Na Zhou’s research while affiliated with Chongqing Medical University and other places

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Publications (10)


Knockdown of NS1 reduced airway inflammation in late-stage RSV infection in mice. RSV-infected mice, mock mice treated with siCON or siNS1 were assessed for airway inflammation. BALF was collected for inflammatory cell counts. A Inflammatory cell number, including total cells, macrophages(Macro), lymphocytes(Lympho), neutrophils(Neutro), and eosinophils(Eosino), in the BALF on day 21 after NS1 knockdown are shown (n = 6). B-C Lung tissue histology was performed on day 21 after RSV infection (a: siCON group; b: siNS1 group; c: RSV + siCON; d: RSV + siNS1. C Lung injury scores) (n = 3). D Expression levels of HMGB1 and H1.0 in lungs. E–F HMGB1 and H1.0 protein level quantification (n = 3). ** and *** represent P < 0.001 and P < 0.0001, respectively(RSV + siCON or RSV + siNS1 group compared with control siCON group); ^ and ^^ represent P < 0.05 and P < 0.001 respectively(RSV + siNS1 compared with RSV + siCON group)
RSV infection increased expression and release of HMGB1 in A549 cells. RSV-infected cells were collected 0, 12, 24, and 36 h after RSV infection. Total protein was extracted for protein expression level assessment. Supernatants were collected at 24 h for HMGB1 detection. HMGB1 (A) and NS1 (C) protein levels in A549 cells 0, 12, 24, and 36 h after RSV infection (n = 3). B, D Quantification of HMGB1 and NS1 protein levels (n = 3). E HMGB1 protein levels in cytoplasm and nucleus 24 h after RSV infection. F-G Quantification of HMGB1 protein levels in cytoplasm and nucleus (n = 3). H HMGB1 levels in supernatants were measured by ELISA (n = 6). *, **, *** represent P < 0.05, P < 0.01, and P < 0.001 respectively(compared with Mock (or 0 h) group). ^^^ represents P < 0.001(compared with 24 h group). The Kruskal–Wallis test was employed to compare RSV with the mock group
Knockdown of NS1 reduced HMGB1 and H1.0 expression and release in A549 cells. A549 cells were infected with RSV for 6 h, after which siCON and siNS1 were transinfected for another 24 h. A HMGB1 protein levels after NS1 knockdown. B Quantification of HMGB1 protein levels (n = 3). C HMGB1 expression levels within the cytoplasm and nucleus were determined using a fluorescence microscope. D Mean fluorescence was determined by Image-Pro Plus (n = 3). E HMGB1 levels in the supernatants, with means ± standard deviation (SD) shown for six independent experiments (n = 6). F H1.0 protein levels 24 and 36 h after RSV infection. G Quantification of H1.0 protein levels (n = 3). H-I Quantification of H1.0 protein levels after NS1 knockdown (n = 3). * and ** represent P < 0.05 and P < 0.01, respectively(siNS1 compared with siCON group or compared with 0 h in panel G). ^ RSV + siNS1 group compared with RSV + siCON (P < 0.05). The Kruskal–Wallis test was employed to compare siNS1 with the siCON group
Knockdown of NS1 reduced HMGB1 and H1.0 expression in 16HBE cells. RSV-infected 16HBE cells were collected 0, 24, and 36 h after RSV infection. Total protein was extracted for protein expression level assessment. For siNS1 knockdown, 16HBE cells were infected with RSV for 6 h, then siCON or siNS1 was transinfected for another 24 h. A HMGB1 and H1.0 protein levels in 16HBE cells 0, 24, and 36 h after RSV infection (n = 3). B-C Quantification of HMGB1 and H1.0 protein levels (n = 3). D HMGB1 and H1.0 protein levels after NS1 knockdown. E–F Quantification of HMGB1 and H1.0 protein levels (n = 3). * represent P < 0.05(compared with 0 h represent); ** represent P < 0.01(compared with siCON group). The Kruskal–Wallis test was employed to compare siNS1 with the siCON group
Overexpression of NS1 increased HMGB1 expression in A549 cells. A549 cells were treated with NS1 or control lentivirus for 72 h, then collected for protein detection or immunofluorescence analysis. A-C HMGB1 and H1.0 protein levels after overexpression of NS1 (A, the GFP inbdicated lentivirus transfection) and quantification of HMGB1 (B) and H1.0 (C) protein levels (n = 3). D HMGB1 expression within the cytoplasm and nucleus determined by fluorescence microscope. E Mean fluorescence of HMGB1 determined by Image-Pro Plus (n = 3). F H1.0 expression within the nucleus determined by fluorescence microscope. G Mean fluorescence of H1.0 determined by Image-Pro Plus (n = 3). * represent P < 0.05(siNS1 compared with siCON group).The Kruskal–Wallis test was employed to compare LV-NS1 with the LV-CON group

