La Crosse Virus Nonstructural Protein NSs Counteracts the Effects of Short Interfering RNA

Soldan, Samantha S.; Plassmeyer, Matthew L.; Matukonis, Meghan K.; González‐Scarano, Francisco

doi:10.1128/jvi.79.1.234-244.2005

Cited by 85 publications

(70 citation statements)

References 65 publications

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“…This suppressive function appears unrelated to a viral suppressor or possible activation of an interferon response by stable expression of the siRNA (Bridge et al, 2003;Sledz et al, 2003), nor to RNA editing (Scadden and Smith, 2001;Knight and Bass, 2002;Yang et al, 2005). While we are preparing our manuscript for publication, other groups also reported suppression of siRNA or miRNA function by viral suppressors in mammalian cells with medically important RNA or DNA virus infections (Lu and Cullen, 2004;Lecellier et al, 2005;Soldan et al, 2005).…”

Section: Discussionmentioning

confidence: 92%

Short-term induction and long-term suppression of HPV16 oncogene silencing by RNA interference in cervical cancer cells

et al. 2005

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RNA interference-mediated gene silencing has the potential to block gene expression. A synthetic double-stranded small interfering RNA (siRNA) based on a sequence motif of 21 nucleotides from human papillomavirus 16 (HPV16) E6E7 bicistronic RNA was found to be a potent siRNA that suppresses expression of both the E6 and E7 oncogenes in HPV16þ CaSki and SiHa cells. When stably expressed as a short hairpin RNA in these cells, however, siRNA silencing of E6 and E7 expression was efficient only at early cell passages, but became inefficient with increased cell passages despite the continued expression of the siRNA at the same level. The loss of the siRNA function was duplicable in stable p53 siRNA cells, but not in stable lamin A/C siRNA cells, suggesting that it is gene selective. The cells resistant to siRNA function retained normal siRNA processing, duplex unwinding and degradation of the unwound sense strand and RNA-induced silencing complex formation, suggesting that loss of the siRNA function occurred at a later step. Surprisingly, the siRNA-resistant cells were found to express notably a cytoplasmic protein of B50 kDa that specifically and characteristically interacted with the unwound, antisense strand E7 siRNA. Altogether, our data indicate that a potent siRNA targeting to an essential or regulatory gene might induce a cell to develop siRNA-suppressive function.

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Section: Discussionmentioning

confidence: 92%

Short-term induction and long-term suppression of HPV16 oncogene silencing by RNA interference in cervical cancer cells

et al. 2005

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“…This could perhaps be the result of viral evasion or antagonism strategies utilized by the live virus. It has been shown that some other members of the family Bunyviridae encode a nonstructural protein, NSs, which inhibits cellular IFN responses (5,39).…”

Section: Vol 79 2005 Hantavirus Innate Immune Responses 15013mentioning

confidence: 99%

Induction of Innate Immune Response Genes by Sin Nombre Hantavirus Does Not Require Viral Replication

Prescott¹,

Ye²,

Sen

et al. 2005

J Virol

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Maladaptive immune responses are considered to be important factors in the pathogenesis of the two diseases caused by hantaviruses, hemorrhagic fever with renal syndrome and hantavirus cardiopulmonary syndrome (HCPS). While the intensity of adaptive antiviral T-cell responses seems to correlate with the severity of HCPS, there is increasing evidence that innate antiviral responses by endothelial cells, the native targets for hantavirus infection in vivo, are induced within hours of exposure to infectious hantaviruses. To investigate early events in the innate response to Sin Nombre virus (SNV), the principal etiologic agent of HCPS in North America, we treated human endothelial cells with live virus, or virus subjected to inactivation by UV irradiation at minimal doses required to inhibit replication, and assayed host expression of interferonstimulated genes (ISG) by microarray and reverse transcription-PCR. We show herein that a variety of ISG are induced between 4 and 24 h after exposure to both live and killed virus. The levels of such induction at early time points (before 24 h) were generally higher in cells treated with SNV particles that had been killed by exposure to UV irradiation. Additionally, SNV exposed to increasing doses of UV irradiation induced ISG better than live virus despite increased disruption of viral RNA integrity. However, SNV replication was required for continued ISG overexpression by 3 days posttreatment. These results suggest that hantavirus particles may themselves be capable of early induction of ISG and that ongoing production of viral particles during infection could contribute to the pathogenic process.

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“…Also human-infecting viruses encode proteins that can act as suppressors of RNA silencing. The NS1 protein of Influenza virus A is active in insect cells as well as in plants (Bucher et al 2004;Delgadillo et al 2004;Li et al 2004) and the NSs protein of La Crosse virus (LACV) shows RNA silencing inhibition in human cells (Soldan et al 2005).…”

Section: Introductionmentioning

confidence: 99%

The NS3 protein of Rice hoja blanca tenuivirus suppresses RNA silencing in plant and insect hosts by efficiently binding both siRNAs and miRNAs

Hemmes¹,

Lakatos²,

Goldbach³

et al. 2007

RNA

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RNA silencing plays a key role in antiviral defense as well as in developmental processes in plants and insects. Negative strand RNA viruses such as the plant virus Rice hoja blanca tenuivirus (RHBV) replicate in plants and in their insect transmission vector. Like most plant-infecting viruses, RHBV encodes an RNA silencing suppressor, the NS3 protein, and here it is demonstrated that this protein is capable of suppressing RNA silencing in both plants and insect cells. Biochemical analyses showed that NS3 efficiently binds siRNA as well as miRNA molecules. Binding of NS3 is greatly influenced by the size of small RNA molecules, as 21 nucleotide (nt) siRNA molecules are bound > 100 times more efficiently than 26 nt species. Competition assays suggest that the activity of NS3 is based on binding to siRNAs prior to strand separation during the assembly of the RNAinduced silencing complex. In addition, NS3 has a high affinity for miRNA/miRNA* duplexes, indicating that its activity might also interfere with miRNA-regulated gene expression in both insects and plants.

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La Crosse Virus Nonstructural Protein NSs Counteracts the Effects of Short Interfering RNA

Cited by 85 publications

References 65 publications

Short-term induction and long-term suppression of HPV16 oncogene silencing by RNA interference in cervical cancer cells

Short-term induction and long-term suppression of HPV16 oncogene silencing by RNA interference in cervical cancer cells

Induction of Innate Immune Response Genes by Sin Nombre Hantavirus Does Not Require Viral Replication

The NS3 protein of Rice hoja blanca tenuivirus suppresses RNA silencing in plant and insect hosts by efficiently binding both siRNAs and miRNAs

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