Formation of Higher-Order Foot-and-Mouth Disease Virus 3D
            <sup>pol</sup>
            Complexes Is Dependent on Elongation Activity

Bentham, Matthew; Holmes, Kris; Forrest, Sophie; Rowlands, David J.; Stonehouse, Nicola J.

doi:10.1128/jvi.05696-11

Cited by 31 publications

(43 citation statements)

References 21 publications

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“…However, most studies suggest that inhibition of virus infection by aptamers targeting different viral proteins can be attributed to suppression of viral protein by the aptamers themselves (30)(31)(32)(33). Consistent with these reports, our study showed that the aptamers for core protein do not induce IFN-␤ and ISGs, indicating that inhibition of infectious virus production by core aptamers is not due to the innate immune response.…”

Section: Figsupporting

confidence: 80%

Inhibition of Hepatitis C Virus Production by Aptamers against the Core Protein

Shi

Gao

et al. 2014

J Virol

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bHepatitis C virus (HCV) core protein is essential for virus assembly. HCV core protein was expressed and purified. Aptamers against core protein were raised through the selective evolution of ligands by the exponential enrichment approach. Detection of HCV infection by core aptamers and the antiviral activities of aptamers were characterized. The mechanism of their anti-HCV activity was determined. The data showed that selected aptamers against core specifically recognize the recombinant core protein but also can detect serum samples from hepatitis C patients. Aptamers have no effect on HCV RNA replication in the infectious cell culture system. However, the aptamers inhibit the production of infectious virus particles. Beta interferon (IFN-␤) and interferon-stimulated genes (ISGs) are not induced in virally infected hepatocytes by aptamers. Domains I and II of core protein are involved in the inhibition of infectious virus production by the aptamers. V31A within core is the major resistance mutation identified. Further study shows that the aptamers disrupt the localization of core with lipid droplets and NS5A and perturb the association of core protein with viral RNA. The data suggest that aptamers against HCV core protein inhibit infectious virus production by disrupting the localization of core with lipid droplets and NS5A and preventing the association of core protein with viral RNA. The aptamers for core protein may be used to understand the mechanisms of virus assembly. Core-specific aptamers may hold promise for development as early diagnostic reagents and potential therapeutic agents for chronic hepatitis C.

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Section: Figsupporting

confidence: 80%

Inhibition of Hepatitis C Virus Production by Aptamers against the Core Protein

Shi

Gao

et al. 2014

J Virol

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“…This was one exceptional example because RIG-I aptamer was designed to have specific motifs to bind and activate RIG-I in this study. However, many studies suggest that inhibition of viral infection by aptamers targeting viral proteins is attributed to the suppression of the function of viral proteins by aptamers (33)(34)(35)(36). In accordance with these studies, our study showed that an aptamer for HCV E1E2 does not induce the expression of IFN-␤ and ISGs, indicating that inhibition of HCV infection by an E1E2-specific aptamer is not due to the innate immune response.…”

Section: Discussionsupporting

confidence: 77%

Inhibition of Hepatitis C Virus Infection by DNA Aptamer against Envelope Protein

