus NSS gene expression correlates with a defect in nuclear mRNA export

Cited by 22 publications

References 28 publications

Alterations in the host transcriptome in vitro following Rift Valley fever virus infection

Alterations in the host transcriptome in vitro following Rift Valley fever virus infection

Phleboviruses and the Type I Interferon Response

Immune Modulation and Immune-Mediated Pathogenesis of Emerging Tickborne Banyangviruses

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