Human respiratory syncytial virus non-structural protein NS1 modifies miR-24 expression via transforming growth factor-β

Bakre, Abhijeet; Wu, Weining; Hiscox, Julian A.; Spann, Kirsten; Teng, Michael N.; Tripp, Ralph A.

doi:10.1099/jgv.0.000261

Cited by 24 publications

(27 citation statements)

References 109 publications

(164 reference statements)

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“…Viral proteins have also been reported to modulate miRNA expression. Bakre et al 8,. reported that respiratory syncytial virus (RSV) NS1 protein interacts with KLF6 transcription factor to modulate miR-24 expression which facilitates viral replication8.…”

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confidence: 97%

Japanese Encephalitis Virus exploits the microRNA-432 to regulate the expression of Suppressor of Cytokine Signaling (SOCS) 5

Sharma

Kumawat

Rastogi

et al. 2016

Sci Rep

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Japanese encephalitis virus (JEV) is a plus strand RNA virus, which infects brain. MicroRNAs are regulatory non-coding RNAs which regulate the expression of various genes in cells. Viruses modulate the expression of various microRNAs to suppress anti-viral signaling and evade the immune response. SOCS (Suppressor of cytokine signalling) family of proteins are negative regulators of anti-viral Jak-STAT pathway. In this study, we demonstrated the regulatory role of SOCS5 in Jak-STAT signaling and its exploitation by JEV through a microRNA mediated mechanism. JEV infection in human brain microglial cells (CHME3) downregulated the expression of miR-432, and upregulated SOCS5 levels. SOCS5 was validated as a target of miR-432 by using 3′UTR clone of SOCS5 in luciferase vector along with miR-432 mimic. The overexpression of miR-432 prior to JEV infection enhanced the phosphorylation of STAT1 resulting into increased ISRE activity and cellular inflammatory response resulting into diminished viral replication. The knockdown of SOCS5 resulted into increased STAT1 phosphorylation and suppressed viral replication. JEV infection mediated downregulation of miR-432 leads to SOCS5 upregulation, which helps the virus to evade cellular anti-viral response. This study demonstrated that JEV utilizes this microRNA mediated strategy to manipulate cellular immune response promoting JEV pathogenesis.

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mentioning

confidence: 97%

Japanese Encephalitis Virus exploits the microRNA-432 to regulate the expression of Suppressor of Cytokine Signaling (SOCS) 5

Sharma

Kumawat

Rastogi

et al. 2016

Sci Rep

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“…Previous studies with lung epithelial cells revealed a role of TGF-β in modulating RSV infection (McCann and Imani, 2007; Gibbs et al, 2009; Mgbemena et al, 2011; Bakre et al, 2015), since blocking TGF-β activity reduced RSV infection of lung epithelial cells (McCann and Imani, 2007; Gibbs et al, 2009; Mgbemena et al, 2011). In that context, the exact role of TGF-β during RSV infection is still unknown.…”

Section: Resultsmentioning

confidence: 96%

“…RSV infection results in TGF-β production from non-myeloid cells like lung epithelial cells (McCann and Imani, 2007; Gibbs et al, 2009; Mgbemena et al, 2011; Bakre et al, 2015). However, it is still unknown whether TGF-β is released from RSV infected myeloid cells like macrophages.…”

Section: Resultsmentioning

confidence: 99%

“…Although TGF-β is released from RSV infected epithelial cells (McCann and Imani, 2007; Gibbs et al, 2009; Mgbemena et al, 2011; Bakre et al, 2015), the mechanism triggering TGF-β production during infection is still unknown. Since RSV induces autophagy (Morris et al, 2011; Reed et al, 2013; Owczarczyk et al, 2015), we next examined a possible role of autophagy in positively regulating TGF-β production during RSV infection.…”

Section: Resultsmentioning

confidence: 99%

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Autophagy, TGF-β, and SMAD-2/3 Signaling Regulates Interferon-β Response in Respiratory Syncytial Virus Infected Macrophages

Pokharel

Shil

Bose

2016

Front. Cell. Infect. Microbiol.

