Highly effective inhibition of Akabane virus replication by siRNA genes

Levin, Aviad; Kutznetova, Larisa; Kahana, Ronen; Rubinstein-Guini, Marisol; Stram, Yehuda

doi:10.1016/j.virusres.2006.02.009

Cited by 15 publications

(17 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The siS pool targets the virus S segment, which encodes the virus N protein. Treatment with this siRNA pool very efficiently reduced virus protein levels, a result consistent with previous findings in other bunyaviruses [14], [24]–[26]. The N mRNA can be detected as early as 2 h post ANDV infection, and is the first viral RNA detected during infection [27], [28].…”

Section: Discussionsupporting

confidence: 88%

Small Interfering RNA Inhibition of Andes Virus Replication

Chiang

Albariño

et al. 2014

PLoS ONE

View full text Add to dashboard Cite

Andes virus (ANDV) is the most common causative agent of hantavirus pulmonary syndrome (HPS) in the Americas, and is the only hantavirus associated with human-to-human transmission. Case fatality rates of ANDV-induced HPS are approximately 40%. There are currently no effective vaccines or antivirals against ANDV. Since HPS severity correlates with viral load, we tested small interfering RNA (siRNA) directed against ANDV genes as a potential antiviral strategy. We designed pools of 4 siRNAs targeting each of the ANDV genome segments (S, M, and L), and tested their efficacy in reducing viral replication in vitro. The siRNA pool targeting the S segment reduced viral transcription and replication in Vero-E6 cells more efficiently than those targeting the M and L segments. In contrast, siRNAs targeting the S, M, or L segment were similar in their ability to reduce viral replication in human lung microvascular endothelial cells. Importantly, these siRNAs inhibit ANDV replication even if given after infection. Taken together, our findings indicate that siRNAs targeting the ANDV genome efficiently inhibit ANDV replication, and show promise as a strategy for developing therapeutics against ANDV infection.

show abstract

Section: Discussionsupporting

confidence: 88%

Small Interfering RNA Inhibition of Andes Virus Replication

Chiang

Albariño

et al. 2014

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Furthermore, in mammalian cells La Crosse virus replication was successfully decreased by siRNAs targeting the S segment and similarly to our results, the L and M siRNAs had a much weaker effect [47]. Finally, orthobunyavirus Akabane replication was inhibited up to 99% by siRNAs directed against highly conserved regions of the nucleoprotein gene [48]. …”

Section: Discussionsupporting

confidence: 72%

Inhibition of Hazara nairovirus replication by small interfering RNAs and their combination with ribavirin

Flusin¹,

Vigne²,

Peyrefitte³

et al. 2011

Virol J

View full text Add to dashboard Cite

BackgroundThe genus Nairovirus in the family Bunyaviridae contains 34 tick-borne viruses classified into seven serogroups. Hazara virus (HAZV) belongs to the Crimean-Congo hemorrhagic fever (CCHF) serogroup that also includes CCHF virus (CCHFV) a major pathogen for humans. HAZV is an interesting model to study CCHFV due to a close serological and phylogenetical relationship and a classification which allows handling in a BSL2 laboratory. Nairoviruses are characterized by a tripartite negative-sense single stranded RNA genome (named L, M and S segments) that encode the RNA polymerase, the Gn-Gc glycoproteins and the nucleoprotein (NP), respectively. Currently, there are neither vaccines nor effective therapies for the treatment of any bunyavirus infection in humans. In this study we report, for the first time, the use of RNA interference (RNAi) as an approach to inhibit nairovirus replication.ResultsChemically synthesized siRNAs were designed to target the mRNA produced by the three genomic segments. We first demonstrated that the siRNAs targeting the NP mRNA displayed a stronger antiviral effect than those complementary to the L and M transcripts in A549 cells. We further characterized the two most efficient siRNAs showing, that the induced inhibition is specific and associated with a decrease in NP synthesis during HAZV infection. Furthermore, both siRNAs depicted an antiviral activity when used before and after HAZV infection. We next showed that HAZV was sensitive to ribavirin which is also known to inhibit CCHFV. Finally, we demonstrated the additive or synergistic antiviral effect of siRNAs used in combination with ribavirin.ConclusionsOur study highlights the interest of using RNAi (alone or in combination with ribavirin) to treat nairovirus infection. This approach has to be considered for the development of future antiviral compounds targeting CCHFV, the most pathogenic nairovirus.

show abstract

“…After reaching 70-80% confluence, cells were arrested in the cell cycle by treatment with 5 μg/ml of aphidicolin, and then incubated with 150 μM of the indicated peptide for 6 h. Cells were fixed and immunostained essentially as described previously [66] with several modifications. Briefly, after fixation cells were blocked with 5% (w/v) BSA (IgG free) (Jackson) in PBS for 60 min.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of HIV-1 integrase nuclear import and replication by a peptide bearing integrase putative nuclear localization signal

et al. 2009

Self Cite

View full text Add to dashboard Cite

BackgroundThe integrase (IN) of human immunodeficiency virus type 1 (HIV-1) has been implicated in different steps during viral replication, including nuclear import of the viral pre-integration complex. The exact mechanisms underlying the nuclear import of IN and especially the question of whether it bears a functional nuclear localization signal (NLS) remain controversial.ResultsHere, we studied the nuclear import pathway of IN by using multiple in vivo and in vitro systems. Nuclear import was not observed in an importin α temperature-sensitive yeast mutant, indicating an importin α-mediated process. Direct interaction between the full-length IN and importin α was demonstrated in vivo using bimolecular fluorescence complementation assay (BiFC). Nuclear import studies in yeast cells, with permeabilized mammalian cells, or microinjected cultured mammalian cells strongly suggest that the IN bears a NLS domain located between residues 161 and 173. A peptide bearing this sequence -NLS-IN peptide- inhibited nuclear accumulation of IN in transfected cell-cycle arrested cells. Integration of viral cDNA as well as HIV-1 replication in viral cell-cycle arrested infected cells were blocked by the NLS-IN peptide.ConclusionOur present findings support the view that nuclear import of IN occurs via the importin α pathway and is promoted by a specific NLS domain. This import could be blocked by NLS-IN peptide, resulting in inhibition of viral infection, confirming the view that nuclear import of the viral pre-integration complex is mediated by viral IN.

show abstract

Highly effective inhibition of Akabane virus replication by siRNA genes

Cited by 15 publications

References 29 publications

Small Interfering RNA Inhibition of Andes Virus Replication

Small Interfering RNA Inhibition of Andes Virus Replication

Inhibition of Hazara nairovirus replication by small interfering RNAs and their combination with ribavirin

Inhibition of HIV-1 integrase nuclear import and replication by a peptide bearing integrase putative nuclear localization signal

Contact Info

Product

Resources

About