scholarly journals Specificity of resistance to dengue virus isolates is associated with genotypes of the mosquito antiviral gene Dicer-2

2013 ◽  
Vol 280 (1751) ◽  
pp. 20122437 ◽  
Author(s):  
Louis Lambrechts ◽  
Elsa Quillery ◽  
Valérie Noël ◽  
Jason H. Richardson ◽  
Richard G. Jarman ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Rna Virus ◽  
Rnai Pathway ◽  
Allelic Polymorphism ◽  
Immune Gene ◽  
Causal Polymorphism ◽  
Host Pathogen ◽  
Natural Polymorphism ◽  
Genotype Interaction ◽  
Genetic Specificity

In contrast to the prevailing view that invertebrate immunity relies on broad-spectrum recognition and effector mechanisms, intrinsic genetic compatibility between invertebrate hosts and their pathogens is often highly specific in nature. Solving this puzzle requires a better understanding of the molecular basis underlying observed patterns of invertebrate host–pathogen genetic specificity, broadly referred to as genotype-by-genotype interactions. Here, we identify an invertebrate immune gene in which natural polymorphism is associated with isolate-specific resistance to an RNA virus. Dicer-2 ( dcr2 ) encodes a key protein upstream of the RNA interference (RNAi) pathway, a major antiviral component of innate immunity in invertebrates. We surveyed allelic polymorphism at the dcr2 locus in a wild-type outbred population and in three derived isofemale families of the mosquito Aedes aegypti that were experimentally exposed to several, genetically distinct isolates of dengue virus. We found that dcr2 genotype was associated with resistance to dengue virus in a virus isolate-specific manner. By contrast, no such association was found for genotypes at two control loci flanking dcr2 , making it likely that dcr2 contains the yet-unidentified causal polymorphism(s). This result supports the idea that host–pathogen compatibility in this system depends, in part, on a genotype-by-genotype interaction between dcr2 and the viral genome, and points to the RNAi pathway as a potentially important determinant of intrinsic insect-virus genetic specificity.

scholarly journals A deletion polymorphism in the Caenorhabditis elegans RIG-I homolog disables viral RNA dicing and antiviral immunity

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Alyson Ashe ◽  
Tony Bélicard ◽  
Jérémie Le Pen ◽  
Peter Sarkies ◽  
Lise Frézal ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Genome Wide Association Study ◽  
Rna Virus ◽  
Rnai Pathway ◽  
Animal Cells ◽  
C Elegans ◽  
Base Pair Deletion ◽  
A Genome ◽  
Positive Strand Rna ◽  
Viral Recognition

RNA interference defends against viral infection in plant and animal cells. The nematode Caenorhabditis elegans and its natural pathogen, the positive-strand RNA virus Orsay, have recently emerged as a new animal model of host-virus interaction. Using a genome-wide association study in C. elegans wild populations and quantitative trait locus mapping, we identify a 159 base-pair deletion in the conserved drh-1 gene (encoding a RIG-I-like helicase) as a major determinant of viral sensitivity. We show that DRH-1 is required for the initiation of an antiviral RNAi pathway and the generation of virus-derived siRNAs (viRNAs). In mammals, RIG-I-domain containing proteins trigger an interferon-based innate immunity pathway in response to RNA virus infection. Our work in C. elegans demonstrates that the RIG-I domain has an ancient role in viral recognition. We propose that RIG-I acts as modular viral recognition factor that couples viral recognition to different effector pathways including RNAi and interferon responses.

scholarly journals Dengue virus: A review

2022 ◽  
Vol 8 (4) ◽  
pp. 243-247
Author(s):  
Narinder Singh ◽  
Ajeet Pal Singh ◽  
Amar Pal Singh
Keyword(s):  
Public Health ◽  
Dengue Virus ◽  
Dengue Fever ◽  
Rna Virus ◽  
Hemorrhagic Fever ◽  
Health Concern ◽  
Virus Infections ◽  
Public Health Concern ◽  
Viral Illness ◽  
Life Threatening

