Are viral small RNA regulating Dengue virus replication beyond serotype 2?

Finol, Esteban

doi:10.1073/pnas.1409972111

Cited by 9 publications

(7 citation statements)

References 5 publications

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“…The significance of viral miRNA production from DENV genomic RNA is heavily debated [ 24 – 26 , 54 ]. To investigate whether viral miRNA-like molecules are produced in DENV2 infected Aag2 cells, we filtered 22–24 nt small RNA reads that map to the DENV2 genome with a maximum of one mismatch.…”

Section: Resultsmentioning

confidence: 99%

“…However, functional introduction of artificial miRNAs into the genomes of Sindbis virus (SINV) and tick-borne encephalitis virus provides evidence that miRNA production from cytoplasmic RNA viruses may in principle be possible [ 22 , 23 ]. Yet, the presence and biological relevance of miRNAs encoded in the genomes of flaviviruses such as DENV is still an issue of debate [ 24 – 26 ].…”

Section: Introductionmentioning

confidence: 99%

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Small RNA Profiling in Dengue Virus 2-Infected Aedes Mosquito Cells Reveals Viral piRNAs and Novel Host miRNAs

et al. 2016

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In Aedes mosquitoes, infections with arthropod-borne viruses (arboviruses) trigger or modulate the expression of various classes of viral and host-derived small RNAs, including small interfering RNAs (siRNAs), PIWI interacting RNAs (piRNAs), and microRNAs (miRNAs). Viral siRNAs are at the core of the antiviral RNA interference machinery, one of the key pathways that limit virus replication in invertebrates. Besides siRNAs, Aedes mosquitoes and cells derived from these insects produce arbovirus-derived piRNAs, the best studied examples being viruses from the Togaviridae or Bunyaviridae families. Host miRNAs modulate the expression of a large number of genes and their levels may change in response to viral infections. In addition, some viruses, mostly with a DNA genome, express their own miRNAs to regulate host and viral gene expression. Here, we perform a comprehensive analysis of both viral and host-derived small RNAs in Aedes aegypti Aag2 cells infected with dengue virus 2 (DENV), a member of the Flaviviridae family. Aag2 cells are competent in producing all three types of small RNAs and provide a powerful tool to explore the crosstalk between arboviral infection and the distinct RNA silencing pathways. Interestingly, besides the well-characterized DENV-derived siRNAs, a specific population of viral piRNAs was identified in infected Aag2 cells. Knockdown of Piwi5, Ago3 and, to a lesser extent, Piwi6 results in reduction of vpiRNA levels, providing the first genetic evidence that Aedes PIWI proteins produce DENV-derived small RNAs. In contrast, we do not find convincing evidence for the production of virus-derived miRNAs. Neither do we find that host miRNA expression is strongly changed upon DENV2 infection. Finally, our deep-sequencing analyses detect 30 novel Aedes miRNAs, complementing the repertoire of regulatory small RNAs in this important vector species.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Small RNA Profiling in Dengue Virus 2-Infected Aedes Mosquito Cells Reveals Viral piRNAs and Novel Host miRNAs

et al. 2016

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“…Precursors of many of these viral-encoded miRNAs are transcribed in the nucleus by host cell RNA polymerases II or III and exported to the cytoplasm by mechanisms that do not involve Drosha excision of the pre-miRNA from the viral mRNA or genome [ 88 ]. There have been two reports of miRNAs encoded in the 3'-UTRs of flavivirus genomes [ 109 , 110 ]; however, comments from other investigators [ 111 , 112 ] have raised questions about the general applicability of these findings.…”

Section: Does the Mirna Pathway Have A Role In Arbovirus-vector Inmentioning

confidence: 99%

The Role of RNA Interference (RNAi) in Arbovirus-Vector Interactions

Blair

Olson

2015

Viruses

137

132

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RNA interference (RNAi) was shown over 18 years ago to be a mechanism by which arbovirus replication and transmission could be controlled in arthropod vectors. During the intervening period, research on RNAi has defined many of the components and mechanisms of this antiviral pathway in arthropods, yet a number of unexplored questions remain. RNAi refers to RNA-mediated regulation of gene expression. Originally, the term described silencing of endogenous genes by introduction of exogenous double-stranded (ds)RNA with the same sequence as the gene to be silenced. Further research has shown that RNAi comprises three gene regulation pathways that are mediated by small RNAs: the small interfering (si)RNA, micro (mi)RNA, and Piwi-interacting (pi)RNA pathways. The exogenous (exo-)siRNA pathway is now recognized as a major antiviral innate immune response of arthropods. More recent studies suggest that the piRNA and miRNA pathways might also have important roles in arbovirus-vector interactions. This review will focus on current knowledge of the role of the exo-siRNA pathway as an arthropod vector antiviral response and on emerging research into vector piRNA and miRNA pathway modulation of arbovirus-vector interactions. Although it is assumed that arboviruses must evade the vector’s antiviral RNAi response in order to maintain their natural transmission cycles, the strategies by which this is accomplished are not well defined. RNAi is also an important tool for arthropod gene knock-down in functional genomics studies and in development of arbovirus-resistant mosquito populations. Possible arbovirus strategies for evasion of RNAi and applications of RNAi in functional genomics analysis and arbovirus transmission control will also be reviewed.

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“…Considering that one long transcript is produced during DENV replication, which consists of structural as well as non-structural proteins, targeting NS1 by vsRNA-5 basically means that the virus genome is targeted. A follow up bioinformatics analysis revealed that vsRNA-5 and its NS1 target sequences might be mainly conserved in DENV serotype 2 and not in the other serotypes [ 70 ].…”

Section: Role Of Mirnas In Vector-arbovirus Interactionsmentioning

confidence: 99%

Role of microRNAs in Arbovirus/Vector Interactions

Asgari

2014

Viruses

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The role of microRNAs (miRNAs) as small non-coding RNAs in regulation of gene expression has been recognized. They appear to be involved in regulation of a wide range of cellular pathways that affect several biological processes such as development, the immune system, survival, metabolism and host-pathogen interactions. Arthropod-borne viruses impose great economic and health risks around the world. Recent advances in miRNA biology have shed some light on the role of these small RNAs in vector-virus interactions. In this review, I will reflect on our current knowledge on the role of miRNAs in arbovirus-vector interactions and the potential avenues for their utilization in limiting virus replication and/or transmission.

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Are viral small RNA regulating Dengue virus replication beyond serotype 2?

Cited by 9 publications

References 5 publications

Small RNA Profiling in Dengue Virus 2-Infected Aedes Mosquito Cells Reveals Viral piRNAs and Novel Host miRNAs

Small RNA Profiling in Dengue Virus 2-Infected Aedes Mosquito Cells Reveals Viral piRNAs and Novel Host miRNAs

The Role of RNA Interference (RNAi) in Arbovirus-Vector Interactions

Role of microRNAs in Arbovirus/Vector Interactions

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