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Gaya K. Amarasinghe - One of the best experts on this subject based on the ideXlab platform.
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Taxonomy of the order Mononegavirales: update 2019.
Archives of virology, 2019Co-Authors: Gaya K. Amarasinghe, Christopher F. Basler, Sina Bavari, Kim R. Blasdell, Thomas Briese, Alexander Bukreyev, María A. Ayllón, Paul A. Brown, Yīmíng Bào, Anne Balkema-buschmannAbstract:In February 2019, following the annual taxon ratification vote, the order Mononegavirales was amended by the addition of four new subfamilies and 12 new genera and the creation of 28 novel species. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV).
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Taxonomy of the order Mononegavirales: second update 2018
Archives of virology, 2019Co-Authors: Piet Maes, Gaya K. Amarasinghe, Christopher F. Basler, Sina Bavari, Kim R. Blasdell, Thomas Briese, Alexander Bukreyev, María A. Ayllón, Paul A. Brown, Anne Balkema-buschmannAbstract:In October 2018, the order Mononegavirales was amended by the establishment of three new families and three new genera, abolishment of two genera, and creation of 28 novel species. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV).
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Taxonomy of the order Mononegavirales: update 2018
Archives of Virology, 2018Co-Authors: Gaya K. Amarasinghe, Christopher F. Basler, Sina Bavari, Kim R. Blasdell, Thomas Briese, Alexander Bukreyev, Nidia G. Aréchiga Ceballos, Ashley C. Banyard, Andrew J. Bennett, Yingyún CaiAbstract:In 2018, the order Mononegavirales was expanded by inclusion of 1 new genus and 12 novel species. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV) and summarizes additional taxonomic proposals that may affect the order in the near future.
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Taxonomy of the order Mononegavirales: update 2017
Archives of Virology, 2017Co-Authors: Gaya K. Amarasinghe, Yiming Bào, Christopher F. Basler, Sina Bavari, Martin Beer, Nicolás Bejerman, Kim R. Blasdell, Alisa Bochnowski, Thomas Briese, Alexander BukreyevAbstract:In 2017, the order Mononegavirales was expanded by the inclusion of a total of 69 novel species. Five new rhabdovirus genera and one new nyamivirus genus were established to harbor 41 of these species, whereas the remaining new species were assigned to already established genera. Furthermore, non-Latinized binomial species names replaced all paramyxovirus and pneumovirus species names, thereby accomplishing application of binomial species names throughout the entire order. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV).
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Possibility and Challenges of Conversion of Current Virus Species Names to Linnaean Binomials
Systematic biology, 2017Co-Authors: Thomas S. Postler, Gaya K. Amarasinghe, Christopher F. Basler, Sina Bavari, Kim R. Blasdell, Thomas Briese, Anna N. Clawson, Mária Benko, Michael J. Buchmeier, Alexander BukreyevAbstract:Botanical, mycological, zoological, and prokaryotic species names follow the Linnaean format, consisting of an italicized Latinized binomen with a capitalized genus name and a lower case species epithet (e.g., Homo sapiens). Virus species names, however, do not follow a uniform format, and, even when binomial, are not Linnaean in style. In this thought exercise, we attempted toconvert all currently official names ofspecies included in the virusfamily Arenaviridae and the virus order Mononegavirales to Linnaean binomials, and to identify and address associated challenges and concerns. Surprisingly, this endeavor was not as complicated or time-consuming as even the authors of this article expected when conceiving the experiment.
Valery Z. Grdzelishvili - One of the best experts on this subject based on the ideXlab platform.
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Sequence-Function Analysis of the Sendai virus L protein domain VI
Virology, 2010Co-Authors: Andrea M. Murphy, Megan Moerdyk-schauwecker, Arcady Mushegian, Valery Z. GrdzelishviliAbstract:Abstract The large (about 2200 amino acids) L polymerase protein of nonsegmented negative-strand RNA viruses (order Mononegavirales ) has six conserved sequence regions (“domains”) postulated to constitute the specific enzymatic activities involved in viral mRNA synthesis, 5′-end capping, cap methylation, 3′ polyadenylation, and genomic RNA replication. Previous studies with vesicular stomatitis virus identified amino acid residues within the L protein domain VI required for mRNA cap methylation. In our recent study we analyzed four amino acid residues within domain VI of the Sendai virus L protein and our data indicated that there could be differences in L protein sequence requirements for cap methylation in two different families of Mononegavirales — rhabdoviruses and paramyxoviruses. In this study, we conducted a more comprehensive mutational analysis by targeting the entire SeV L protein domain VI, creating twenty-four L mutants, and testing these mutations for their effects on viral mRNA synthesis, cap methylation, viral genome replication and virus growth kinetics. Our analysis identified several residues required for successful cap methylation and virus replication and clearly showed the importance of the K-D-K-E tetrad and glycine-rich motif in the SeV cap methylation. This study is the first extensive sequence analysis of the L protein domain VI in the family Paramyxoviridae , and it confirms structural and functional similarity of this domain across different families of the order Mononegavirales .