Dengue fever is a mosquito-borne viral illness that is quickly spreading over the globe, with significant death and morbidity rates. Dengue fever is an acute viral infection transmitted by Aedes mosquitos and caused by an RNA virus from the Flaviviridae family. The symptoms might vary from asymptomatic fever to life-threatening complications including hemorrhagic fever and shock. Although dengue virus infections are normally self-limiting, the disease has become a public health concern in tropical and subtropical countries. Dengue fever is a major public health concern owing to its rapid worldwide spread, and its burdens are now unmet due to a lack of accurate therapy and a simple diagnostic approach for the early stages of illness.

scholarly journals PERAN GEN STRUKTURAL, GEN NON-STRUKTURAL, DAN UNTRANSLATED REGION DALAM PERAKITAN VIRUS DENGUE

2015 ◽  
Vol 7 (2) ◽  
Author(s):  
Meiranty C. Pangerapan ◽  
Beivy J. Kolondam
Keyword(s):  
Aedes Aegypti ◽  
Dengue Virus ◽  
Dengue Fever ◽  
Aedes Albopictus ◽  
Untranslated Region ◽  
Rna Virus ◽  
Virus Genome ◽  
Interferon Response ◽  
Endoplasmic Reticulum Membrane ◽  
Structural Genes

Abstract: Dengue virus is a single-stranded RNA virus that belongs to Flaviviridae family. This virus causes dengue fever which is transmitted by Aedes aegypti dan Aedes albopictus. There are four serotypes of dengue virus; all of them can cause dengue fever. Understanding the genomics of dengue virus is important for research and diagnostics. The genome of dengue virus is 11 kilo-base long. It consists of 5’-untranslated region (5’-UTR), three structural genes (coding capsid protein, pre-membrane/membrane, and envelope), seven non-structural genes (coding NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5 proteins) and 3’-UTR. Non-structural genes are encoding proteins of viral RNA replication, interferon response, viral assembly and secretion, endoplasmic reticulum membrane invagination induction, immune-mediator induction, and RNA 5’-caping.Keywords: dengue virus, genome, structural genes, non-structural genes, untranslated region.Abstrak: Virus dengue merupakan virus RNA beruntai tunggal yang termasuk dalam famili Flaviviridae. Virus ini adalah penyebab penyakit demam berdarah dengue yang ditransmisikan melalui nyamuk Aedes aegypti dan Aedes albopictus. Ada empat serotipe virus dengue yang telah dikenal secara luas yang ada semuanya dapat menimbulkan penyakit demam berdarah. Pemahaman tentang genomik virus dengue sangat penting untuk pengembangan penelitian dan juga untuk keperluan diagnostik. Genom virus dengue memiliki panjang 11 kilo basa. Genomnya tersusun atas 5’-untranslated region (5’-UTR), tiga gen struktural (mengodekan protein kapsid, premembran/membran dan amplop), tujuh gen non-struktural (mengodekan protein NS1, NS2A, NS2B, NS3, NS4A, NS4B dan NS5) dan 3’-UTR. Gen-gen non-struktural mengodekan protein untuk replikasi RNA virus, respon interferon, perakitan, sekresi partikel virus, menginduksi invaginasi membran retikulum endoplasma, induksi imunomediator dan penambahan tudung pada ujung 5’ RNA.Kata kunci: virus dengue, genom, gen struktural, gen non-struktural, untranslated region

scholarly journals 2610. A Deadly Intrusion: Competitive Strain Displacement among Dengue Virus Strains in Sri lanka

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S907-S908
Author(s):  
Dylan C Gallegos ◽  
Stacy Rodriguez ◽  
Immo Hansen ◽  
Kathryn Hanley
Keyword(s):  
Sri Lanka ◽  
Dengue Virus ◽  
Virus Titer ◽  
Hemorrhagic Fever ◽  
T Test ◽  
Rnai Pathway ◽  
Argonaute 2 ◽  
Key Enzyme ◽  
Different Strains

