West Nile virus (WNV) belongs to a group of medically important single-stranded, positive-sense R... more West Nile virus (WNV) belongs to a group of medically important single-stranded, positive-sense RNA viruses causing deadly disease outbreaks around the world. The 3' untranslated region (3'-UTR) of the flavivirus genome, in particular the terminal 3' stem-loop (3'SL) fulfils multiple functions in virus replication and virus-host interactions. Using the Kunjin strain of WNV (WNV(KUN)), we detected a virally encoded small RNA, named KUN-miR-1, derived from 3'SL. Transcription of WNV(KUN) pre-miRNA (3'SL) in mosquito cells either from plasmid or Semliki Forest virus (SFV) RNA replicon resulted in the production of mature KUN-miR-1. Silencing of Dicer-1 but not Dicer-2 led to a reduction in the miRNA levels. Further, when a synthetic inhibitor of KUN-miR-1 was transfected into mosquito cells, replication of viral RNA was significantly reduced. Using cloning and bioinformatics approaches, we identified the cellular GATA4 mRNA as a target for KUN-miR-1. KUN-miR-1 produced in mosquito cells during virus infection or from plasmid DNA, SFV RNA replicon or mature miRNA duplex increased accumulation of GATA4 mRNA. Depletion of GATA4 mRNA by RNA silencing led to a significant reduction in virus RNA replication while a KUN-miR-1 RNA mimic enhanced replication of a mutant WNV(KUN) virus producing reduced amounts of KUN-miR-1, suggesting that GATA4-induction via KUN-miR-1 plays an important role in virus replication.
Parasitoid wasps are valuable biological control agents that suppress their host populations. Fac... more Parasitoid wasps are valuable biological control agents that suppress their host populations. Factors introduced by the female wasp at parasitization play significant roles in facilitating successful development of the parasitoid larva either inside (endoparasitoid) or outside (ectoparasitoid) the host. Wasp venoms consist of a complex cocktail of proteinacious and non-proteinacious components that may offer agrichemicals as well as pharmaceutical components to improve pest management or health related disorders. Undesirably, the constituents of only a small number of wasp venoms are known. In this article, we review the latest research on venom from parasitoid wasps with an emphasis on their biological function, applications and new approaches used in venom studies.
RNA interference (RNAi) is considered as an ancient antiviral-defense in diverse organisms includ... more RNA interference (RNAi) is considered as an ancient antiviral-defense in diverse organisms including insects. Virus infections generate double-strand RNAs (dsRNA) that trigger the RNAi machinery to process dsRNAs into virus-derived siRNAs (vsiRNAs) which target virus genomes, mRNAs or replication intermediates. Viruses, in turn, have evolved suppressors of RNAi (VSR) to counter hosts antiviral RNAi. Following recent discoveries that insects mount the RNAi response against DNA viruses, in this study, we found that Autographa californica MNPV (AcMNPV) infection similarly induces an RNAi response in Spodoptera frugiperda cells by generating a large number of vsiRNAs post-infection. Interestingly, we found that AcMNPV expresses a potent VSR to counter the RNAi. The viral p35 gene, which is well known as an inhibitor of apoptosis, was found responsible for suppression of RNAi in diverse insect and mammalian cells. The VSR activity of p35 was further confirmed by a p35-null AcMNPV that did not suppress the response. In addition, our results showed that the VSR activity is not due to inhibition of dsRNA cleavage by Dicer-2, but acts downstream in the RNAi pathway. Furthermore, we found that the VSR activity is not linked to the anti-apoptotic activity of the protein. Overall, our results provide evidence for the existence of VSR activity from a double-stranded DNA virus, and identify the responsible gene, which is involved in inhibition of RNAi as well as apoptosis. Our findings demonstrate the occurrence of an insect RNAi response against a baculovirus (AcMNPV) that is highly utilized in microbial control, biological and biomedical research, and protein expression. Moreover, our investigations led to the identification of a viral suppressor of RNAi activity and the gene responsible for the activity. Notably, the gene is also a potent inhibitor of apoptosis. The outcomes signify the dual role of a virus-encoded protein to nullify two key antiviral responses, apoptosis and RNAi.