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Analysis of virion associated host proteins in vesicular stomatitis virus using a proteomics approach.
Virology journal, 2009Co-Authors: Megan Moerdyk-schauwecker, Sun-il Hwang, Valery Z. GrdzelishviliAbstract:Background Vesicular stomatitis virus (VSV) is the prototypic rhabdovirus and the best studied member of the order Mononegavirales. There is now compelling evidence that enveloped virions released from infected cells carry numerous host (cellular) proteins some of which may play an important role in viral replication. Although several cellular proteins have been previously shown to be incorporated into VSV virions, no systematic study has been done to reveal the host protein composition for virions of VSV or any other member of Mononegavirales.
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Analysis of virion associated host proteins in vesicular stomatitis virus using a proteomics approach
Virology Journal, 2009Co-Authors: Megan Moerdyk-schauwecker, Sun-il Hwang, Valery Z. GrdzelishviliAbstract:Background Vesicular stomatitis virus (VSV) is the prototypic rhabdovirus and the best studied member of the order Mononegavirales . There is now compelling evidence that enveloped virions released from infected cells carry numerous host (cellular) proteins some of which may play an important role in viral replication. Although several cellular proteins have been previously shown to be incorporated into VSV virions, no systematic study has been done to reveal the host protein composition for virions of VSV or any other member of Mononegavirales . Results Here we used a proteomics approach to identify cellular proteins within purified VSV virions, thereby creating a "snapshot" of one stage of virus/host interaction that can guide future experiments aimed at understanding molecular mechanisms of virus-cell interactions. Highly purified preparations of VSV virions from three different cell lines of human, mouse and hamster origin were analyzed for the presence of cellular proteins using mass spectrometry. We have successfully confirmed the presence of several previously-identified cellular proteins within VSV virions and identified a number of additional proteins likely to also be present within the virions. In total, sixty-four cellular proteins were identified, of which nine were found in multiple preparations. A combination of immunoblotting and proteinase K protection assay was used to verify the presence of several of these proteins (integrin β1, heat shock protein 90 kDa, heat shock cognate 71 kDa protein, annexin 2, elongation factor 1a) within the virions. Conclusion This is, to our knowledge, the first systematic study of the host protein composition for virions of VSV or any other member of the order Mononegavirales . Future experiments are needed to determine which of the identified proteins have an interaction with VSV and whether these interactions are beneficial, neutral or antiviral with respect to VSV replication. Identification of host proteins-virus interactions beneficial for virus would be particularly exciting as they can provide new ways to combat viral infections via control of host components.
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Identification of Sendai Virus L Protein Amino Acid Residues Affecting Viral mRNA Cap Methylation
Journal of virology, 2008Co-Authors: Andrea M. Murphy, Valery Z. GrdzelishviliAbstract:Viruses of the order Mononegavirales all encode a large (L) polymerase protein responsible for the replication and transcription of the viral genome as well as all posttranscriptional modifications of viral mRNAs. The L protein is conserved among all members of the Mononegavirales and has six conserved regions (“domains”). Using vesicular stomatitis virus (VSV) (family Rhabdoviridae) experimental system, we and others recently identified several conserved amino acid residues within L protein domain VI which are required for viral mRNA cap methylation. To verify that these critical amino acid residues have a similar function in other members of the Mononegavirales, we examined the Sendai virus (SeV) (family Paramyxoviridae) L protein by targeting homologous amino acid residues important for cap methylation in VSV which are highly conserved among all members of the Mononegavirales and are believed to constitute the L protein catalytic and S-adenosylmethionine-binding sites. In addition, an SeV L protein mutant with a deletion of the entire domain VI was generated. First, L mutants were tested for their abilities to synthesize viral mRNAs. While the domain VI deletion completely inactivated L, most of the amino acid substitutions had minor effects on mRNA synthesis. Using a reverse genetics approach, these mutations were introduced into the SeV genome, and recombinant infectious SeV mutants with single alanine substitutions at L positions 1782, 1804, 1805, and 1806 or a double substitution at positions 1804 and 1806 were generated. The mutant SeV virions were purified, detergent activated, and analyzed for their abilities to synthesize viral mRNAs methylated at their cap structures. In addition, further studies were done to examine these SeV mutants for a possible host range phenotype, which was previously shown for VSV cap methylation-defective mutants. In agreement with a predicted role of the SeV L protein invariant lysine 1782 as a catalytic residue, the recombinant virus with a single K1782A substitution was completely defective in cap methylation and showed a host range phenotype. In addition, the E1805A mutation within the putative S-adenosylmethionine-binding site of L resulted in a 60% reduction in cap methylation. In contrast to the homologous VSV mutants, other recombinant SeV mutants with amino acid substitutions at this site were neither defective in cap methylation nor host range restricted. The results of this initial study using an SeV experimental system demonstrate similarities as well as differences between the L protein cap methylation domains in different members of the Mononegavirales.