Abstract Background Mosquito-borne dengue virus (DENV), the agent of dengue hemorrhagic fever (DHF), is genetically diverse, and new strains regularly invade distant locations and displace existing strains. Invasive strains often cause higher rates of DHF than displaced strains, so it is critical to identify the mechanisms that enable invasion. We tested the hypothesis that invasive strains are less susceptible to RNA interference (RNAi), the major antiviral defense in mosquitoes, than displaced strains. Methods We knocked-down (KD) RNAi in vivo in Aedes aegypti, the DENV vector, by injecting mosquitoes with double-stranded RNA against Argonaute 2 (Ago2), a key enzyme in the RNAi pathway, or a control dsRNA. Ago2 KD and control mosquitoes were fed bloodmeals containing 1 of 3 isolates each of 3 different strains of DENV that had undergone sequential competitive displacement in Sri Lanka, termed, in order of displacement, Pre-DHF, Post-DHF and Ultra-DHF. We predicted that the Pre-DHF strain, which we have previously shown to be less infectious for mosquitoes than the other two strains, would show a greater increase in infectivity than those strains. Engorged mosquitoes were incubated for 10 days, homogenized, and assayed for virus. Results Ago2 KD efficiency ranged from 79% to 98%, as determined by semi-quantitative PCR and band densitometry. The percentage of mosquitoes infected following Ago2 vs. control KD was not significantly different (33% vs. 47%; paired t-test, DF = 8, P = 0.08). However, among infected mosquitoes, virus titer was significantly higher in Ago2 KD mosquitoes (3.98 vs. 3.38 log10 plaque forming units/body; t-test, DF = 14, P = 0.02). Contra our prediction, a two-factor ANOVA did not reveal a significant interaction between the effect of virus strain and treatment (DF = 5, P = 0.58), indicating that Pre-DHF viruses did not show a larger response to Ago2 KD than Post and Ultra-DHF viruses. Conclusion These data support the role of RNAi as a key mosquito defense against virus replication in mosquitoes but indicate that the differences in competitive success among the 3 DENV strains studied are not due to differences in interactions with Ago2 during initial stages of mosquito infection. Disclosures All authors: No reported disclosures.

scholarly journals Analysis of the virus propagation profile of 14 dengue virus isolates in Aedes albopictus C6/36 cells

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Atitaya Hitakarun ◽  
Suwipa Ramphan ◽  
Nitwara Wikan ◽  
Duncan R. Smith
Keyword(s):  
Dengue Virus ◽  
Aedes Albopictus ◽  
Rna Virus ◽  
Strain Variation ◽  
Virus Propagation ◽  
Large Numbers ◽  
Specific Strain ◽  
Maximum Titer ◽  
Virus Genomes ◽  
Virus Isolates

Abstract Objective The mosquito transmitted RNA virus dengue virus (DENV) shows significant variation as a consequence of the lack of proofreading activity of the RNA-dependent RNA polymerase that synthesizes new virus genomes. How this variation affects DENV replication, and how this in turn impacts drug development remains largely unknown. Given the technical limitations in working with large numbers of isolates few studies have sought to investigate this area. This study used a panel of 14 DENV isolates of different serotypes and origins to determine how much virus replication in Aedes albopictus C6/36 cells was affected by DENV variability. Results The results showed that there was considerable variation, with peak titers ranging from 6Log10 to 8Log10, and maximum titer being reached from day 3 to day 9 post infection. While strains from DENV 1 and 4 serotypes showed considerable uniformity, DENV 2 and 3 strains showed much greater variation. Overall, these results show that serotype specific strain variation can have a significant impact on DENV replication, suggesting that studies either investigating DENV pathogenesis or developing drug therapeutics should consider the contribution of DENV variability.

scholarly journals Tilting the balance between RNA interference and replication eradicatesLeishmaniaRNA virus 1 and mitigates the inflammatory response

2016 ◽  
Vol 113 (43) ◽  
pp. 11998-12005 ◽  
Author(s):  
Erin A. Brettmann ◽  
Jahangheer S. Shaik ◽  
Haroun Zangger ◽  
Lon-Fye Lye ◽  
F. Matthew Kuhlmann ◽  
...  
Keyword(s):  
High Efficiency ◽  
Rna Virus ◽  
Rnai Pathway ◽  
Leishmania Braziliensis ◽  
Stem Loop ◽  
Mucocutaneous Leishmaniasis ◽  
Virus Retention ◽  
Dsrna Genome