Yang

Meng

et al. 2013

Antimicrob Agents Chemother

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c Hepatitis C virus (HCV) envelope protein (E1E2) is essential for virus binding to host cells. Aptamers have been demonstrated tohave strong promising applications in drug development. In the current study, a cDNA fragment encoding the entire E1E2 gene of HCV was cloned. E1E2 protein was expressed and purified. Aptamers for E1E2 were selected by the method of selective evolution of ligands by exponential enrichment (SELEX), and the antiviral actions of the aptamers were examined. The mechanism of their antiviral activity was investigated. The data show that selected aptamers for E1E2 specifically recognize the recombinant E1E2 protein and E1E2 protein from HCV-infected cells. CD81 protein blocks the binding of aptamer E1E2-6 to E1E2 protein. Aptamers against E1E2 inhibit HCV infection in an infectious cell culture system although they have no effect on HCV replication in a replicon cell line. Beta interferon (IFN-␤) and IFN-stimulated genes (ISGs) are not induced in virus-infected hepatocytes with aptamer treatment, suggesting that E1E2-specific aptamers do not induce innate immunity. E2 protein is essential for the inhibition of HCV infection by aptamer E1E2-6, and the aptamer binding sites are located in E2. Q412R within E1E2 is the major resistance substitution identified. The data indicate that an aptamer against E1E2 exerts its antiviral effects through inhibition of virus binding to host cells. Aptamers against E1E2 can be used with envelope protein to understand the mechanisms of HCV entry and fusion. The aptamers may hold promise for development as therapeutic drugs for hepatitis C patients. Hepatitis C virus (HCV) infects 3% of the world's population, and persistent virus infection causes chronic hepatitis, liver cirrhosis, and even hepatocellular carcinoma (1). There is no vaccine available, and alpha interferon (IFN-␣)-based therapy is the current treatment for patients with chronic hepatitis C (2). Many patients do not response to the therapy. There is an urgent need to develop well-tolerated and effective therapeutic drugs against HCV infection (3).HCV is an enveloped, single positive-strand RNA virus of the Flaviviridae family. The 9.6-kb viral genome encodes one polyprotein that is processed by viral and cellular proteases to produce structural proteins including core protein and envelope proteins E1 and E2 as well as the nonstructural proteins consisting of the p7 ion channel, NS2-3 protease, NS3 serine protease, RNA helicase, NS4A polypeptide, NS4B, NS5A proteins, and NS5B RNA-dependent RNA polymerase. E1 and E2 are type I membrane glycoproteins and form a noncovalent complex, which is believed to be the building block for the viral envelope (4). E2 is thought to be primarily responsible for receptor binding (5). Infection of the host cells by HCV is initiated through the interactions between the E1E2 protein and several previously identified HCV entry receptors, including CD81, scavenger receptor class B type I (SR-BI), claudin-1 (CLDN1), and occludin (OCLN) (6-9). The essential role of E1E2 i...

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“…These results showed that loop b9-a11 plays a central role in binding template RNA and accommodating the incoming nucleotide. Furthermore, very recent research has revealed that FMDV 3D pol forms a fibrillar replication lattice in the presence of all the components necessary for an elongation assay in vitro, which greatly enhances viral replication [16]. In conclusion, such structural analyses not only shed new light into the molecular basis of FMDV RNA replication but also provide effective information for the design of new FMDV 3D pol inhibitors.…”

Section: Non-structural Proteinsmentioning

confidence: 94%

“…These substrate-binding sites may be used for virtual screening, and the suitable ligands might act as effective inhibitors [109,147]. In addition, RNA aptamers to FMDV 3D pol are also potential inhibitors because they can prevent the formation of higher-order 3D pol complexes [16].…”

Section: Non-structural Proteinsmentioning

confidence: 99%

Three-dimensional structure of foot-and-mouth disease virus and its biological functions

2014

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Foot-and-mouth disease (FMD), an acute, violent, infectious disease of cloven-hoofed animals, remains widespread in most parts of the world. It can lead to a major plague of livestock and an economical catastrophe. Structural studies of FMD virus (FMDV) have greatly contributed to our understanding of the virus life cycle and provided new horizons for the control and eradication of FMDV. To examine host-FMDV interactions and viral pathogenesis from a structural perspective, the structures of viral structural and non-structural proteins are reviewed in the context of their relevance for virus assembly and dissociation, formation of capsid-like particles and virus-receptor complexes, and viral penetration and uncoating. Moreover, possibilities for devising novel antiviral treatments are discussed.

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Formation of Higher-Order Foot-and-Mouth Disease Virus 3D ^pol Complexes Is Dependent on Elongation Activity

Cited by 31 publications

References 21 publications

Inhibition of Hepatitis C Virus Production by Aptamers against the Core Protein

Inhibition of Hepatitis C Virus Production by Aptamers against the Core Protein

Inhibition of Hepatitis C Virus Infection by DNA Aptamer against Envelope Protein

Three-dimensional structure of foot-and-mouth disease virus and its biological functions

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Formation of Higher-Order Foot-and-Mouth Disease Virus 3D pol Complexes Is Dependent on Elongation Activity

Cited by 31 publications

References 21 publications

Inhibition of Hepatitis C Virus Production by Aptamers against the Core Protein

Inhibition of Hepatitis C Virus Production by Aptamers against the Core Protein

Inhibition of Hepatitis C Virus Infection by DNA Aptamer against Envelope Protein

Three-dimensional structure of foot-and-mouth disease virus and its biological functions

Contact Info

Product

Resources

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Formation of Higher-Order Foot-and-Mouth Disease Virus 3D ^pol Complexes Is Dependent on Elongation Activity