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Nonstructural Protein 1 Mediates HMGB1 Release by Targeting Histone H1.0 After Respiratory Syncytial Virus Infection In Vivo and In Vitro
  • Article
  • Full-text available

May 2025

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2 Reads

Inflammation

Na Zhou

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Siyi Che

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Hui Zhai

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[...]

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Jun Xie

High mobility group box-1 (HMGB1) is implicated in airway inflammation during the late phase of respiratory syncytial virus (RSV) infection. Despite its recognized role, the specific mechanism underlying its release post-RSV infection remains ambiguous. The nonstructural protein 1 (NS1) has been associated with interactions with numerous host proteins, affecting diverse physiological processes, and it is speculated to be involved in the release of HMGB1. We utilized an in vivo model of RSV-infected mice and an in vitro model of RSV-infected A549 and 16HBE cells to investigate the role of NS1 in promoting HMGB1 release. Small interfering RNA was employed to deplete NS1, while lentiviral vectors were used for NS1 overexpression. The interaction between NS1 and H1.0 was confirmed by immunofluorescence analysis, immunoprecipitation, GST pull-down assays, surface plasmon resonance analysis and in silico study. Our study revealed that silencing the NS1 gene reduced the levels of HMGB1 protein and suppressed airway inflammation during the late stage of RSV infection. Depletion of NS1 led to decreased levels of intracellular and extracellular HMGB1 in A549 and 16HBE cells, while over-expression of NS1 increased HMGB1 expression. Furthermore, NS1 and HMGB1 directly interacted with histone H1.0, as confirmed by GST pull-down, surface plasmon resonance and in silico analyses. Overexpression of NS1 disrupted the binding of HMGB1 to H1.0, while silencing of NS1 enhanced their interaction. The research findings indicate that NS1 interacts with H1.0, thereby inhibiting the binding of HMGB1 to H1.0. Consequently, this interaction results in the release of HMGB1 into both the cytoplasm and the extracellular space.

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Andrographolide exerts anti-respiratory syncytial virus activity by up-regulating heme oxygenase-1 independent of interferon responses in human airway epithelial cells

March 2023

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58 Reads

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6 Citations

Molecular Biology Reports

Background Respiratory syncytial virus (RSV) is the leading cause of mortality and morbidity in children under the age of five. Despite this, there is still a lack of safe and effective vaccines and antiviral agents for clinical use. Andrographolide exerts antiviral functions against a variety of viruses, but whether (and how) it exerts antiviral effects on RSV remains unclear. Methods and results In vitro RSV infection models using A549 and 16HBE cell lines were established, and the effects of andrographolide on RSV were analyzed via RSV N gene load and proinflammatory cytokine levels. The RNA transcriptome was sequenced, and data were analyzed by R software. Andrographolide-related target genes were extracted via network pharmacology using online databases. Lentiviral transfection was applied to knockdown the heme oxygenase-1 gene (Hmox1, HO-1). Results showed that andrographolide suppressed RSV replication and attenuated subsequent inflammation. Network pharmacology and RNA sequencing analysis indicated that the hub gene HO-1 may play a pivotal role in the anti-RSV effects of andrographolide. Furthermore, andrographolide exerted antiviral effects against RSV partially by inducing HO-1 but did not activate the antiviral interferon response. Conclusion Our findings demonstrated that andrographolide exerted anti-RSV activity by up-regulating HO-1 expression in human airway epithelial cells, providing novel insights into potential therapeutic targets and drug repurposing in RSV infection.