ManyLeishmania(Viannia) parasites harbor the double-stranded RNA virusLeishmania RNA virus 1(LRV1), which has been associated with increased disease severity in animal models and humans and with drug treatment failures in humans. Remarkably, LRV1 survives in the presence of an active RNAi pathway, which in many organisms controls RNA viruses. We found significant levels (0.4 to 2.5%) of small RNAs derived from LRV1 in bothLeishmania braziliensisandLeishmania guyanensis, mapping across both strands and with properties consistent with Dicer-mediated cleavage of the dsRNA genome. LRV1 lackscis- ortrans-acting RNAi inhibitory activities, suggesting that virus retention must be maintained by a balance between RNAi activity and LRV1 replication. To tilt this balance toward elimination, we targeted LRV1 using long-hairpin/stem-loop constructs similar to those effective against chromosomal genes. LRV1 was completely eliminated, at high efficiency, accompanied by a massive overproduction of LRV1-specific siRNAs, representing as much as 87% of the total. For bothL. braziliensisandL. guyanensis, RNAi-derived LRV1-negative lines were no longer able to induce a Toll-like receptor 3–dependent hyperinflammatory cytokine response in infected macrophages. We demonstrate in vitro a role for LRV1 in virulence ofL. braziliensis, theLeishmaniaspecies responsible for the vast majority of mucocutaneous leishmaniasis cases. These findings establish a targeted method for elimination of LRV1, and potentially of otherLeishmaniaviruses, which will facilitate mechanistic dissection of the role of LRV1-mediated virulence. Moreover, our data establish a third paradigm for RNAi–viral relationships in evolution: one of balance rather than elimination.

scholarly journals Computational Identification of Dengue Virus MicroRNA-Like Structures and Their Cellular Targets

2014 ◽  
Vol 8 ◽  
pp. BBI.S13649 ◽  
Author(s):  
Maicol Ospina-Bedoya ◽  
Natalia Campillo-Pedroza ◽  
Juan P. Franco-Salazar ◽  
Juan C. Gallego-Gómez
Keyword(s):  
Dengue Virus ◽  
Messenger Rna ◽  
Noncoding Rna ◽  
Rna Virus ◽  
Mature Mirnas ◽  
Virus Genome ◽  
Support Vector ◽  
Direct Role ◽  
Cellular Targets ◽  
Small Noncoding Rna

MicroRNAs (miRNAs) are small, noncoding RNA molecules that regulate transcriptional and posttranscriptional gene regulation of the cell. Experimental evidence shows that miRNAs have a direct role in different cellular processes, such as immune function, apoptosis, and tumorigenesis. In a viral infection context, miRNAs have been connected with the interplay between host and pathogen, occupying a major role in pathogenesis. While numerous viral miRNAs from DNA viruses have been identified, characterization of functional RNA virus-encoded miRNAs and their potential targets is still ongoing. Here, we used an in silico approach to analyze dengue Virus genome sequences. Pre-miRNAs were extracted through VMir software, and the identification of putative pre-miRNAs and mature miRNAs was accessed using Support Vector Machine web tools. The targets were scanned using miRanda software and functionally annotated using ClueGo. Via computational tools, eight putative miRNAs were found to hybridize with numerous targets of morphogenesis, differentiation, migration, and growth pathways that may play a major role in the interaction of the virus and its host. Future approaches will focus on experimental validation of their presence and target messenger RNA genes to further elucidate their biological functions in human and mosquito cells.

scholarly journals Aedes anphevirus (AeAV): an insect-specific virus distributed worldwide inAedes aegyptimosquitoes that has complex interplays withWolbachiaand dengue virus infection in cells

2018 ◽  
Author(s):  
Rhys Parry ◽  
Sassan Asgari
Keyword(s):  
Dengue Virus ◽  
Cell Lines ◽  
Rna Viruses ◽  
Rna Virus ◽  
Asia Pacific ◽  
Mammalian Cell Lines ◽  
Persistent Virus ◽  
Specific Virus ◽  
Laboratory Colonies

