DEAD-box RNA helicase DDX3X inhibits DENV replication via regulating type one interferon pathway

Li, Guanghao; Feng, Tingting; Pan, Wen; Shi, Xia; Dai, Jianfeng

doi:10.1016/j.bbrc.2014.11.080

Cited by 54 publications

(40 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to its involvement in protein translation, the cell cycle, apoptosis, nuclear export, and eukaryotic gene regulation, human DDX3X is a critical molecule in in- nate immune signaling pathways and contributes to type I interferon (IFN) induction. A previous report showed that DDX3X is upregulated upon dengue virus (DENV) or porcine reproductive and respiratory syndrome virus (PRRSV) infection (27,28). However, contrary to our expectations, Western blotting showed no change in DDX3X protein levels in Huh7 cells upon HCoV-OC43-WT infection (Fig.…”

Section: Suitability Of Roc43-ns2delrluc For High-throughput Antiviracontrasting

confidence: 96%

Safe and Sensitive Antiviral Screening Platform Based on Recombinant Human Coronavirus OC43 Expressing the Luciferase Reporter Gene

Shen

Yang

et al. 2016

Antimicrob Agents Chemother

View full text Add to dashboard Cite

bHuman coronaviruses (HCoVs) cause 15 to 30% of mild upper respiratory tract infections. However, no specific antiviral drugs are available to prevent or treat HCoV infections to date. Here, we developed four infectious recombinant HCoVs-OC43 (rHCoVs-OC43) which express the Renilla luciferase (Rluc) reporter gene. Among these four rHCoVs-OC43, rOC43-ns2DelRluc (generated by replacing ns2 with the Rluc gene) showed robust luciferase activity with only a slight impact on its growth characteristics. Additionally, this recombinant virus remained stable for at least 10 passages in BHK-21 cells. rOC43-ns2DelRluc was comparable to its parental wild-type virus (HCoV-OC43-WT) with respect to the quantity of the antiviral activity of chloroquine and ribavirin. We showed that chloroquine strongly inhibited HCoV-OC43 replication in vitro, with a 50% inhibitory concentration (IC 50 ) of 0.33 M. However, ribavirin showed inhibition of HCoV-OC43 replication only at high concentrations which may not be applicable to humans in clinical treatment, with an IC 50 of 10 M. Furthermore, using a luciferase-based small interfering RNA (siRNA) screening assay, we identified double-stranded-RNA-activated protein kinase (PKR) and DEAD box RNA helicases (DDX3X) that exhibited antiviral activities, which were further verified by the use of HCoV-OC43-WT. Therefore, rOC43-ns2DelRluc represents a promising safe and sensitive platform for high-throughput antiviral screening and quantitative analysis of viral replication.

show abstract

Section: Suitability Of Roc43-ns2delrluc For High-throughput Antiviracontrasting

confidence: 96%

Safe and Sensitive Antiviral Screening Platform Based on Recombinant Human Coronavirus OC43 Expressing the Luciferase Reporter Gene

Shen

Yang

et al. 2016

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…The pathway involved with mRNA surveillance was remarkably activated (Figure 6D), and multiple genes belonging to the DExD/H box helicase family participated in host cellular responses against HTNV infection (Figure 6E). The DExD/H box helicases play vital roles in RNA metabolism, and some of these helicases can regulate host IFN responses and inhibit viral infection (Li et al, 2015; Diot et al, 2016). DGE analysis indicated that DDX3, DDX5, DDX6, DDX21, DDX50, and DDX60 were upregulated by HTNV (Figure 7A).…”

Section: Resultsmentioning

confidence: 99%

In-Cell Western Assays to Evaluate Hantaan Virus Replication as a Novel Approach to Screen Antiviral Molecules and Detect Neutralizing Antibody Titers