Ascoviruses (AVs) are double-stranded DNA viruses causing a fatal disease in lepidopteran host la... more Ascoviruses (AVs) are double-stranded DNA viruses causing a fatal disease in lepidopteran host larvae. A unique feature of AV infection is cleavage of host cells into membrane bound vesicles containing the virions. A recent study showed that a caspase from Spodoptera frugiperda AV (SfAV) is directly involved in initiation of apoptosis and eventually cell cleavage. Results shown here indicate that Heliothis virescens AV does not induce apoptosis in host cells. HvAV codes for a caspase-like protein but no apoptosis was observed when the gene was expressed in vitro. RNAi studies indicated that the gene is essential for virus replication.
... Host Defence Manipulation by Parasitoid Wasps rubecula (Marshall)/Meris rapae L. and Venturia... more ... Host Defence Manipulation by Parasitoid Wasps rubecula (Marshall)/Meris rapae L. and Venturia canescens Gravenhorst/Epliestia kuehniella Zeller, the ... in calyx nuclei and mode of secretion, but they completely lack nucleic acids (Rotheram 1967; Hedwin 1979; Feddersen etal ...
ABSTRACT The discovery of microRNAs (miRNAs) and their functions has led to a paradigm shift in o... more ABSTRACT The discovery of microRNAs (miRNAs) and their functions has led to a paradigm shift in our understanding of the regulation of gene expression, adding an extra layer of complexity for the mechanisms of gene expression. Both cellular and virus encoded miRNAs play important roles in virus–host interactions that may affect virus replication and the outcome of infection. Recent developments in RNA-seq platforms and bioinformatics tools have accelerated the discovery of miRNAs, their targets, and a myriad of associated research in various species. Here, recent findings and developments in miRNA research pertinent to insect host–virus interactions are reviewed and analyzed.
The role of microRNAs (miRNAs) as small non-coding RNAs in regulation of gene expression has been... more 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.
microRNAs (miRNAs) play significant regulatory roles in gene expression at the post-transcription... more microRNAs (miRNAs) play significant regulatory roles in gene expression at the post-transcriptional level. This includes modulating processes such as development, immunity, cancer, and host-pathogen interactions. It was recently shown that the phylogenetically deeply conserved miRNA, miR-8, plays a role in maintaining the homeostasis of immunity by suppressing the production of anti-microbial peptides. In this study, we show that miR-8 from the insect Plutella xylostella positively regulates the transcript levels of the serine protease inhibitor Serpin 27, which has been shown to regulate activation of the Toll pathway and prophenoloxidase involved in the melanization response in insects. Interestingly, miR-8 is downregulated following parasitization by Diadegma semiclausum leading to significant declines in Serpin 27 transcript levels. This allows upregulation of antimicrobial peptides, such as gloverin, that are controlled by the Toll pathway and activation of proteolytic cascades essential for humoral immune responses to foreign invasion.
MicroRNAs (miRNAs) are small non-coding RNAs that are generated in all eukaryotes and viruses. Th... more MicroRNAs (miRNAs) are small non-coding RNAs that are generated in all eukaryotes and viruses. Their role as master regulators of gene expression in various biological processes has only been fully appreciated over the last decade. Accumulating evidence suggests that alterations in the expression of miRNAs may lead to disorders, including developmental defects, diseases and cancer. Here, I review what is currently known about miRNA functions in insects to provide an insight into their diverse roles in insect biology.
It is now well-established that somatic cells can be reprogrammed to alternative cell fates by ec... more It is now well-established that somatic cells can be reprogrammed to alternative cell fates by ectopic coexpression of defined factors. Reprogramming technology has uncovered a huge plasticity besides gene regulatory networks (GRNs) of differentiated cell states. MicroRNAs (miRNAs), which are an integral part of GRNs, have recently emerged as a powerful reprogramming toolbox. They regulate numerous genes, thereby modulating virtually all cellular processes, including somatic cell reprogramming. Not only can miRNAs provide novel opportunities for interrogating mechanisms of induced pluripotency and direct lineage reprogramming but they also offer hope for the efficient creation of safe cell sources for regenerative medicine. In reviewing landmark roles of miRNAs in cell reprogramming, we offer suggestions for evolution of the reprogramming field.
