Hepatitis C virus genomic RNA dimerization is mediated via a kissing complex intermediate

Shetty, Sumangala; Kim, Seungtaek; Shimakami, Tetsuro; Lemon, Stanley M.; Mihailescu, Mihaela‐Rita

doi:10.1261/rna.1960410

Cited by 65 publications

(121 citation statements)

References 59 publications

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“…In another work, the authors showed that the RNA dimerization would be mediated via a kissing complex intermediate between two structurally rearranged DLS. The core protein would then stabilize the resulting extended duplex (Shetty et al 2010). Our results show that the minimal structured motif of the 3 ′ UTR containing the dimer linkage sequence SL2 is able to dimerize in vitro in the absence of any added protein.…”

Section: Discussionmentioning

confidence: 81%

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Direct evidence for RNA–RNA interactions at the 3′ end of the Hepatitis C virus genome using surface plasmon resonance

Palau

Masante

Ventura

et al. 2013

RNA

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Surface plasmon resonance was used to investigate two previously described interactions analyzed by reverse genetics and complementation mutation experiments, involving 5BSL3.2, a stem-loop located in the NS5B coding region of HCV. 5BSL3.2 was immobilized on a sensor chip by streptavidin-biotin coupling, and its interaction either with the SL2 stem-loop of the 3 ′ end or with an upstream sequence centered on nucleotide 9110 (referred to as Seq9110) was monitored in real-time. In contrast with previous results obtained by NMR assays with the same short RNA sequences that we used or SHAPE analysis with longer RNAs, we demonstrate that recognition between 5BSL3.2 and SL2 can occur in solution through a kissing-loop interaction. We show that recognition between Seq9110 and the internal loop of 5BSL3.2 does not prevent binding of SL2 on the apical loop of 5BSL3.2 and does not influence the rate constants of the SL2-5BSL3.2 complex. Therefore, the two binding sites of 5BSL3.2, the apical and internal loops, are structurally independent and both interactions can coexist. We finally show that the stem-loop SL2 is a highly dynamic RNA motif that fluctuates between at least two conformations: One is able to hybridize with 5BSL3.2 through loop-loop interaction, and the other one is capable of self-associating in the absence of protein, reinforcing the hypothesis of SL2 being a dimerization sequence. This result suggests also that the conformational dynamics of SL2 could play a crucial role for controlling the destiny of the genomic RNA.

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Section: Discussionmentioning

confidence: 81%

“…Previous works suggested that SL2 could be responsible for the dimerization of the viral RNA (Ivanyi-Nagy et al 2006;Shetty et al 2010). The results obtained with SL2 also prompted us to further investigate this stem-loop structure that displays a palindromic sequence.…”

Section: Self-association Of Sl2mentioning

confidence: 90%

Direct evidence for RNA–RNA interactions at the 3′ end of the Hepatitis C virus genome using surface plasmon resonance

Palau

Masante

Ventura

et al. 2013

RNA

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“…Formation of the terminal 3 ′ SLI and the known upstream stem-loop that includes the dimer linkage sequence (DLS) ( Fig. 4A; Ivanyi-Nagy et al 2006;Shetty et al 2010 . Alignment based secondary structures of the X-tail using sequences of 19 isolates.…”

Section: X-tailmentioning

confidence: 99%

“…In an alternative conformation of the X-tail, only two stem-loops are formed. Here, SLI remains the same, but SLII and SLIII are merged to form a single stemloop which includes a so-called dimerization linkage sequence (DLS) in its apical loop that was proposed to be necessary for viral RNA genome dimerization and possibly for genome encapsidation (Ivanyi-Nagy et al 2006;Shetty et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Conserved RNA secondary structures and long-range interactions in hepatitis C viruses