Figure 4 Effects of intranasal Andro-S on TLR1-9 mRNA expression in the lungs of immunocompromised BALB/c mice five days after RSV infection. Relative mRNA levels of TLR1 (A), TLR2 (B), TLR3 (C), TLR4 (D), TLR5 (E), TLR6 (F), TLR7 (G), TLR8 (H), and TLR9 (I) in lung tissues as determined by qRT-PCR. n≥4. *, P<0.05; **, P<0.01; ***, P<0.001 vs. PBS + saline. TLR, Toll-like receptor; RSV, respiratory syncytial virus; PBS, phosphate-buffered saline; Andro-S, andrographolide sulfonate; qRT-PCR, quantitative real-time polymerase chain reaction.
Andrographolide sulfonate downregulation of TLR3-TRIF and amelioration of airway inflammation caused by respiratory syncytial virus infection

January 2023

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7 Reads

Journal of Thoracic Disease

Background Andrographolide sulfonate (Andro-S), a traditional Chinese medicine, is commonly used to treat pediatric respiratory tract infections in China. However, its therapeutic effects in infections caused by respiratory syncytial virus (RSV) have not been reported. We thus aimed to investigate the therapeutic effects of Andro-S using a mouse model of RSV infection-induced airway inflammation. Methods Immunocompromised (cyclophosphamide-treated) BALB/c mice were intranasally infected with RSV and treated with intranasal or intraperitoneal Andro-S once daily for five consecutive days, starting on the day of infection. Histopathological changes in the lung were evaluated using hematoxylin and eosin staining. Total inflammatory cell counts and macrophage, lymphocyte, neutrophil, and eosinophil counts in the bronchoalveolar lavage fluid (BALF) were microscopically determined. Interferon-γ (IFN-γ) levels in the BALF were detected using enzyme-linked immunosorbent assay (ELISA). The messenger RNA levels of RSV nucleoprotein (N) and Toll-like receptors (TLRs) 1–9 in lung tissues were determined with quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of RSV N, RSV fusion protein (F), TLR2, TLR3, and TIR domain-containing adapter-inducing interferon-β (TRIF) were detected via Western blot analysis. Results RSV infection caused lung inflammation, manifesting as bronchiolitis, alveolitis, and perivascular inflammation; increased the number of inflammatory cells; and elevated IFN-γ levels in the BALF. Lung inflammation was positively correlated with pulmonary RSV N levels in infected mice. Intranasal Andro-S significantly downregulated RSV N, RSV F, TLR3, and TRIF protein expression in the lung and ameliorated lung inflammation in infected animals. However, intraperitoneal Andro-S showed no effects on lung inflammation caused by RSV infection. Conclusions Intranasal Andro-S inhibits RSV replication and ameliorates RSV infection-induced lung inflammation by downregulating TLR3 and TRIF. Therefore, intranasal administration may be a suitable drug delivery method for treating RSV infection.


Andrographolide exerts anti-respiratory syncytial virus activity by up-regulating heme oxygenase-1 independent of interferon responses in human airway epithelial cells

August 2022

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40 Reads

Background: Respiratory syncytial virus (RSV), the leading cause of mortality and morbidity in children under the age of five, is still lacking in safe and effective vaccines and antiviral agents for clinical use. Andrographolide exerts antiviral functions against a variety of viruses, but whether (and how) it exerts antiviral effects on RSV remains unclear. Methods and results: In vitro RSV infection models using A549 and 16HBE cell lines were established, and the effect of andrographolide on RSV was analyzed via RSV N gene load and proinflammatory levels. The RNA transcriptome was sequenced and data were analyzed by R software. Lentivirus was transfected to knockdown the expression of HO-1. Results showed andrographolide suppressed RSV replication and attenuated subsequent inflammation. RNA sequencing indicated that the hub gene heme oxygenase-1 (HO-1) may play a pivotal role in the anti-RSV effects of andrographolide. Furthermore, results verified that andrographolide exert antiviral effects against RSV partially by inducing HO-1, but did not activate the antiviral interferon response. Conclusion: Our findings demonstrated that andrographolide exerted anti-RSV activity by up-regulating HO-1 in human airway epithelial cells, which may provide novel insights into potential therapeutic targets and drug repurposing in RSV infection.