Alexander Bukreyev - One of the best experts on this subject based on the ideXlab platform.
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Taxonomy of the order Mononegavirales: update 2019.
Archives of virology, 2019Co-Authors: Gaya K. Amarasinghe, Christopher F. Basler, Sina Bavari, Kim R. Blasdell, Thomas Briese, Alexander Bukreyev, María A. Ayllón, Paul A. Brown, Yīmíng Bào, Anne Balkema-buschmannAbstract:In February 2019, following the annual taxon ratification vote, the order Mononegavirales was amended by the addition of four new subfamilies and 12 new genera and the creation of 28 novel species. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV).
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Taxonomy of the order Mononegavirales: second update 2018
Archives of virology, 2019Co-Authors: Piet Maes, Gaya K. Amarasinghe, Christopher F. Basler, Sina Bavari, Kim R. Blasdell, Thomas Briese, Alexander Bukreyev, María A. Ayllón, Paul A. Brown, Anne Balkema-buschmannAbstract:In October 2018, the order Mononegavirales was amended by the establishment of three new families and three new genera, abolishment of two genera, and creation of 28 novel species. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV).
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Taxonomy of the order Mononegavirales: update 2018
Archives of Virology, 2018Co-Authors: Gaya K. Amarasinghe, Christopher F. Basler, Sina Bavari, Kim R. Blasdell, Thomas Briese, Alexander Bukreyev, Nidia G. Aréchiga Ceballos, Ashley C. Banyard, Andrew J. Bennett, Yingyún CaiAbstract:In 2018, the order Mononegavirales was expanded by inclusion of 1 new genus and 12 novel species. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV) and summarizes additional taxonomic proposals that may affect the order in the near future.
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Taxonomy of the order Mononegavirales: update 2017
Archives of Virology, 2017Co-Authors: Gaya K. Amarasinghe, Yiming Bào, Christopher F. Basler, Sina Bavari, Martin Beer, Nicolás Bejerman, Kim R. Blasdell, Alisa Bochnowski, Thomas Briese, Alexander BukreyevAbstract:In 2017, the order Mononegavirales was expanded by the inclusion of a total of 69 novel species. Five new rhabdovirus genera and one new nyamivirus genus were established to harbor 41 of these species, whereas the remaining new species were assigned to already established genera. Furthermore, non-Latinized binomial species names replaced all paramyxovirus and pneumovirus species names, thereby accomplishing application of binomial species names throughout the entire order. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV).
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Possibility and Challenges of Conversion of Current Virus Species Names to Linnaean Binomials
Systematic biology, 2017Co-Authors: Thomas S. Postler, Gaya K. Amarasinghe, Christopher F. Basler, Sina Bavari, Kim R. Blasdell, Thomas Briese, Anna N. Clawson, Mária Benko, Michael J. Buchmeier, Alexander BukreyevAbstract:Botanical, mycological, zoological, and prokaryotic species names follow the Linnaean format, consisting of an italicized Latinized binomen with a capitalized genus name and a lower case species epithet (e.g., Homo sapiens). Virus species names, however, do not follow a uniform format, and, even when binomial, are not Linnaean in style. In this thought exercise, we attempted toconvert all currently official names ofspecies included in the virusfamily Arenaviridae and the virus order Mononegavirales to Linnaean binomials, and to identify and address associated challenges and concerns. Surprisingly, this endeavor was not as complicated or time-consuming as even the authors of this article expected when conceiving the experiment.
