3′
            <i>cis</i>
            -Acting Elements That Contribute to the Competence and Efficiency of Japanese Encephalitis Virus Genome Replication: Functional Importance of Sequence Duplications, Deletions, and Substitutions

Yun, Sijung; Choi, Yu‐Jeong; Song, Beom-Heon; Lee, Young-Min

doi:10.1128/jvi.02541-08

Cited by 45 publications

(42 citation statements)

References 83 publications

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“…To further examine whether another positive-strand RNA virus could increase Pin1 expression, we investigated JEV-infected BHK cells. The JEV infection was confirmed by immunoblot analysis using a rabbit anti-JEV NS1 antibody (36). However, JEV infection did not increase Pin1 expression (data not shown), indicating that this phenomenon was HCV specific.…”

Section: Resultsmentioning

confidence: 86%

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Peptidyl-Prolyl Isomerase Pin1 Is a Cellular Factor Required for Hepatitis C Virus Propagation

Lim

Tran

Park

et al. 2011

J Virol

117

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Section: Resultsmentioning

confidence: 86%

“…BHK-21 cells were either mock infected or infected with Japanese encephalitis virus (JEV) as described previously (36). Equal amounts of total-cell lysates harvested at either 24 h or 48 h were analyzed for JEV protein expression by immunoblotting with the rabbit anti-JEV NS1 antibody as described above.…”

mentioning

confidence: 99%

Peptidyl-Prolyl Isomerase Pin1 Is a Cellular Factor Required for Hepatitis C Virus Propagation

Lim

Tran

Park

et al. 2011

J Virol

117

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“…A schematic overview of the predicted 5Ј-3Ј panhandle and the HP-3ЈSL structure at the 3Ј terminus of WNV (6), DENV (8,9,12,13), yellow fever virus (YFV) (8,9,13), and Japanese encephalitis virus (JEV) (9,20) is shown in Fig. 4.…”

Section: Fig 3 Wnv 5ј-3ј Dar Complementarity Is Necessary For Efficmentioning

confidence: 99%

The 5′ and 3′ Downstream AUG Region Elements Are Required for Mosquito-Borne Flavivirus RNA Replication

Friebe

Shi

Harris

2011

J Virol

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Flaviviruses require complementarity between the 5 and 3 ends of the genome for RNA replication. For mosquito-borne flaviviruses, the cyclization sequences (CS) and upstream of AUG region (UAR) elements at the genomic termini are necessary for viral RNA replication, and a third motif, the downstream of AUG region (DAR), was recently designated for dengue virus. The 3 DAR sequence is also part of a hairpin (HP-3SL), and both complementarity between 5 and 3 DAR motifs and formation of the HP-3SL in the absence of the 5 end are conserved among mosquito-borne flaviviruses. Using West Nile virus as a model, we demonstrate that 5-3 DAR complementarity and HP-3SL formation are essential for viral RNA replication.Flaviviruses have an approximately 11-kb-long RNA genome of positive polarity (see reference 10). The viral RNA encodes one open reading frame (ORF), and the resulting polyprotein is cleaved co-and posttranslationally into 3 structural (N-terminal) and 7 nonstructural (NS) (C-terminal) proteins. The ORF is flanked on both sites by untranslated regions (5Ј and 3Ј UTR), which contain several cis-acting RNA elements that regulate RNA translation and replication. A prerequisite for viral RNA replication is genome circularization, and two essential sequence motifs complementary between the 5Ј and 3Ј ends have been reported for mosquito-borne flaviviruses: the 5Ј-3Ј cyclization sequences (CS) and 5Ј-3Ј upstream of AUG region (UAR) elements (1-3, 8, 9, 14, 16-19, 22, 23). Recently, a third motif in the dengue virus (DENV) 5Ј terminus, located downstream of the AUG region (DAR), was reported to be involved in RNA replication (7) and possibly genome circularization. The sequence at the 3Ј genomic end complementary to the 5Ј DAR motif (3Ј DAR) also appeared to have a role in RNA replication, but the data were less conclusive than that for the 5Ј DAR. Furthermore, the 3Ј DAR sequence is involved in the formation of a small hairpin at the bottom of the 3Ј stem-loop (HP-3ЈSL) in the absence of the 5Ј end, and nucleotides within the loop of the HP-3ЈSL are further predicted to form a pseudoknot with nucleotides in the 3ЈSL (13). Although it has been implicated in DENV translation (4) and replication (1,7,21), the role of the HP-3ЈSL in flavivirus replication has not been definitely delineated.To further define the role of the DAR sequences and the HP-3ЈSL in RNA replication of mosquito-borne flaviviruses, we used West Nile virus (WNV) as a model, since to date nothing has been definitively determined about the impact of either of these motifs in WNV RNA replication. To study the effect of the 5Ј DAR sequence on RNA replication, we modified a previously described WNV replicon (Fig. 1A [RlucRep]) in which the structural proteins were replaced by the gene encoding Renilla luciferase (11). This resulted in WNV-EMCV-Rep and WNV-SPACER-EMCV-Rep (Fig. 1A), which have an overall design analogous to that of DENV replicons 5ЈUTR-Cap-tr and 5ЈUTR-Cap-tr-SPACER (7). In the case of WNV, the 5Ј UTR and the first 93 capsid-coding nucleoti...