An Interaction of LPS and RSV Infection in Augmenting the AHR and Airway Inflammation in Mice

October 2017

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43 Reads

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8 Citations

Inflammation

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infection (LRTI) in children under 5 years of age, especially infants with severe bronchiolitis. Our preliminary clinical experiments showed that bacterial colonization was commonly observed in children with virus-induced wheezing, particularly in those with recurrent wheezing, suggesting that bacterial colonization with an accompanying viral infection may contribute to disease severity. In most cases, RSV-infected infants were colonized with pathogenic bacteria (mainly Gram-negative bacteria). LPS is the main component of Gram-negative bacteria and acts as a ligand for Toll-like receptor 4 (TLR4). Relevant studies have reported that the TLR family is crucial in mediating the link between viral components and immunologic responses to infection. Of note, TLR4 activation has been associated with disease severity during RSV infection. In the present study, we identified that LPS aggravated RSV-induced AHR and airway inflammation in BALB/c mice using an RSV coinfection model. We found that the airway inflammatory cells and cytokines present in BALF and TRIF in lung tissue play a role in inducing AHR and airway inflammation upon RSV and bacteria coinfection, which might occur through the TRIF-MMP-9-neutrophil-MMP-9 signalling pathway. These results may aid in the development of novel treatments and improve vaccine design.


The NS1 protein of Respiratory syncytial virus blocks glucocorticoid receptor nuclear translocation by targeting IPO13 may account for glucocorticoid insensitive

September 2017

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40 Reads

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16 Citations

The Journal of Infectious Diseases

In spite of their powerful anti-inflammatory effect, glucocorticoids have shown no significant clinical benefit in respiratory syncytial virus (RSV)-induced bronchiolitis, the reason for which remains unclear. Upon glucocorticoid binding, the cytoplasmic glucocorticoid receptor (GR) translocates to the nucleus with the help of importin-13 (IPO13). Here, we report that RSV infection reduced GR nuclear translocation in the nasopharyngeal aspirate (NPA) of the RSV-infected infants, lungs of infected mice, and A549 cells, which coincided with decreased IPO13 expression. This led to repression of GR-induced anti-inflammatory genes, such that dexamethasone failed to suppress airway inflammation and AHR in the infected mice. The anti-GR effect of RSV was mediated by viral nonstructural protein, NS1, which likely functioned by competing with IPO13 for GR-binding. Our findings provide a mechanism for the ineffectiveness of glucocorticoids in RSV-related disease and highlight the potential to target the IPO13-GR axis as a treatment for multiple glucocorticoid-related diseases.


Downregulation of NGF attenuates AHR persistence induced by respiratory syncytial virus infection in BALB/c mice (870.3)

April 2014

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10 Reads

RSV infection causes acute morbidity and recurrent wheezing that could persist up to several years, but the relevant mechanisms remain unclear. Because NGF is involved in developing AHR during acute phase of RSV infection, we asked whether RSV infection also induced a chronic AHR in mice, and if so, what role pulmonary NGF played. Mice at day 7, 14, 21, 30 and 60 after intranasal inoculation of RSV were either placed in a whole body plethysmograph to measure their Penh responses to increasing doses of aerosol methacholine or euthanized for collecting BALF to detect pulmonary NGF. We found that AHR and NGF/BDNF were gradually increased and persisted 60 days after RSV infection. To define whether NGF was responsible for the AHR persistence via TLRs‐TRIF signaling pathway, the AHR was tested in other mice after administration of anti‐NGF neutralized antibody (ip) once on day 14 postinfection and resveratrol (inhibitor of TRIF, ip) daily from day 0 to day 21 postinfection, respectively. The RSV‐induced AHR and NGF were markedly attenuated by both treatments. Additionally, RSV infection also produced chronic airway inflammation 60 days postinfection that was diminished by resveratrol but not by anti‐NGF. We conclude that NGF is involved in generating the RSV‐induced AHR probably via activation of TLRs‐TRIF signaling pathway, while the latter but not NGF participates the RSV‐induced chronic airway inflammation.