Thomas Briese - One of the best experts on this subject based on the ideXlab platform.
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Taxonomy of the order Mononegavirales: update 2019.
Archives of virology, 2019Co-Authors: Gaya K. Amarasinghe, Christopher F. Basler, Sina Bavari, Kim R. Blasdell, Thomas Briese, Alexander Bukreyev, María A. Ayllón, Paul A. Brown, Yīmíng Bào, Anne Balkema-buschmannAbstract:In February 2019, following the annual taxon ratification vote, the order Mononegavirales was amended by the addition of four new subfamilies and 12 new genera and the creation of 28 novel species. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV).
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Taxonomy of the order Mononegavirales: second update 2018
Archives of virology, 2019Co-Authors: Piet Maes, Gaya K. Amarasinghe, Christopher F. Basler, Sina Bavari, Kim R. Blasdell, Thomas Briese, Alexander Bukreyev, María A. Ayllón, Paul A. Brown, Anne Balkema-buschmannAbstract:In October 2018, the order Mononegavirales was amended by the establishment of three new families and three new genera, abolishment of two genera, and creation of 28 novel species. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV).
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Taxonomy of the order Mononegavirales: update 2018
Archives of Virology, 2018Co-Authors: Gaya K. Amarasinghe, Christopher F. Basler, Sina Bavari, Kim R. Blasdell, Thomas Briese, Alexander Bukreyev, Nidia G. Aréchiga Ceballos, Ashley C. Banyard, Andrew J. Bennett, Yingyún CaiAbstract:In 2018, the order Mononegavirales was expanded by inclusion of 1 new genus and 12 novel species. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV) and summarizes additional taxonomic proposals that may affect the order in the near future.
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Taxonomy of the order Mononegavirales: update 2017
Archives of Virology, 2017Co-Authors: Gaya K. Amarasinghe, Yiming Bào, Christopher F. Basler, Sina Bavari, Martin Beer, Nicolás Bejerman, Kim R. Blasdell, Alisa Bochnowski, Thomas Briese, Alexander BukreyevAbstract:In 2017, the order Mononegavirales was expanded by the inclusion of a total of 69 novel species. Five new rhabdovirus genera and one new nyamivirus genus were established to harbor 41 of these species, whereas the remaining new species were assigned to already established genera. Furthermore, non-Latinized binomial species names replaced all paramyxovirus and pneumovirus species names, thereby accomplishing application of binomial species names throughout the entire order. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV).
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Possibility and Challenges of Conversion of Current Virus Species Names to Linnaean Binomials
Systematic biology, 2017Co-Authors: Thomas S. Postler, Gaya K. Amarasinghe, Christopher F. Basler, Sina Bavari, Kim R. Blasdell, Thomas Briese, Anna N. Clawson, Mária Benko, Michael J. Buchmeier, Alexander BukreyevAbstract:Botanical, mycological, zoological, and prokaryotic species names follow the Linnaean format, consisting of an italicized Latinized binomen with a capitalized genus name and a lower case species epithet (e.g., Homo sapiens). Virus species names, however, do not follow a uniform format, and, even when binomial, are not Linnaean in style. In this thought exercise, we attempted toconvert all currently official names ofspecies included in the virusfamily Arenaviridae and the virus order Mononegavirales to Linnaean binomials, and to identify and address associated challenges and concerns. Surprisingly, this endeavor was not as complicated or time-consuming as even the authors of this article expected when conceiving the experiment.
Denis Gerlier - One of the best experts on this subject based on the ideXlab platform.
