Interferon   expressed by a recombinant respiratory syncytial virus attenuates virus replication in mice without compromising immunogenicity

HRSV (human respiratory syncytial virus) is a serious cause of lower respiratory tract illness in infants and young children. Designing inhibitors from the proteins involved in virus replication and infection process provides target for new therapeutic treatments. In the present study,in silicodocking was performed using motavizumab as a template to design motavizumab derived oligopeptides for developing novel anti-HRSV agents. Additional simulations were conducted to study the conformational propensities of the oligopeptides and confirmed the hypothesis that the designed oligopeptide is highly flexible and capable of assuming stable confirmation. Our study demonstrated the best specific interaction of GEKKLVEAPKS oligopeptide for glycoprotein strain A among various screened oligopeptides. Encouraged by the results, we expect that the proposed scheme will provide rational choices for antibody reengineering which is useful for systematically identifying the possible ways to improve efficacy of existing antibody drugs.

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2-5A-DNA conjugate inhibition of respiratory syncytial virus replication: effects of oligonucleotide structure modifications and RNA target site selection

Antiviral Research ◽

10.1016/s0166-3542(99)00005-4 ◽

1999 ◽

Vol 41 (3) ◽

pp. 119-134 ◽

Cited By ~ 22

Author(s):

D.L Barnard ◽

R.W Sidwell ◽

W Xiao ◽

M.R Player ◽

S.A Adah ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Virus Replication ◽

Site Selection ◽

Target Site ◽

Target Site Selection ◽

Syncytial Virus

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Luteolin Inhibits Respiratory Syncytial Virus Replication by Regulating the MiR-155/SOCS1/STAT1 Signaling Pathway

10.21203/rs.3.rs-23615/v2 ◽

2020 ◽

Author(s):

Saisai Wang ◽

Yiting Ling ◽

Yuanyuan Yao ◽

Gang Zheng ◽

Wenbin Chen

Keyword(s):

Respiratory Syncytial Virus ◽

Signaling Pathway ◽

Western Blotting ◽

Virus Replication ◽

Janus Kinase ◽

Luciferase Assay ◽

Luciferase Reporter ◽

Cytokine Signaling ◽

Stat1 Signaling ◽

Syncytial Virus

Abstract Background: Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infection in infants, children, immunocompromised adults, and elderly individuals. Currently, there are few therapeutic options available to prevent RSV infection. The present study aimed to investigate the effects of luteolin on RSV replication and the related mechanisms. Material and methods: We pretreated cells and mice with luteolin before infection with RSV, the virus titer, expressions of RSV-F, interferon (IFN)-stimulated genes (ISGs), and production of IFN-α and IFN-β were determined by plaque assay, RT-qPCR, and ELISA, respectively. The activation of Janus kinase (JAK)-signal transducer and activator of transcription 1 (STAT1) signaling pathway was detected by Western blotting and luciferase assay. Proteins which negatively regulates STAT1 was determined by Western blotting. Then cells were transfected with suppressor of cytokine signaling 1 (SOCS1) plasmid and virus replication and ISGs expression was determined. Luciferase reporter assay and Western blotting was performed to detect the relationship between SOCS1 and miR-155. Results: Luteolin inhibited RSV replication, as shown by the decreased viral titer and RSV-F mRNA expression both in vitro and in vivo. The antiviral activity of luteolin was attributed to the enhanced phosphorylation of STAT1, resulting in the increased production of ISGs. Further study showed that SOCS1 was downregulated by luteolin and SOCS1 is a direct target of microRNA-155 (miR-155). Inhibition of miR-155 rescued luteolin-mediated SOCS1 downregulation, whereas upregulation of miR-155 enhanced the inhibitory effect of luteolin. Conclusion: Luteolin inhibits RSV replication by regulating the miR-155/SOCS1/STAT1 signaling pathway.

