Comparative expression of Toll-like receptors and inflammatory cytokines in pigs infected with different virulent porcine reproductive and respiratory syndrome virus isolates

Zhang, Lili; Liu, Jie; Bai, Juan; Wang, Xiaoye; Li, Yufeng; Jiang, Ping

doi:10.1186/1743-422x-10-135

Cited by 37 publications

(22 citation statements)

References 34 publications

(48 reference statements)

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“…Therefore, interstitial pneumonia is considered to be one of the most obvious clinical signs of PRRSV infection, suggesting that the inflammatory response, as well as inflammatory cytokines, plays an important role in this infection and the development of interstitial pneumonia during PRRS (68). However, interestingly, none of these proinflammatory cytokines are released until 7 days after PRRSV challenge, indicating the suppression of the early proinflammatory response in vivo (22,23,34). This is partly attributed to the interruption of the innate immunity by PRRSV (30,31).…”

Section: Discussionmentioning

confidence: 99%

“…Porcine reproductive and respiratory syndrome virus (PRRSV) has ranked among the most important swine pathogens since it was identified in the early 1990s. Most cases of PRRSV infection in vivo display a delayed proinflammatory response (21,22), and high levels of inflammatory cytokines are not released until 7 days after PRRSV challenge, which is attributed to the immunosuppressive effect of the virus (23)(24)(25). PRRSV is a single-stranded RNA virus with an ϳ15-kb genome encoding at least 11 open reading frames (ORFs): ORF1a, ORF1ab, ORF2a, ORF2b, and ORF3 to ORF7 (26).…”

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confidence: 99%

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Porcine Reproductive and Respiratory Syndrome Virus nsp1α Inhibits NF-κB Activation by Targeting the Linear Ubiquitin Chain Assembly Complex

Jing

Fang

Ding

et al. 2017

J Virol

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Linear ubiquitination, a newly discovered posttranslational modification, is catalyzed by the linear ubiquitin chain assembly complex (LUBAC), which is composed of three subunits: one catalytic subunit HOIP and two accessory molecules, HOIL-1L and SHARPIN. Accumulating evidence suggests that linear ubiquitination plays a crucial role in innate immune signaling and especially in the activation of the NF-B pathway by conjugating linear polyubiquitin chains to NF-B essential modulator (NEMO, also called IKK␥), the regulatory subunit of the IKK complex. Porcine reproductive and respiratory syndrome virus (PRRSV), an Arterivirus that has devastated the swine industry worldwide, is an ideal model to study the host's disordered inflammatory responses after viral infection. Here, we found that LUBACinduced NF-B and proinflammatory cytokine expression can be inhibited in the early phase of PRRSV infection. Screening the PRRSV-encoded proteins showed that nonstructural protein 1␣ (nsp1␣) suppresses LUBAC-mediated NF-B activation and its CTE domain is required for the inhibition. Mechanistically, nsp1␣ binds to HOIP/ HOIL-1L and impairs the interaction between HOIP and SHARPIN, thus reducing the LUBAC-dependent linear ubiquitination of NEMO. Moreover, PRRSV infection also blocks LUBAC complex formation and NEMO linear-ubiquitination, the important step for transducing NF-B signaling. This unexpected finding demonstrates a previously unrecognized role of PRRSV nsp1␣ in modulating LUBAC signaling and explains an additional mechanism of immune modulation by PRRSV.IMPORTANCE Porcine reproductive and respiratory syndrome (PRRS) is one of the most important veterinary infectious diseases in countries with intensive swine industries. PRRS virus (PRRSV) infection usually suppresses proinflammatory cytokine expression in the early stage of infection, whereas it induces an inflammatory storm in the late stage. However, precisely how the virus is capable of doing so remains obscure. In this study, we found that by blocking the interaction of its catalytic subunit HOIP and accessory molecule SHARPIN, PRRSV can suppress NF-B signal transduction in the early stage of infection. Our findings not only reveal a novel mechanism evolved by PRRSV to regulate inflammatory responses but also highlight the important role of linear ubiquitination modification during virus infection.KEYWORDS porcine reproductive and respiratory syndrome virus, inflammation, linear ubiquitin chain assembly complex, nonstructural protein 1␣ (nsp1␣)

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Porcine Reproductive and Respiratory Syndrome Virus nsp1α Inhibits NF-κB Activation by Targeting the Linear Ubiquitin Chain Assembly Complex

Jing

Fang

Ding

et al. 2017

J Virol

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“…4-HNE, reactive oxygen species (ROS), reactive nitrogen species (RNS), 15-deoxy-delta-12,14-prostaglandin J2 (15d-PGJ 2 ) are produced in the airways during asthma, COPD and in the esophagus during gastroesophageal reflux disease (GERD) [24] and lastly, toll like receptors (TLRs) that are produced during post viral cough condition. [25,26,27]. Thus, TRPA1 could have a central role in producing chronic cough associated with diverse pathologies but via a common mechanism of vagal nerve activation due to its activators prevailing during specific diseases as described above [9,20,28,29].…”

Section: Trpa1 In Chronic Coughmentioning

confidence: 99%

Blocking TRPA1 in Respiratory Disorders: Does It Hold a Promise?