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“…Flavivirus UTRs are involved in translation and initiation of RNA replication and likely determine genome packaging (13,14,16,21,30,(39)(40)(41). Both the 5Ј UTR (ϳ100 nucleotides [nt] in size) and the 3Ј UTR (from ϳ400 to 700 nucleotides) can form secondary and tertiary structures which are highly conserved among mosquito-borne flaviviruses (1,8,10,14,29,32,34).…”

mentioning

confidence: 99%

“…Generally, a progressive negative effect on viral growth was shown with progressive deletions into the 3Ј-proximal region of the JEV 3Ј UTR (41). However, only a relatively short region of the JEV 3Ј UTR, consisting of the 3Ј-terminal 193 nt, was shown to be absolutely essential for gRNA replication (41).…”

mentioning

confidence: 99%

RNA Structures Required for Production of Subgenomic Flavivirus RNA

Funk

Truong

Nagasaki

et al. 2010

J Virol

198

282

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Flaviviruses are a group of single-stranded, positive-sense RNA viruses causing ϳ100 million infections per year. We have recently shown that flaviviruses produce a unique, small, noncoding RNA (ϳ0.5 kb) derived from the 3 untranslated region (UTR) of the genomic RNA (gRNA), which is required for flavivirus-induced cytopathicity and pathogenicity (G. P. Pijlman et al., Cell Host Microbe, 4: 579-591, 2008). This RNA (subgenomic flavivirus RNA [sfRNA]) is a product of incomplete degradation of gRNA presumably by the cellular 5-3 exoribonuclease XRN1, which stalls on the rigid secondary structure stem-loop II (SL-II) located at the beginning of the 3 UTR. Mutations or deletions of various secondary structures in the 3 UTR resulted in the loss of full-length sfRNA (sfRNA1) and production of smaller and less abundant sfRNAs (sfRNA2 and sfRNA3). Here, we investigated in detail the importance of West Nile virus Kunjin (WNV KUN ) 3 UTR secondary structures as well as tertiary interactions for sfRNA formation. We show that secondary structures SL-IV and dumbbell 1 (DB1) downstream of SL-II are able to prevent further degradation of gRNA when the SL-II structure is deleted, leading to production of sfRNA2 and sfRNA3, respectively. We also show that a number of pseudoknot (PK) interactions, in particular PK1 stabilizing SL-II and PK3 stabilizing DB1, are required for protection of gRNA from nuclease degradation and production of sfRNA. Our results show that PK interactions play a vital role in the production of nuclease-resistant sfRNA, which is essential for viral cytopathicity in cells and pathogenicity in mice.Arthropod-borne flaviviruses such as West Nile virus (WNV), dengue virus (DENV), and Japanese encephalitis virus (JEV) cause major outbreaks of potentially fatal disease and affect over 50 million people every year. The highly pathogenic North American strain of WNV (WNV NY99 ) has already claimed more than 1,000 lives with over 27,000 cases reported since its emergence in New York in 1999 and has raised global public health concerns (9). In contrast, the closely related Australian strain of WNV, WNV KUN , is highly attenuated and does not cause overt disease in humans and animals (11). WNV KUN has been used extensively as a model virus to study flavivirus replication and flavivirus-host interactions (13, 14, 16-19, 26, 38, 39).The ϳ11-kb positive-stranded, capped WNV genomic RNA (gRNA) lacks a poly(A) tail and consists of 5Ј and 3Ј untranslated regions (UTRs) flanking one open reading frame, which encodes the viral proteins required for the viral life cycle (6,15,38,39). Flavivirus UTRs are involved in translation and initiation of RNA replication and likely determine genome packaging (13,14,16,21,30,(39)(40)(41). Both the 5Ј UTR (ϳ100 nucleotides [nt] in size) and the 3Ј UTR (from ϳ400 to 700 nucleotides) can form secondary and tertiary structures which are highly conserved among mosquito-borne flaviviruses (1,8,10,14,29,32,34). More specifically, the WNV KUN 3Ј UTR consists of several conserved regions and se...

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3′ cis -Acting Elements That Contribute to the Competence and Efficiency of Japanese Encephalitis Virus Genome Replication: Functional Importance of Sequence Duplications, Deletions, and Substitutions

Cited by 45 publications

References 83 publications

Peptidyl-Prolyl Isomerase Pin1 Is a Cellular Factor Required for Hepatitis C Virus Propagation

Peptidyl-Prolyl Isomerase Pin1 Is a Cellular Factor Required for Hepatitis C Virus Propagation

The 5′ and 3′ Downstream AUG Region Elements Are Required for Mosquito-Borne Flavivirus RNA Replication

RNA Structures Required for Production of Subgenomic Flavivirus RNA

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