West Nile virus (WNV) belongs to a group of medically important single-stranded, positive-sense R... more West Nile virus (WNV) belongs to a group of medically important single-stranded, positive-sense RNA viruses causing deadly disease outbreaks around the world. The 3' untranslated region (3'-UTR) of the flavivirus genome, in particular the terminal 3' stem-loop (3'SL) fulfils multiple functions in virus replication and virus-host interactions. Using the Kunjin strain of WNV (WNV(KUN)), we detected a virally encoded small RNA, named KUN-miR-1, derived from 3'SL. Transcription of WNV(KUN) pre-miRNA (3'SL) in mosquito cells either from plasmid or Semliki Forest virus (SFV) RNA replicon resulted in the production of mature KUN-miR-1. Silencing of Dicer-1 but not Dicer-2 led to a reduction in the miRNA levels. Further, when a synthetic inhibitor of KUN-miR-1 was transfected into mosquito cells, replication of viral RNA was significantly reduced. Using cloning and bioinformatics approaches, we identified the cellular GATA4 mRNA as a target for KUN-miR-1. KUN-miR-1 produced in mosquito cells during virus infection or from plasmid DNA, SFV RNA replicon or mature miRNA duplex increased accumulation of GATA4 mRNA. Depletion of GATA4 mRNA by RNA silencing led to a significant reduction in virus RNA replication while a KUN-miR-1 RNA mimic enhanced replication of a mutant WNV(KUN) virus producing reduced amounts of KUN-miR-1, suggesting that GATA4-induction via KUN-miR-1 plays an important role in virus replication.
Parasitoid wasps are valuable biological control agents that suppress their host populations. Fac... more Parasitoid wasps are valuable biological control agents that suppress their host populations. Factors introduced by the female wasp at parasitization play significant roles in facilitating successful development of the parasitoid larva either inside (endoparasitoid) or outside (ectoparasitoid) the host. Wasp venoms consist of a complex cocktail of proteinacious and non-proteinacious components that may offer agrichemicals as well as pharmaceutical components to improve pest management or health related disorders. Undesirably, the constituents of only a small number of wasp venoms are known. In this article, we review the latest research on venom from parasitoid wasps with an emphasis on their biological function, applications and new approaches used in venom studies.
RNA interference (RNAi) is considered as an ancient antiviral-defense in diverse organisms includ... more RNA interference (RNAi) is considered as an ancient antiviral-defense in diverse organisms including insects. Virus infections generate double-strand RNAs (dsRNA) that trigger the RNAi machinery to process dsRNAs into virus-derived siRNAs (vsiRNAs) which target virus genomes, mRNAs or replication intermediates. Viruses, in turn, have evolved suppressors of RNAi (VSR) to counter hosts antiviral RNAi. Following recent discoveries that insects mount the RNAi response against DNA viruses, in this study, we found that Autographa californica MNPV (AcMNPV) infection similarly induces an RNAi response in Spodoptera frugiperda cells by generating a large number of vsiRNAs post-infection. Interestingly, we found that AcMNPV expresses a potent VSR to counter the RNAi. The viral p35 gene, which is well known as an inhibitor of apoptosis, was found responsible for suppression of RNAi in diverse insect and mammalian cells. The VSR activity of p35 was further confirmed by a p35-null AcMNPV that did not suppress the response. In addition, our results showed that the VSR activity is not due to inhibition of dsRNA cleavage by Dicer-2, but acts downstream in the RNAi pathway. Furthermore, we found that the VSR activity is not linked to the anti-apoptotic activity of the protein. Overall, our results provide evidence for the existence of VSR activity from a double-stranded DNA virus, and identify the responsible gene, which is involved in inhibition of RNAi as well as apoptosis. Our findings demonstrate the occurrence of an insect RNAi response against a baculovirus (AcMNPV) that is highly utilized in microbial control, biological and biomedical research, and protein expression. Moreover, our investigations led to the identification of a viral suppressor of RNAi activity and the gene responsible for the activity. Notably, the gene is also a potent inhibitor of apoptosis. The outcomes signify the dual role of a virus-encoded protein to nullify two key antiviral responses, apoptosis and RNAi.