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24 Interferon-independent, STAT1-mediated Inhibition of Respiratory Syncytial Virus Replication

Cytokine ◽

10.1016/j.cyto.2007.07.029 ◽

2007 ◽

Vol 39 (1) ◽

pp. 7

Author(s):

Troy D. Cline ◽

Sara E. Mertz ◽

Russell K. Durbin ◽

Joan E. Durbin

Keyword(s):

Respiratory Syncytial Virus ◽

Virus Replication ◽

Syncytial Virus

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siRNA-Mediated Simultaneous Regulation of the Cellular Innate Immune Response and Human Respiratory Syncytial Virus Replication

Biomolecules ◽

10.3390/biom9050165 ◽

2019 ◽

Vol 9 (5) ◽

pp. 165 ◽

Cited By ~ 4

Author(s):

María Martín-Vicente ◽

Salvador Resino ◽

Isidoro Martínez

Keyword(s):

Immune Response ◽

Respiratory Syncytial Virus ◽

Virus Replication ◽

Innate Immune Response ◽

Human Respiratory Syncytial Virus ◽

Innate Immune ◽

Viral Fusion ◽

Small Interfering Rnas ◽

Syncytial Virus ◽

Nucleoprotein N

Human respiratory syncytial virus (HRSV) infection is a common cause of severe lower respiratory tract diseases such as bronchiolitis and pneumonia. Both virus replication and the associated inflammatory immune response are believed to be behind these pathologies. So far, no vaccine or effective treatment is available for this viral infection. With the aim of finding new strategies to counteract HRSV replication and modulate the immune response, specific small interfering RNAs (siRNAs) were generated targeting the mRNA coding for the viral fusion (F) protein or nucleoprotein (N), or for two proteins involved in intracellular immune signaling, which are named tripartite motif-containing protein 25 (TRIM25) and retinoic acid-inducible gene-I (RIG-I). Furthermore, two additional bispecific siRNAs were designed that silenced F and TRIM25 (TRIM25/HRSV-F) or N and RIG-I (RIG-I/HRSV-N) simultaneously. All siRNAs targeting N or F, but not those silencing TRIM25 or RIG-I alone, significantly reduced viral titers. However, while siRNAs targeting F inhibited only the expression of the F mRNA and protein, the siRNAs targeting N led to a general inhibition of viral mRNA and protein expression. The N-targeting siRNAs also induced a drastic decrease in the expression of genes of the innate immune response. These results show that both virus replication and the early innate immune response can be regulated by targeting distinct viral products with siRNAs, which may be related to the different role of each protein in the life cycle of the virus.

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Generation of Bovine Respiratory Syncytial Virus (BRSV) from cDNA: BRSV NS2 Is Not Essential for Virus Replication in Tissue Culture, and the Human RSV Leader Region Acts as a Functional BRSV Genome Promoter

Journal of Virology ◽

10.1128/jvi.73.1.251-259.1999 ◽

1999 ◽

Vol 73 (1) ◽

pp. 251-259 ◽

Cited By ~ 634

Author(s):

Ursula J. Buchholz ◽

Stefan Finke ◽

Karl-Klaus Conzelmann

Keyword(s):