Respiratory syncytial virus‐induced chronic airway inflammation and AHR (CAI‐CAHR) is associated with upregulation of Th2‐like cytokines via TLRs‐TRIF but not TSLP signaling pathway (870.2)

April 2014

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6 Reads

We have shown that TLRs‐TRIF pathway is responsible for the RSV infection‐induced CAI‐CAHR. This pathway is reportedly involved in Th2 responses that are predominate in the patients with severe RSV infection. Thus, we hypothesized that the RSV‐induced CAI‐CAHR was associated with upregulation of Th2‐like cytokines dependent on TLRs‐TRIF pathway. Mice at day 7, 14, 21, 30 and 60 postinfection were placed in a whole body plethysmograph to define AHR or euthanized to determine Th2‐like cytokines (in BALF) and airway inflammation (inflammatory cells in BALF and histopathology). RSV infection induced CAI‐CAHR concomitant with significant (All P < 0.05 or 0.01) elevation of IL‐4, IL‐5, IL‐10, IL‐13, TNF‐α and TSLP from day 14 to 60 postinfection with the peak at day 21. The same protocols were performed in other mice after giving resveratrol (inhibitor of TRIF, ip) daily from day 0 to day 21 postinfection. Resveratrol treatment strikingly reduced the RSV infection‐induced Th2‐like cytokines and CAI‐CAHR. As Th2‐like cytokines are also controlled by TSLP in asthmatic patients and animals, anti‐TSLP neutralized antibody (ip, on day 14 after postinfection) was utilized in the subsequent study. This treatment failed to alter the peak Th2‐like cytokines and CAI‐CAHR. Our results suggest that RSV infection‐induced CAI‐CAHR is associated with upregulation of Th2‐like cytokines via TLRs‐TRIF but not TSLP signaling pathway.


