The cysteine-rich region of respiratory syncytial virus attachment protein inhibits innate immunity elicited by the virus and endotoxin

Polack, Fernando P.; Irusta, Pablo M.; Hoffman, Scott J.; Schiatti, M. Paula; Melendi, Guillermina A.; Delgado, María Florencia; Laham, Federico R.; Thumar, Bhagvanji; Hendry, R. Michael; Melero, José A.; Karron, Ruth A.; Collins, Peter L.; Kleeberger, Steven R.

doi:10.1073/pnas.0409478102

Cited by 101 publications

(108 citation statements)

References 32 publications

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“…Support for this suggestion comes from the observations that susceptibility to severe HRSV infection in infants is linked to polymorphisms in SP-A and SP-D genes [76,88] and SP-A deficient mice have more severe HRSV infection than their wild-type littermates [85]. Furthermore, there is evidence that the HRSV G protein can suppress TLR4-mediated cytokine production by monocytes and macrophages by inhibiting nuclear translocation of NF-κB [104] ( Fig. 3).…”

Section: The Role Of the G Protein In The Pathogenesis Of Brsvmentioning

confidence: 93%

Bovine respiratory syncytial virus infection

Valarcher¹,

2007

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-Bovine respiratory syncytial virus (BRSV) belongs to the pneumovirus genus within the family Paramyxoviridae and is a major cause of respiratory disease in young calves. BRSV is enveloped and contains a negative sense, single-stranded RNA genome encoding 11 proteins. The virus replicates predominantly in ciliated respiratory epithelial cells but also in type II pneumocytes. It appears to cause little or no cytopathology in ciliated epithelial cell cultures in vitro, suggesting that much of the pathology is due to the host's response to virus infection. RSV infection induces an array of pro-inflammatory chemokines and cytokines that recruit neutrophils, macrophages and lymphocytes to the respiratory tract resulting in respiratory disease. Although the mechanisms responsible for induction of these chemokines and cytokines are unclear, studies on the closely related human (H)RSV suggest that activation of NF-κB via TLR4 and TLR3 signalling pathways is involved. An understanding of the mechanisms by which BRSV is able to establish infection and induce an inflammatory response has been facilitated by advances in reverse genetics, which have enabled manipulation of the virus genome. These studies have demonstrated an important role for the non-structural proteins in anti-interferon activity, a role for a virokinin, released during proteolytic cleavage of the fusion protein, in the inflammatory response and a role for the SH and the secreted form of the G protein in establishing pulmonary infection. Knowledge gained from these studies has also provided the opportunity to develop safe, stable, live attenuated virus vaccine candidates.

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Section: The Role Of the G Protein In The Pathogenesis Of Brsvmentioning

confidence: 93%

Bovine respiratory syncytial virus infection

Valarcher¹,

2007

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“…Known suppressors of innate immunity are the RSV G protein or non-structural (NS) proteins of influenza, RSV and other respiratory viruses (Arnold et al, 2004;Liu et al, 2016;Polack et al, 2005;Zheng et al, 2015). In vitro, the RSV G protein suppresses the inflammatory response of several cell types to components of the virus itself, but also dampens monocytic release of IL-6 and IL-1b upon stimulation with endotoxin.…”

Section: Other Mechanismsmentioning

confidence: 99%

Viral–bacterial interactions in the respiratory tract

Bellinghausen

Rohde

Savelkoul

et al. 2016

Journal of General Virology

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“…Viral titer was done with right lung lobes following procedures described previously (23). Briefly, the right lung (n 5 3/group) was ground in HBSS, debris was pelleted by centrifugation, and samples were plated on Hep-2 cells.…”

Section: Lung Viral Titrationmentioning

confidence: 99%

Antiviral Activity of Nrf2 in a Murine Model of Respiratory Syncytial Virus Disease

Cho

Imani

Miller-DeGraff

et al. 2009

Am J Respir Crit Care Med

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175

170

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Rationale: Respiratory syncytial virus (RSV) is the most frequent cause of significant lower respiratory illness in infants and young children, but its pathogenesis is not fully understood. The transcription factor Nrf 2 protects lungs from oxidative injury and inflammation via antioxidant response element (ARE)-mediated gene induction. Objectives: The current study was designed to determine the role of Nrf 2-mediated cytoprotective mechanisms in murine airway RSV disease. Methods: Nrf 2-deficient (Nrf 2 2/2 ) and wild-type (Nrf 2 1/1 ) mice were intranasally instilled with RSV or vehicle. In a separate study, Nrf 2 1/1 and Nrf 2 2/2 mice were treated orally with sulforaphane (an Nrf 2-ARE inducer) or phosphate-buffered saline before RSV infection. Measurements and Main Results: RSV-induced bronchopulmonary inflammation, epithelial injury, and mucus cell metaplasia as well as nasal epithelial injury were significantly greater in Nrf 2 2/2 mice than in Nrf 2 1/1 mice. Compared with Nrf 2 1/1 mice, significantly attenuated viral clearance and IFN-g, body weight loss, heightened protein/ lipid oxidation, and AP-1/NF-kB activity along with suppressed antioxidant induction was found in Nrf 2 2/2 mice in response to RSV. Sulforaphane pretreatment significantly limited lung RSV replication and virus-induced inflammation in Nrf 2 1/1 but not in Nrf 2 2/2 mice. Conclusions: The results of this study support an association of oxidant stress with RSV pathogenesis and a key role for the Nrf 2-ARE pathway in host defense against RSV.

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The cysteine-rich region of respiratory syncytial virus attachment protein inhibits innate immunity elicited by the virus and endotoxin

Cited by 101 publications

References 32 publications

Bovine respiratory syncytial virus infection

Bovine respiratory syncytial virus infection

Viral–bacterial interactions in the respiratory tract

Antiviral Activity of Nrf2 in a Murine Model of Respiratory Syncytial Virus Disease

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