Analyses of SELEX-derived ZAP-binding RNA aptamers suggest that the binding specificity is determined by both structure and sequence of the RNA

Huang, Zhiqun; Wang, Xinlu; Gao, Guangxia

doi:10.1007/s13238-010-0096-9

Cited by 22 publications

(22 citation statements)

References 18 publications

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“…However, alignment of HBV ZRE with other individual viral ZREs did not reveal any obvious sequence homology (data not shown), suggesting that a mysterious secondary or tertiary RNA structure may define the common feature of ZRE. A recent SELEX (Systematic Evolution of Ligands by Exponential Enrichment) study showed that ZAP-binding aptamers that were 40-nt-long G-rich RNAs with stem-loop structures containing conserved “GGGUGG” and “GAGGG” motifs in the loop region [75]. Interestingly, HBV ZRE contains a stem-loop region (epsilon (ε), nt 1849–1909) which serves as the pgRNA encapsidation signal and as the priming template for virus reverse transcription [6], [7], [76].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Hepatitis B Virus Replication by the Host Zinc Finger Antiviral Protein

et al. 2013

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The zinc finger antiviral protein (ZAP) is a mammalian host restriction factor that inhibits the replication of a variety of RNA viruses, including retroviruses, alphaviruses and filoviruses, through interaction with the ZAP-responsive elements (ZRE) in viral RNA, and recruiting the exosome to degrade RNA substrate. Hepatitis B virus (HBV) is a pararetrovirus that replicates its genomic DNA via reverse transcription of a viral pregenomic (pg) RNA precursor. Here, we demonstrate that the two isoforms of human ZAP (hZAP-L and -S) inhibit HBV replication in human hepatocyte-derived cells through posttranscriptional down-regulation of viral pgRNA. Mechanistically, the zinc finger motif-containing N-terminus of hZAP is responsible for the reduction of HBV RNA, and the integrity of the four zinc finger motifs is essential for ZAP to bind to HBV RNA and fulfill its antiviral function. The ZRE sequences conferring the susceptibility of viral RNA to ZAP-mediated RNA decay were mapped to the terminal redundant region (nt 1820–1918) of HBV pgRNA. In agreement with its role as a host restriction factor and as an innate immune mediator for HBV infection, ZAP was upregulated in cultured primary human hepatocytes and hepatocyte-derived cells upon IFN-α treatment or IPS-1 activation, and in the livers of hepatitis B patients during immune active phase. Knock down of ZAP expression increased the level of HBV RNA and partially attenuated the antiviral effect elicited by IPS-1 in cell cultures. In summary, we demonstrated that ZAP is an intrinsic host antiviral factor with activity against HBV through down-regulation of viral RNA, and that ZAP plays a role in the innate control of HBV replication. Our findings thus shed light on virus-host interaction, viral pathogenesis, and antiviral approaches.

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Section: Discussionmentioning

confidence: 99%

Inhibition of Hepatitis B Virus Replication by the Host Zinc Finger Antiviral Protein

et al. 2013

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“…In 2010, Huang et al investigated aptamers capable of bind zinc-finger antiviral protein responsible for, inter alia, inhibition of Ebola virus replication. Selected aptamers contained conserved sequences “GGGUGG” and “GAGGG” in the loop region, which was important for specific interaction between aptamer and antiviral protein [ 111 ]. This information could serve as a base to design molecular diagnostic tests capable to detect Ebola mRNA.…”

Section: Aptamers Against Ebola Infectionmentioning

confidence: 99%

Aptamers in Diagnostics and Treatment of Viral Infections

Wandtke

Woźniak

Kopiński

2015

Viruses

114

109

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Aptamers are in vitro selected DNA or RNA molecules that are capable of binding a wide range of nucleic and non-nucleic acid molecules with high affinity and specificity. They have been conducted through the process known as SELEX (Systematic Evolution of Ligands by Exponential Enrichment). It serves to reach specificity and considerable affinity to target molecules, including those of viral origin, both proteins and nucleic acids. Properties of aptamers allow detecting virus infected cells or viruses themselves and make them competitive to monoclonal antibodies. Specific aptamers can be used to interfere in each stage of the viral replication cycle and also inhibit its penetration into cells. Many current studies have reported possible application of aptamers as a treatment or diagnostic tool in viral infections, e.g., HIV (Human Immunodeficiency Virus), HBV (Hepatitis B Virus), HCV (Hepatitis C Virus), SARS (Severe Acute Respiratory Syndrome), H5N1 avian influenza and recently spread Ebola. This review presents current developments of using aptamers in the diagnostics and treatment of viral diseases.

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“…With the aim to identify RNA sequences that could be a target of ZAP, Huang et al used aptamer technology identifying G-rich RNA aptamers that contained conserved “GGGUGG” and “GAGGG” motifs in the loop region. Interestingly, overexpression of the aptamers significantly reduced ZAP’s antiviral activity and the substitution of the conserved motifs of the aptamers significantly impaired their ZAP-binding ability and ZAP-antagonizing activity, suggesting that the RNA sequence is important for specific interaction between ZAP and the target RNA [188]. …”

Section: Aptamers For Virus Diagnosis and Treatmentmentioning

confidence: 99%

Use of Aptamers as Diagnostics Tools and Antiviral Agents for Human Viruses

González

Martı́n

Fernández³

et al. 2016

Pharmaceuticals

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Appropriate diagnosis is the key factor for treatment of viral diseases. Time is the most important factor in rapidly developing and epidemiologically dangerous diseases, such as influenza, Ebola and SARS. Chronic viral diseases such as HIV-1 or HCV are asymptomatic or oligosymptomatic and the therapeutic success mainly depends on early detection of the infective agent. Over the last years, aptamer technology has been used in a wide range of diagnostic and therapeutic applications and, concretely, several strategies are currently being explored using aptamers against virus proteins. From a diagnostics point of view, aptamers are being designed as a bio-recognition element in diagnostic systems to detect viral proteins either in the blood (serum or plasma) or into infected cells. Another potential use of aptamers is for therapeutics of viral infections, interfering in the interaction between the virus and the host using aptamers targeting host-cell matrix receptors, or attacking the virus intracellularly, targeting proteins implicated in the viral replication cycle. In this paper, we review how aptamers working against viral proteins are discovered, with a focus on recent advances that improve the aptamers’ properties as a real tool for viral infection detection and treatment.

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Analyses of SELEX-derived ZAP-binding RNA aptamers suggest that the binding specificity is determined by both structure and sequence of the RNA

Cited by 22 publications

References 18 publications

Inhibition of Hepatitis B Virus Replication by the Host Zinc Finger Antiviral Protein

Inhibition of Hepatitis B Virus Replication by the Host Zinc Finger Antiviral Protein

Aptamers in Diagnostics and Treatment of Viral Infections

Use of Aptamers as Diagnostics Tools and Antiviral Agents for Human Viruses

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