FIG 1 RSV reduced SARM expression in vivo and in vitro . (A) Cells were infected with RSV at an MOI of 10. (A1) SARM and TRIF protein levels were detected by immunoblotting at the time points indicated. (A2) RSV reduced the SARM/ ␤ -actin ratio compared to the control group. *, P Ͻ 0.05 48 h and 72 h after RSV infection versus the control. (A3) RSV infection increased the TRIF/ ␤ -actin ratio compared to that of the control group. **, P Ͻ 0.01 48 h after RSV infection versus the control. *, P Ͻ 0.05 72 h after RSV infection versus the control. (B) BALB/c mice were infected by live RSV at 4.5 ϫ 10 7 PFU. The lungs of the infected 
FIG 2 SARM siRNA 3-1-GFP or SARM siRNA-negative-control-GFP organization and protein expression. (A) The SARM siRNA-GFP signal in freshly harvested lungs demonstrates polymer formation by the SARM siRNA transgene, i.e., GFP in lungs of transgenic mice, compared to the wild-type control. Images show cross-sections of mouse lung proximal and distal airway sections from transgenic mice or wild-type control mice stained with DAPI as a nuclear stain. Corresponding differential interference contrast/DAPI images are shown. Wild-type images are shown as a control. (B1) Western blotting was used to evaluate the SARM and TRIF expression in wild-type control mice, RSV-infected mice, and RSV-infected mice treated with resveratrol (RES) (lanes 1 to 3). RSV-infected mice treated with RES were either transfected with SARM siRNA negative control (lane 4) or SARM siRNA 3-1 (lane 5). (B2) SARM siRNA reduced the SARM/ ␤ -actin ratio in the lungs of RES-treated mice. **, P Ͻ 0.01 for RES-treated, SARM siRNA 3-1-transfected mice versus RES-treated, siRNA negative- control-transfected mice. (B3) SARM siRNA increased the TRIF/ ␤ -actin ratio in the lungs of RES-treated mice. **, P Ͻ 0.01 for RES-treated, SARM siRNA 3-1-transfected mice versus RES-treated, siRNA negative-control-transfected mice. These experiments were performed three times with three mice per group. 
FIG 3 SARM knockdown increased inflammation in RSV-infected lungs. (A1) Histological examination of lung tissues was performed 5 days postresveratrol treatment. The lung tissues were fixed and stained with H&E (magnification, ϫ 100). (A2) Lung tissue inflammatory cell infiltration scores. ***, P Ͻ 0.001 for resveratrol (RES)-treated SARM siRNA 3-1-transfected mice versus RES-treated siRNA negative-control-transfected mice. (B) Cells were isolated by cytospin and stained with DiffQuik. Cells were counted using a hemocytometer. Values are expressed as the means; error bars are standard deviations (SD) ( n ϭ 3/group). Total numbers of cells were present in the BALF of the respective treatment groups. ***, P Ͻ 0.001 for RSV-infected versus RES-treated mice and RES-treated SARM siRNA 3-1-transfected mice versus RES-treated siRNA negative-control-transfected mice. Differences were found for lymphocytes between treatment groups. **, P Ͻ 0.01 for untreated versus RES-treated RSV-infected mice and untreated SARM siRNA 3-1-transfected mice versus RES-treated siRNA negative- control-transfected mice. (C) AHR was measured 5 days postresveratrol treatment and 1 day post-siRNA transfection in mice treated with increasing methacholine concentrations (3.125 to 50.0 mg/ml) by plethlysmography. Values are expressed as means Ϯ SD ( n ϭ 5/group). ***, P Ͻ 0.001 for RES- and SARM siRNA 3-1-treated mice versus RES- and siRNA negative-control-transfected mice. **, P Ͻ 0.01 for untreated mice versus RES-treated mice infected with RSV. (D) IFN- ␥ was measured by ELISA from BALF harvested 5 days post-RSV infection ( n ϭ 8/group). IFN- ␥ levels in BALF are shown. Values are expressed as means Ϯ SD ( n ϭ 8/group). *, P Ͻ 0.05 for untreated mice versus RES-treated mice. ***, P Ͻ 0.001 for RES-treated SARM siRNA 3-1-transfected mice versus RES-treated siRNA negative-control-transfected mice. (E) Viral titer was measured by qPCR. RSV-infected lungs were harvested 5 days post-RES treatment and 1 day post-SARM siRNA transfection. Values are expressed as means Ϯ SD ( n ϭ 5/group). There was no significant difference between untreated mice and RES-treated SARM siRNA 3-1-transfected mice. 
Resveratrol Inhibits the TRIF-Dependent Pathway by Upregulating Sterile Alpha and Armadillo Motif Protein, Contributing to Anti-Inflammatory Effects after Respiratory Syncytial Virus Infection

March 2014

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302 Reads

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67 Citations

Unlabelled: Respiratory syncytial virus (RSV) is the most important cause of lower respiratory tract infection in young children and the leading cause of infant hospitalization worldwide. Uncontrolled response to RSV is mediated by a toll-like receptor (TLR)-mediated immune response. Resveratrol possesses anti-RSV activity and is an inhibitor of the TRIF/TBK1/IRF-3 complex. We hypothesize that resveratrol inhibits the TRIF-dependent pathway through upregulation of SARM post-RSV infection. BALB/c mice were infected with RSV and were injected with resveratrol 1 h postinoculation. SARM short interfering RNA was administered to RSV-infected and resveratrol-treated mice. Lung function was measured by whole-body plethysmography, lung histopathology was examined, and lymphocytes in bronchoalveolar lavage fluid were quantified. SARM and TRIF protein expression were detected in the lung by Western blot analyses. The expression of gamma interferon in bronchoalveolar lavage fluid (BALF) was evaluated by enzyme-linked immunosorbent assay (ELISA). SARM expression was reduced and TRIF expression was increased after infection with RSV. Resveratrol increased SARM expression and decreased TRIF expression after RSV infection. SARM knockdown in resveratrol-treated mice enhanced gamma interferon production, RSV-induced airway inflammation, and airway hyperresponsiveness (AHR). Resveratrol decreased TRIF expression and prevented the RSV-mediated reduction of SARM expression. Resveratrol-mediated inhibition of the TRIF-dependent pathway may be dependent on SARM expression. Importance: Our study provides insights into the regulation of innate immunity in response to RSV infection. The results suggest that resveratrol-mediated alterations in SARM have therapeutic potential against RSV immunopathology caused by deregulation of the TLR-mediated immune response. Ultimately, improved insight into the complex interplay between TLR adaptor proteins and the occurrence of severe RSV infection might lead to novel therapeutic treatment strategies, such as TLR adjuvants.