Cell Culture ◽

Respiratory Syncytial Virus ◽

Rna Polymerase ◽

Virus Replication ◽

Nonstructural Protein ◽

Bovine Respiratory Syncytial Virus ◽

T7 Rna Polymerase ◽

Leader Region ◽

Successful Recovery ◽

Syncytial Virus

ABSTRACT In order to generate recombinant bovine respiratory syncytial virus (BRSV), the genome of BRSV strain A51908, variant ATue51908, was cloned as cDNA. We provide here the sequence of the BRSV genome ends and of the entire L gene. This completes the sequence of the BRSV genome, which comprises a total of 15,140 nucleotides. To establish a vaccinia virus-free recovery system, a BHK-derived cell line stably expressing T7 RNA polymerase was generated (BSR T7/5). Recombinant BRSV was reproducibly recovered from cDNA constructs after T7 RNA polymerase-driven expression of antigenome sense RNA and of BRSV N, P, M2, and L proteins from transfected plasmids. Chimeric viruses in which the BRSV leader region was replaced by the human respiratory syncytial virus (HRSV) leader region replicated in cell culture as efficiently as their nonchimeric counterparts, demonstrating that allcis-acting sequences of the HRSV promoter are faithfully recognized by the BRSV polymerase complex. In addition, we report the successful recovery of a BRSV mutant lacking the complete NS2 gene, which encodes a nonstructural protein of unknown function. The NS2-deficient BRSV replicated autonomously and could be passaged, demonstrating that NS2 is not essential for virus replication in cell culture. However, growth of the mutant was considerably slower than and final infectious titers were reduced by a factor of at least 10 compared to wild-type BRSV, indicating that NS2 provides a supporting factor required for full replication capacity.

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TRIM22 inhibits respiratory syncytial virus replication by targeting JAK‐STAT1/2 signaling

Journal of Medical Virology ◽

10.1002/jmv.26436 ◽

2020 ◽

Author(s):

Yishu Wang ◽

Yiling Chen ◽

Ying Lin ◽

Yingqin Quan ◽

Xiaoping Xiao ◽

...

Keyword(s):

Respiratory Syncytial Virus ◽

Virus Replication ◽

Syncytial Virus

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Contribution of the Respiratory Syncytial Virus G Glycoprotein and Its Secreted and Membrane-Bound Forms to Virus Replication in Vitro and in Vivo

Virology ◽

10.1006/viro.2001.1138 ◽

2001 ◽

Vol 289 (2) ◽

pp. 283-296 ◽

Cited By ~ 160

Author(s):

Michael N. Teng ◽

Stephen S. Whitehead ◽

Peter L. Collins

Keyword(s):

Respiratory Syncytial Virus ◽

Virus Replication ◽

Membrane Bound ◽

Syncytial Virus

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Induction of type I interferons and interferon-inducible Mx genes during respiratory syncytial virus infection and reinfection in cotton rats

Journal of General Virology ◽

10.1099/vir.0.83294-0 ◽

2008 ◽

Vol 89 (1) ◽

pp. 261-270 ◽

Cited By ~ 30

Author(s):

Lioubov M. Pletneva ◽

Otto Haller ◽

David D. Porter ◽

Gregory A. Prince ◽

Jorge C. G. Blanco

Keyword(s):

Gene Expression ◽

Respiratory Syncytial Virus ◽

Virus Replication ◽

Surrogate Marker ◽

Type I Interferons ◽

Type I ◽

Dependent Manner ◽

Type I Ifn ◽

Syncytial Virus

Respiratory syncytial virus (RSV) is the primary cause of bronchiolitis in young children. In general, RSV is considered to be a poor inducer of type I (alpha/beta) interferons (IFNs). Measurement of active type I IFN production during infection in vivo is demanding, as multiple IFN subtypes with overlapping activities are produced. In contrast, Mx gene expression, which is tightly regulated by type I IFN expression, is easily determined. This study therefore measured Mx expression as a reliable surrogate marker of type I IFN activity during RSV infection in vivo in a cotton rat model. It was shown that expression of Mx genes was dramatically augmented in the lungs of infected animals in a dose- and virus strain-dependent manner. The expression of Mx genes in the lungs was paralleled by their induction in the nose and spleen, although in spleen no simultaneous virus gene expression was detected. Reinfection of RSV-immune animals leads to abortive virus replication in the lungs. Thus, type I IFN and Mx gene expression was triggered in reinfected animals, even though virus could not be isolated from their lungs. Furthermore, it was demonstrated that immunity to RSV wanes with time. Virus replication and Mx gene expression became more prominent with increasing intervals between primary infection and reinfection. These results highlight the role of type I IFN in modulation of the immune response to RSV.

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