Fricke

Dünnes

Zayas

et al. 2015

RNA

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Hepatitis C virus (HCV) is a hepatotropic virus with a plus-strand RNA genome of ∼9.600 nt. Due to error-prone replication by its RNA-dependent RNA polymerase (RdRp) residing in nonstructural protein 5B (NS5B), HCV isolates are grouped into seven genotypes with several subtypes. By using whole-genome sequences of 106 HCV isolates and secondary structure alignments of the plus-strand genome and its minus-strand replication intermediate, we established refined secondary structures of the 5 ′ untranslated region (UTR), the cis-acting replication element (CRE) in NS5B, and the 3 ′ UTR. We propose an alternative structure in the 5 ′ UTR, conserved secondary structures of 5B stem-loop (SL)1 and 5BSL2, and four possible structures of the X-tail at the very 3 ′ end of the HCV genome. We predict several previously unknown long-range interactions, most importantly a possible circularization interaction between distinct elements in the 5 ′ and 3 ′ UTR, reminiscent of the cyclization elements of the related flaviviruses. Based on analogy to these viruses, we propose that the 5 ′ -3 ′ UTR base-pairing in the HCV genome might play an important role in viral RNA replication. These results may have important implications for our understanding of the nature of the cis-acting RNA elements in the HCV genome and their possible role in regulating the mutually exclusive processes of viral RNA translation and replication.

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“…HCV is a single stranded positive sense RNA virus belongs to the genus hepacivirus of Flaviviridae family [1]. It has a single open reading genome of ~9.6 kb, encoding a polypeptide of 3010 amino acids, flanked by untranslated region at both 5ʹ and 3ʹ terminus [2].…”

Section: Introductionmentioning

confidence: 99%

Molecular prevalence of hepatitis C virus genotypes in district Kohat, Khyber Pakhtunkhwa, Pakistan

Ullah

Ali

et al. 2017

PAB

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Hepatitis C Virus is a causative agents of liver cirrhosis, having highly diversified genome. Genotype study has important role in clinical setup and prognosis of hepatitis C virus infection. The aim of this was to investigate the prevalence and risk factors associated with hepatitis C virus genotypes in district Kohat, Khyber Pakhtunkhwa, Pakistan. Hepatitis C virus pre-infected patients (n = 600) were analyzed to assess circulating HCV genotypes, using reverse transcriptase approach. Moreover serum ALT levels were determined followed by correlation with genotypes. In current study cohort, majority of patients (62%) were, having elevated ALT (> 50 U/L). similarly patients with mixed HCV genotypes, 3a/3b have relatively higher ALT levels (~62) compared to 2a/3a (~43) and others. We found significant correlation (p = 0.002) of genotype 2a in connection with ALT (49.48) level. Similarly 3a, 3b, mixed as well as untypeable genotypes correlations were also found highly significant (p <0.001) with their mean ALT levels (47.14, 31.58, 46.69 and 43.68) respectively. In our studied population, most prevalent genotypes were 3a (25%) followed by 3b (20%) and 2a (15%). Fifteen percent of patient's infections were untypeable while in 10% patients mixed genotype were observed. Among total 30 (5%) were blood transfusion cases, 90(15%) surgical, 540 (90%) dentistry, 360 (60%) Barber, 492 (82%) Pricks, whereas 180 (30%) cases were those having early type of HCV/HBV infection in their family. In current study, genotypes 3a and 3b were more prevalent, with two potential risk factors; dentistry and barbers. Moreover, genotypes and ALT investigations were found to be more fruitful in prognosis as well as management of HCV infection.

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Hepatitis C virus genomic RNA dimerization is mediated via a kissing complex intermediate

Cited by 65 publications

References 59 publications

Direct evidence for RNA–RNA interactions at the 3′ end of the Hepatitis C virus genome using surface plasmon resonance

Direct evidence for RNA–RNA interactions at the 3′ end of the Hepatitis C virus genome using surface plasmon resonance

Conserved RNA secondary structures and long-range interactions in hepatitis C viruses

Molecular prevalence of hepatitis C virus genotypes in district Kohat, Khyber Pakhtunkhwa, Pakistan

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