Chen

et al. 2017

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Hantaviruses encompass rodent-borne zoonotic pathogens that cause severe hemorrhagic fever disease with high mortality rates in humans. Detection of infectious virus titer lays a solid foundation for virology and immunology researches. Canonical methods to assess viral titers rely on visible cytopathic effects (CPE), but Hantaan virus (HTNV, the prototype hantavirus) maintains a relatively sluggish life cycle and does not produce CPE in cell culture. Here, an in-cell Western (ICW) assay was utilized to rapidly measure the expression of viral proteins in infected cells and to establish a novel approach to detect viral titers. Compared with classical approaches, the ICW assay is accurate and time- and cost-effective. Furthermore, the ICW assay provided a high-throughput platform to screen and identify antiviral molecules. Potential antiviral roles of several DExD/H box helicase family members were investigated using the ICW assay, and the results indicated that DDX21 and DDX60 reinforced IFN responses and exerted anti-hantaviral effects, whereas DDX50 probably promoted HTNV replication. Additionally, the ICW assay was also applied to assess NAb titers in patients and vaccine recipients. Patients with prompt production of NAbs tended to have favorable disease outcomes. Modest NAb titers were found in vaccinees, indicating that current vaccines still require improvements as they cannot prime host humoral immunity with high efficiency. Taken together, our results indicate that the use of the ICW assay to evaluate non-CPE Hantaan virus titer demonstrates a significant improvement over current infectivity approaches and a novel technique to screen antiviral molecules and detect NAb efficacies.

show abstract

“…Among the predicted ZIKV interacting proteins, SND1 and DDX3X interact with dengue virus RNA directly (34,35), FMRP expression is upregulated by the invasion of tick-borne encephalitis virus (36), ELAVL1 and IGF2BP1 are critical factors in HCV replication (37,38), and CPSF6 and TARDBP are involved in the life cycle of HIV (38,39). The list also includes a few stress granule related proteins, IGF2BP1, IGF2BP3 and ELAVL1 ( Figure 6A) (40,41).…”

Section: Prediction Of Host Factors That Bind To Zikv Rnamentioning

confidence: 99%

Integrative analysis of Zika virus genome RNA structure reveals critical determinants of viral infectivity

Zhang

Pan

Wei

et al. 2018

Preprint

Self Cite

View full text Add to dashboard Cite

Running title: RNA secondary structure regulates Zika virus infection SUMMARY Since its outbreak in 2007, Zika virus (ZIKV) has become a global health threat that causes severe neurological conditions. Here we perform a comparative in vivo structural analysis of the RNA genomes of two ZIKV strains to decipher the regulation of their infection at the RNA level. Our analysis identified both known and novel functional RNA structural elements. We discovered a functional long-range intramolecular interaction specific for the Asian epidemic strains, which contributes to their infectivity. Further, we developed a computational screening strategy that uses our RNA structural information to accurately predict host factors of ZIKV. We validated the predicted binding of the host protein ELAVL1 to ZIKV and showed that it promotes infection. Our findings illuminate the structural basis of ZIKV regulation and provide a rich resource for the discovery of RNA structural elements and host factors that are important for ZIKV infection. HIGHLIGHTS l Integrative probing in vivo generates comprehensive structural maps of ZIKV RNA genomes in infected cells l Comparative analysis revealed known and novel functional RNA structural elements in ZIKV genomes l A long-range intramolecular interaction specific for the epidemic Asian ZIKV strains affects infectivity in cell lines l Structural-based computational screening accurately predicts the RBP host factors of ZIKV in mammalian cells l The host protein ELAVL1 binds to ZIKV RNA and promotes viral infection

show abstract

DEAD-box RNA helicase DDX3X inhibits DENV replication via regulating type one interferon pathway

Cited by 54 publications

References 40 publications

Safe and Sensitive Antiviral Screening Platform Based on Recombinant Human Coronavirus OC43 Expressing the Luciferase Reporter Gene

Safe and Sensitive Antiviral Screening Platform Based on Recombinant Human Coronavirus OC43 Expressing the Luciferase Reporter Gene

In-Cell Western Assays to Evaluate Hantaan Virus Replication as a Novel Approach to Screen Antiviral Molecules and Detect Neutralizing Antibody Titers

Integrative analysis of Zika virus genome RNA structure reveals critical determinants of viral infectivity

Contact Info

Product

Resources

About