AbstractInsect specific viruses (ISVs) of the yellow fever mosquitoAedes aegyptihave been demonstrated to modulate transmission of arboviruses such as dengue virus (DENV) and West Nile virus by the mosquito. The diversity and composition of the virome ofAe. aegypti, however, remains poorly understood. In this study, we characterised Aedes anphevirus (AeAV), a negative-sense RNA virus from the orderMononegavirales. AeAV identified fromAedescell lines were infectious to bothAe. aegyptiandAedes albopictuscells, but not to three mammalian cell lines. To understand the incidence and genetic diversity of AeAV, we assembled 17 coding-complete and two partial genomes of AeAV from available RNA-Seq data. AeAV appears to transmit vertically and be present in laboratory colonies, wild-caught mosquitoes and cell lines worldwide. Phylogenetic analysis of AeAV strains indicates that as theAe. aegyptimosquito has expanded into the Americas and Asia-Pacific, AeAV has evolved into monophyletic African, American and Asia-Pacific lineages. The endosymbiotic bacteriumWolbachia pipientisrestricts positive-sense RNA viruses inAe. aegypti. Re-analysis of a small RNA library ofAe. aegypticells co-infected with AeAV andWolbachiaproduces an abundant RNAi response consistent with persistent virus replication. We foundWolbachiaenhances replication of AeAV when compared to a tetracycline cleared cell line, and AeAV modestly reduces DENV replicationin vitro. The results from our study improve understanding of the diversity and evolution of the virome ofAe. aegyptiand adds to previous evidence that showsWolbachiadoes not restrict a range of negative strand RNA viruses.

scholarly journals IDENTIFICATION OF DENGUE VIRUS SEROTYPES AT THE DR. SOETOMO HOSPITAL SURABAYA IN 2016 AND ITS CORRELATION WITH NS1 ANTIGEN DETECTION

2018 ◽  
Vol 23 (2) ◽  
pp. 151
Author(s):  
Jeine Stela Akualing ◽  
Aryati Aryati ◽  
Puspa Wardhani ◽  
Usman Hadi
Keyword(s):  
Polymerase Chain Reaction ◽  
Dengue Virus ◽  
Reverse Transcriptase ◽  
Ribonucleic Acid ◽  
Rna Virus ◽  
Rt Pcr ◽  
Chain Reaction ◽  
Ns1 Antigen ◽  
Dengue Virus Serotypes ◽  
Polymerase Chain

Serotipe virus dengue yang beredar terus mengalami perubahan dan berbeda di setiap daerah. Pergeseran serotipe maupun genotipedi dalamnya, mempengaruhi terjadinya wabah dengue di berbagai negara. Perbedaan serotipe diduga bernasab dengan deteksi antigen(Ag) non-structural 1 (NS1), namun belum banyak penelitian yang mendukung hal tersebut. Penelitian potong lintang dikerjakan sejakFebruari-Agustus 2016 dan didapatkan 60 subjek infeksi virus dengue (IVD) dan 25 non-IVD. Ribonucleic acid (RNA) virus denguediperiksa di semua subjek menggunakan Simplexa Dengue Real-Time Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR)termasuk identifikasi serotipe virus dengue dan pemeriksaan NS1 menggunakan uji cepat NS1 Panbio. Perbedaan perbandingan variabelkategorikal dianalisis dengan uji Fisher Exact. Kenasaban antara serotipe dengan deteksi Ag NS1 dianalisis dengan Chi-Kuadrat. RNAvirus dengue terdeteksi di 43 dari 60 subjek IVD (71,7%). Serotipe terbanyak adalah DENV-3 (62,8%). Pergeseran dominasi serotipetelah terjadi di Surabaya, sebelumnya dari DENV-2 ke DENV-1 dan sekarang DENV-3, kemungkinan akibat mobilitas pejamu, transporvirus dan faktor geografis. Kepekaan uji cepat NS1 75% dan kekhasan 100%. Persentase deteksi NS1 antar serotipe berbeda bermakna(p=0,002). Deteksi NS1 lebih rendah pada DENV-1 dibandingkan DENV-2 (p=0,007) ataupun DENV-3 (p=0,003). Serotipe virusdengue bernasab dengan deteksi NS1 (p=0,005). Ciri serotipe maupun genotipe virus dengue kemungkinan mempengaruhi sekresiNS1. Telah terjadi pergeseran serotipe virus dengue di pasien IVD di Surabaya sehingga diperlukan surveillance berkesinambunganuntuk memperkirakan terjadinya wabah. Serotipe bernasab dengan deteksi NS1. Salah satu penyebab hasil negatif palsu NS1 adalahperbedaan serotipe.

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