Ascoviruses (AVs) are double-stranded DNA viruses causing a fatal disease in lepidopteran host la... more Ascoviruses (AVs) are double-stranded DNA viruses causing a fatal disease in lepidopteran host larvae. A unique feature of AV infection is cleavage of host cells into membrane bound vesicles containing the virions. A recent study showed that a caspase from Spodoptera frugiperda AV (SfAV) is directly involved in initiation of apoptosis and eventually cell cleavage. Results shown here indicate that Heliothis virescens AV does not induce apoptosis in host cells. HvAV codes for a caspase-like protein but no apoptosis was observed when the gene was expressed in vitro. RNAi studies indicated that the gene is essential for virus replication.
... Host Defence Manipulation by Parasitoid Wasps rubecula (Marshall)/Meris rapae L. and Venturia... more ... Host Defence Manipulation by Parasitoid Wasps rubecula (Marshall)/Meris rapae L. and Venturia canescens Gravenhorst/Epliestia kuehniella Zeller, the ... in calyx nuclei and mode of secretion, but they completely lack nucleic acids (Rotheram 1967; Hedwin 1979; Feddersen etal ...
ABSTRACT The discovery of microRNAs (miRNAs) and their functions has led to a paradigm shift in o... more ABSTRACT The discovery of microRNAs (miRNAs) and their functions has led to a paradigm shift in our understanding of the regulation of gene expression, adding an extra layer of complexity for the mechanisms of gene expression. Both cellular and virus encoded miRNAs play important roles in virus–host interactions that may affect virus replication and the outcome of infection. Recent developments in RNA-seq platforms and bioinformatics tools have accelerated the discovery of miRNAs, their targets, and a myriad of associated research in various species. Here, recent findings and developments in miRNA research pertinent to insect host–virus interactions are reviewed and analyzed.
The role of microRNAs (miRNAs) as small non-coding RNAs in regulation of gene expression has been... more 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.
microRNAs (miRNAs) play significant regulatory roles in gene expression at the post-transcription... more microRNAs (miRNAs) play significant regulatory roles in gene expression at the post-transcriptional level. This includes modulating processes such as development, immunity, cancer, and host-pathogen interactions. It was recently shown that the phylogenetically deeply conserved miRNA, miR-8, plays a role in maintaining the homeostasis of immunity by suppressing the production of anti-microbial peptides. In this study, we show that miR-8 from the insect Plutella xylostella positively regulates the transcript levels of the serine protease inhibitor Serpin 27, which has been shown to regulate activation of the Toll pathway and prophenoloxidase involved in the melanization response in insects. Interestingly, miR-8 is downregulated following parasitization by Diadegma semiclausum leading to significant declines in Serpin 27 transcript levels. This allows upregulation of antimicrobial peptides, such as gloverin, that are controlled by the Toll pathway and activation of proteolytic cascades essential for humoral immune responses to foreign invasion.
MicroRNAs (miRNAs) are small non-coding RNAs that are generated in all eukaryotes and viruses. Th... more MicroRNAs (miRNAs) are small non-coding RNAs that are generated in all eukaryotes and viruses. Their role as master regulators of gene expression in various biological processes has only been fully appreciated over the last decade. Accumulating evidence suggests that alterations in the expression of miRNAs may lead to disorders, including developmental defects, diseases and cancer. Here, I review what is currently known about miRNA functions in insects to provide an insight into their diverse roles in insect biology.
It is now well-established that somatic cells can be reprogrammed to alternative cell fates by ec... more It is now well-established that somatic cells can be reprogrammed to alternative cell fates by ectopic coexpression of defined factors. Reprogramming technology has uncovered a huge plasticity besides gene regulatory networks (GRNs) of differentiated cell states. MicroRNAs (miRNAs), which are an integral part of GRNs, have recently emerged as a powerful reprogramming toolbox. They regulate numerous genes, thereby modulating virtually all cellular processes, including somatic cell reprogramming. Not only can miRNAs provide novel opportunities for interrogating mechanisms of induced pluripotency and direct lineage reprogramming but they also offer hope for the efficient creation of safe cell sources for regenerative medicine. In reviewing landmark roles of miRNAs in cell reprogramming, we offer suggestions for evolution of the reprogramming field.
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