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Human respiratory syncytial virus (RSV) is a lung tropic virus causing severe airway diseases including bronchiolitis and pneumonia among infants, children, and immuno-compromised individuals. RSV triggers transforming growth factor-β (TGF-β) production from lung epithelial cells and TGF-β facilitates RSV infection of these cells. However, it is still unknown whether RSV infected myeloid cells like macrophages produce TGF-β and the role of TGF-β if any during RSV infection of these cells. Our study revealed that RSV infected macrophages produce TGF-β and as a consequence these cells activate TGF-β dependent SMAD-2/3 signaling pathway. Further mechanistic studies illustrated a role of autophagy in triggering TGF-β production from RSV infected macrophages. In an effort to elucidate the role of TGF-β and SMAD-2/3 signaling during RSV infection, we surprisingly unfolded the requirement of TGF-β—SMAD2/3 signaling in conferring optimal innate immune antiviral response during RSV infection of macrophages. Type-I interferon (e.g., interferon-β or IFN-β) is a critical host factor regulating innate immune antiviral response during RSV infection. Our study revealed that loss of TGF-β—SMAD2/3 signaling pathway in RSV infected macrophages led to diminished expression and production of IFN-β. Inhibiting autophagy in RSV infected macrophages also resulted in reduced production of IFN-β. Thus, our studies have unfolded the requirement of autophagy—TGF-β—SMAD2/3 signaling network for optimal innate immune antiviral response during RSV infection of macrophages.

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“…Following the IFNAR1 mRNA interference by hRSV, the NS1 protein suppresses the expression of miR-24, by producing the Kruppel-like factor 6 (KLF6). Specifically, KLF6 induces the production of TGF-β, which in turn inhibits miR-24 and thought to cause cell arrest, reducing apoptosis and increasing viral replication (Bakre et al, 2015 ). This notion is supported by previous studies showing that NS1 and NS2 were involved in the inhibition of cell apoptosis in the early stages of the hRSV infection (Bitko et al, 2007 ).…”

Section: Effect Of Hrsv Proteins In the Innate Immune Response: Hrsv mentioning

confidence: 99%

Modulation of Host Immunity by Human Respiratory Syncytial Virus Virulence Factors: A Synergic Inhibition of Both Innate and Adaptive Immunity

Canedo-Marroquín

Acevedo-Acevedo

Rey-Jurado

et al. 2017

Front. Cell. Infect. Microbiol.

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The Human Respiratory Syncytial Virus (hRSV) is a major cause of acute lower respiratory tract infections (ARTIs) and high rates of hospitalizations in children and in the elderly worldwide. Symptoms of hRSV infection include bronchiolitis and pneumonia. The lung pathology observed during hRSV infection is due in part to an exacerbated host immune response, characterized by immune cell infiltration to the lungs. HRSV is an enveloped virus, a member of the Pneumoviridae family, with a non-segmented genome and negative polarity-single RNA that contains 10 genes encoding for 11 proteins. These include the Fusion protein (F), the Glycoprotein (G), and the Small Hydrophobic (SH) protein, which are located on the virus surface. In addition, the Nucleoprotein (N), Phosphoprotein (P) large polymerase protein (L) part of the RNA-dependent RNA polymerase complex, the M2-1 protein as a transcription elongation factor, the M2-2 protein as a regulator of viral transcription and (M) protein all of which locate inside the virion. Apart from the structural proteins, the hRSV genome encodes for the non-structural 1 and 2 proteins (NS1 and NS2). HRSV has developed different strategies to evade the host immunity by means of the function of some of these proteins that work as virulence factors to improve the infection in the lung tissue. Also, hRSV NS-1 and NS-2 proteins have been shown to inhibit the activation of the type I interferon response. Furthermore, the hRSV nucleoprotein has been shown to inhibit the immunological synapsis between the dendritic cells and T cells during infection, resulting in an inefficient T cell activation. Here, we discuss the hRSV virulence factors and the host immunological features raised during infection with this virus.

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Human respiratory syncytial virus non-structural protein NS1 modifies miR-24 expression via transforming growth factor-β

Cited by 24 publications

References 109 publications

Japanese Encephalitis Virus exploits the microRNA-432 to regulate the expression of Suppressor of Cytokine Signaling (SOCS) 5

Japanese Encephalitis Virus exploits the microRNA-432 to regulate the expression of Suppressor of Cytokine Signaling (SOCS) 5

Autophagy, TGF-β, and SMAD-2/3 Signaling Regulates Interferon-β Response in Respiratory Syncytial Virus Infected Macrophages

Modulation of Host Immunity by Human Respiratory Syncytial Virus Virulence Factors: A Synergic Inhibition of Both Innate and Adaptive Immunity

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