Citations (5)


... As TLR2 is expressed on the apical surfaces of both tissues, TLR2 blockades may be useful for reducing hyperinflammation caused by Gram-positive pathogens when combined with appropriate antibiotics to adequately manage infection. TLR2 blockade, mediated by the p53 protein, may also reduce inflammatory responses to respiratory syncytial virus [178]. These therapies must be employed with caution; they may negatively affect immune homeostasis, as commensal organisms within the small intestine are known to maintain tolerance via TLR2 signaling [179]. ...

Reference:

Mucosal Immunity: Lessons from the Lower Respiratory and Small Intestinal Epithelia
p53 suppresses the inflammatory response following respiratory syncytial virus infection by inhibiting TLR2
  • Citing Article
  • February 2024

Virology

... Similarly, in the human hepatoma cell line infected by the hepatitis C virus (HCV), andrographolide induces an antiviral response via heme oxygenase-1 (HO-1) induction, increasing IFNα expression and the inhibition of HCV NS3/4A protease activity [74]. Similarly, andrographolide suppresses RSV replication via HO-1 induction in human airway epithelial cells but does not activate the antiviral IFN response [75]. On the other hand, andrographolide has been described to inhibit influenza virus replication; it may do so in a direct manner by binding to HA and NA to prevent the virus from entering or leaving the host cell; it also decreases inflammation by suppressing pro-inflammatory cytokines and chemokines via inhibiting the NF-κB signaling pathway, and even downregulating the Janus kinase/signal transducer and transcription (JAK/STAT) activation signals [49]. ...

Andrographolide exerts anti-respiratory syncytial virus activity by up-regulating heme oxygenase-1 independent of interferon responses in human airway epithelial cells

Molecular Biology Reports

... NS1 interacts with various host proteins, including Mediator subunits and RNApol II, influencing multiple physiological processes [5]. Our previous study revealed that NS1 competitively binds to the host transporter IPO13, impairing the nuclear translocation of the glucocorticoid receptor, resulting in reduced sensitivity to glucocorticoid therapy post RSV infection [6]. Therefore, further investigation is warranted to understand the significant role NS1 plays in the pathophysiological processes following RSV infection. ...

The NS1 protein of Respiratory syncytial virus blocks glucocorticoid receptor nuclear translocation by targeting IPO13 may account for glucocorticoid insensitive
  • Citing Article
  • September 2017

The Journal of Infectious Diseases

... Consequently, the level of TLR4 activation can serve as an indicator of disease severity in RSV infection. The interaction between RSV and LPS triggers AhR signaling and respiratory tract inflammation through the TRIF-MMP-9-neutrophil-MMP-9 signaling pathway (55). Consequently, inhibiting this co-infection interaction may prove beneficial in the development of vaccines and therapies for RSV infection in the future. ...

An Interaction of LPS and RSV Infection in Augmenting the AHR and Airway Inflammation in Mice

Inflammation

... However, in mice infected with RSV and treated with resveratrol, SARM1 became more expressed, whereas TRIF had reduced expression compared to untreated infected animals. The drug's effect was lost in animals treated with siRNA, reinforcing that resveratrol acts by reducing inflammation caused by RSV through the modulation of SARM1 expression (104). Resveratrol also proved to be a potent inhibitor of the signaling pathway originating from TRIF, further emphasizing the importance of SARM1 in regulating the mammalian immune response, as well as its potential as a therapeutic target for inflammatory diseases (105). ...

Resveratrol Inhibits the TRIF-Dependent Pathway by Upregulating Sterile Alpha and Armadillo Motif Protein, Contributing to Anti-Inflammatory Effects after Respiratory Syncytial Virus Infection