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hsp90 chaperoning in addition to phosphoprotein required for folding but not for supporting enzymatic activities of measles and nipah virus l polymerases
Journal of Virology, 2016Co-Authors: Louismarie Bloyet, Jeremy Charles Welsch, Francois Enchery, Cyrille Mathieu, Sylvain De Breyne, Branka Horvat, Boyan Grigorov, Denis GerlierAbstract:ABSTRACT Nonsegmented negative-stranded RNA viruses, or members of the order Mononegavirales, share a conserved gene order and the use of elaborate transcription and replication machinery made up of at least four molecular partners. These partners have coevolved with the acquisition of the permanent encapsidation of the entire genome by the nucleoprotein (N) and the use of this N-RNA complex as a template for the viral polymerase composed of the phosphoprotein (P) and the large enzymatic protein (L). Not only is P required for polymerase function, but it also stabilizes the L protein through an unknown underlying molecular mechanism. By using NVP-AUY922 and/or 17-dimethylaminoethylamino-17-demethoxygeldanamycin as specific inhibitors of cellular heat shock protein 90 (HSP90), we found that efficient chaperoning of L by HSP90 requires P in the measles, Nipah, and vesicular stomatitis viruses. While the production of P remains unchanged in the presence of HSP90 inhibitors, the production of soluble and functional L requires both P and HSP90 activity. Measles virus P can bind the N terminus of L in the absence of HSP90 activity. Both HSP90 and P are required for the folding of L, as evidenced by a luciferase reporter insert fused within measles virus L. HSP90 acts as a true chaperon; its activity is transient and dispensable for the activity of measles and Nipah virus polymerases of virion origin. That the cellular chaperoning of a viral polymerase into a soluble functional enzyme requires the assistance of another viral protein constitutes a new paradigm that seems to be conserved within the Mononegavirales order. IMPORTANCE Viruses are obligate intracellular parasites that require a cellular environment for their replication. Some viruses particularly depend on the cellular chaperoning apparatus. We report here that for measles virus, successful chaperoning of the viral L polymerase mediated by heat shock protein 90 (HSP90) requires the presence of the viral phosphoprotein (P). Indeed, while P protein binds to the N terminus of L independently of HSP90 activity, both HSP90 and P are required to produce stable, soluble, folded, and functional L proteins. Once formed, the mature P+L complex no longer requires HSP90 to exert its polymerase functions. Such a new paradigm for the maturation of a viral polymerase appears to be conserved in several members of the Mononegavirales order, including the Nipah and vesicular stomatitis viruses.
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transcription et replication des Mononegavirales une machine moleculaire originale
Virologie, 2012Co-Authors: David Blocquel, Jean Francois Eleouet, Sonia Longhi, Jeanmarie Bourhis, Denis Gerlier, Johnny Habchi, Marc Jamin, Filip YabukarskiAbstract:Viruses with a non-segmented negative-sense RNA genome, or Mononegavirales, are important pathogens for plants, animals and humans with major socio-economic and health impacts. Among them are well-known human pathogens such as measles, mumps and respiratory syncytial virus. Moreover, animal reservoirs appear much larger than previously thought, hence broadening the risk of emergence of life-threatening zoonotic viruses such as Rabies, Ebola, Marburg, Nipah or Hendra related viruses. These viruses have peculiar transcription and replication machinery that make them unique in the living world. Indeed, their genomic RNA, when naked, is non-infectious because it can be neither transcribed nor translated, and the L RNA-dependent RNA-polymerase is at best able to initiate the synthesis of an RNA copy of a few of tens of nucleotides in length. To serve as a template, the genomic RNA must be encapsidated in a helicoidal homopolymer made of a regular and continuous array of docked N protomers in which the ribose-phosphate backbone is fully embedded. This complex, or nucleocapsid, is recognized by the L polymerase thanks to its cofactor, the P protein, to sequentially transcribe the five genes into five processed mRNAs for the simplest viruses. Subsequently, a switch occurs and the polymerase replicates a full copy of antigenomic RNA that is concurrently encapsidated. This new template is then used for the production of new infectious genomic nucleocapsids. This review summarizes current structural, dynamic and functional data of this peculiar molecular machinery and provides a unified model of how it can function. It illuminates the overall common strategies and the subtle variations in the different viruses, along with the key role of the dual ordered/disordered structure of the protein components in the dynamics of the viral polymerase machinery.
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Interplay between Innate Immunity and Negative-Strand RNA Viruses: towards a Rational Model
Microbiology and Molecular Biology Reviews, 2011Co-Authors: Denis Gerlier, Douglas S. LylesAbstract:SUMMARY The discovery of a new class of cytosolic receptors recognizing viral RNA, called the RIG-like receptors (RLRs), has revolutionized our understanding of the interplay between viruses and host cells. A tremendous amount of work has been accumulating to decipher the RNA moieties required for an RLR agonist, the signal transduction pathway leading to activation of the innate immunity orchestrated by type I interferon (IFN), the cellular and viral regulators of this pathway, and the viral inhibitors of the innate immune response. Previous reviews have focused on the RLR signaling pathway and on the negative regulation of the interferon response by viral proteins. The focus of this review is to put this knowledge in the context of the virus replication cycle within a cell. Likewise, there has been an expansion of knowledge about the role of innate immunity in the pathophysiology of viral infection. As a consequence, some discrepancies have arisen between the current models of cell-intrinsic innate immunity and current knowledge of virus biology. This holds particularly true for the nonsegmented negative-strand viruses (Mononegavirales), which paradoxically have been largely used to build presently available models. The aim of this review is to bridge the gap between the virology and innate immunity to favor the rational building of a relevant model(s) describing the interplay between Mononegavirales and the innate immune system.