2016

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Transient Receptor Potential Ankyrin 1 (TRPA1) ion channel is expressed abundantly on the C fibers that innervate almost entire respiratory tract starting from oral cavity and oropharynx, conducting airways in the trachea, bronchi, terminal bronchioles, respiratory bronchioles and upto alveolar ducts and alveoli. Functional presence of TRPA1 on non-neuronal cells got recognized recently. TRPA1 plays a well-recognized role of “chemosensor”, detecting presence of exogenous irritants and endogenous pro-inflammatory mediators that are implicated in airway inflammation and sensory symptoms like chronic cough, asthma, chronic obstructive pulmonary disease (COPD), allergic rhinitis and cystic fibrosis. TRPA1 can remain activated chronically due to elevated levels and continued presence of such endogenous ligands and pro-inflammatory mediators. Several selective TRPA1 antagonists have been tested in animal models of respiratory disease and their performance is very promising. Although there is no TRPA1 antagonist in advanced clinical trials or approved on market yet to treat respiratory diseases, however, limited but promising evidences available so far indicate likelihood that targeting TRPA1 may present a new therapy in treatment of respiratory diseases in near future. This review will focus on in vitro, animal and human evidences that strengthen the proposed role of TRPA1 in modulation of specific airway sensory responses and also on preclinical and clinical progress of selected TRPA1 antagonists.

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“…Upregulation of proinflammatory cytokines by other arteriviruses has also been reported. The pathogenicity of virulent strains of PRRSV was reported to correlate with inflammatory cytokine production (20). EAV infection of equine M⌽s induced upregulation of the mRNAs of a similar set of cytokines (21).…”

Section: Analysis Of Type I Ifn Induction In Shfv-infected Nhp Cellmentioning

confidence: 99%

Differential Responses of Disease-Resistant and Disease-Susceptible Primate Macrophages and Myeloid Dendritic Cells to Simian Hemorrhagic Fever Virus Infection

Vatter

Brinton

2014

J Virol

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Simian hemorrhagic fever virus (SHFV) causes a fatal hemorrhagic fever in macaques but an asymptomatic, persistent infection in baboons. To investigate factors contributing to this differential infection outcome, the targets of SHFV infection, macrophages (M⌽s) and myeloid dendritic cells (mDCs), were differentiated from macaque and baboon peripheral blood monocytes and used to compare viral replication and cell responses. SHFV replicated in >90% of macaque M⌽s but in only ϳ10% of baboon M⌽s. Although SHFV infected ϳ50% of macaque and baboon mDCs, virus replication was efficient in macaque but not in baboon mDCs. Both types of macaque cultures produced higher virus yields than baboon cultures. A more efficient type I interferon response and the production of proinflammatory cytokines, including interleukin-1␤ (IL-1␤), IL-6, IL-12/23(p40), tumor necrosis factor alpha (TNF-␣), and macrophage inflammatory protein 1␣ (MIP-1␣), in response to SHFV infection were observed in macaque but not baboon cultures, suggesting less efficient counteraction of these responses by viral proteins in macaque cells. Baboon cultures produced higher levels of IL-10 than macaque cultures both prior to and after SHFV infection. In baboon but not macaque cell cultures, SHFV infection upregulated IL-10R1, a subunit of the IL-10 receptor (IL-10R), and also SOCS3, a negative regulator of proinflammatory cytokine production. Incubation of macaque cultures with human IL-10 before and/or after SHFV infection decreased production of IL-6, IL-1␤, and MIP-1␣ but not TNF-␣, suggesting a role for IL-10 in suppressing SHFV-induced proinflammatory cytokine production in macaques.

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Comparative expression of Toll-like receptors and inflammatory cytokines in pigs infected with different virulent porcine reproductive and respiratory syndrome virus isolates

Cited by 37 publications

References 34 publications

Porcine Reproductive and Respiratory Syndrome Virus nsp1α Inhibits NF-κB Activation by Targeting the Linear Ubiquitin Chain Assembly Complex

Porcine Reproductive and Respiratory Syndrome Virus nsp1α Inhibits NF-κB Activation by Targeting the Linear Ubiquitin Chain Assembly Complex

Blocking TRPA1 in Respiratory Disorders: Does It Hold a Promise?

Differential Responses of Disease-Resistant and Disease-Susceptible Primate Macrophages and Myeloid Dendritic Cells to Simian Hemorrhagic Fever Virus Infection

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