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cytosolic 5 triphosphate ended viral leader transcript of measles virus as activator of the rig i mediated interferon response
PLOS ONE, 2007Co-Authors: Sebastien Plumet, Sonia Longhi, Florence Herschke, Jeanmarie Bourhis, Helene Valentin, Denis GerlierAbstract:Background Double stranded RNA (dsRNA) is widely accepted as an RNA motif recognized as a danger signal by the cellular sentries. However, the biology of non-segmented negative strand RNA viruses, or Mononegavirales, is hardly compatible with the production of such dsRNA. Methodology and Principal Findings During measles virus infection, the IFN-β gene transcription was found to be paralleled by the virus transcription, but not by the virus replication. Since the expression of every individual viral mRNA failed to activate the IFN-β gene, we postulated the involvement of the leader RNA, which is a small not capped and not polyadenylated RNA firstly transcribed by Mononegavirales. The measles virus leader RNA, synthesized both in vitro and in vivo, was efficient in inducing the IFN-β expression, provided that it was delivered into the cytosol as a 5′-trisphosphate ended RNA. The use of a human cell line expressing a debilitated RIG-I molecule, together with overexpression studies of wild type RIG-I, showed that the IFN-β induction by virus infection or by leader RNA required RIG-I to be functional. RIG-I binds to leader RNA independently from being 5-trisphosphate ended; while a point mutant, Q299A, predicted to establish contacts with the RNA, fails to bind to leader RNA. Since the 5′-triphosphate is required for optimal RIG-I activation but not for leader RNA binding, our data support that RIG-I is activated upon recognition of the 5′-triphosphate RNA end. Conclusions/Significance RIG-I is proposed to recognize Mononegavirales transcription, which occurs in the cytosol, while scanning cytosolic RNAs, and to trigger an IFN response when encountering a free 5′-triphosphate RNA resulting from a mislocated transcription activity, which is therefore considered as the hallmark of a foreign invader.
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Cytosolic 5′-Triphosphate Ended Viral Leader Transcript of Measles Virus as Activator of the RIG I-Mediated Interferon Response
PloS one, 2007Co-Authors: Sebastien Plumet, Sonia Longhi, Florence Herschke, Jeanmarie Bourhis, Helene Valentin, Denis GerlierAbstract:Background Double stranded RNA (dsRNA) is widely accepted as an RNA motif recognized as a danger signal by the cellular sentries. However, the biology of non-segmented negative strand RNA viruses, or Mononegavirales, is hardly compatible with the production of such dsRNA. Methodology and Principal Findings During measles virus infection, the IFN-β gene transcription was found to be paralleled by the virus transcription, but not by the virus replication. Since the expression of every individual viral mRNA failed to activate the IFN-β gene, we postulated the involvement of the leader RNA, which is a small not capped and not polyadenylated RNA firstly transcribed by Mononegavirales. The measles virus leader RNA, synthesized both in vitro and in vivo, was efficient in inducing the IFN-β expression, provided that it was delivered into the cytosol as a 5′-trisphosphate ended RNA. The use of a human cell line expressing a debilitated RIG-I molecule, together with overexpression studies of wild type RIG-I, showed that the IFN-β induction by virus infection or by leader RNA required RIG-I to be functional. RIG-I binds to leader RNA independently from being 5-trisphosphate ended; while a point mutant, Q299A, predicted to establish contacts with the RNA, fails to bind to leader RNA. Since the 5′-triphosphate is required for optimal RIG-I activation but not for leader RNA binding, our data support that RIG-I is activated upon recognition of the 5′-triphosphate RNA end. Conclusions/Significance RIG-I is proposed to recognize Mononegavirales transcription, which occurs in the cytosol, while scanning cytosolic RNAs, and to trigger an IFN response when encountering a free 5′-triphosphate RNA resulting from a mislocated transcription activity, which is therefore considered as the hallmark of a foreign invader.