Regulation and evasion of antiviral immune responses by porcine reproductive and respiratory syndrome virus

Huang, Chen; Zhang, Qiong; Feng, Wen-hai

doi:10.1016/j.virusres.2014.12.014

Cited by 78 publications

(72 citation statements)

References 224 publications

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“…Many potential mechanisms have been proposed to explain how PRRSV employs various strategies to hinder the induction of immune responses and/or evade the effector functions thereafter (Huang et al, 2015). In this study we demonstrated that a pneumo-virulent strain of PRRSV VR2385 down-regulates SLA-I surface expression in PAMs (as an example of natural target cells of PRRSV), PK15-CD163 cells (as an example of peripheral tissue cells), and MoDCs (as antigen-presenting cells, APCs).…”

Section: Discussionmentioning

confidence: 99%

The non-structural protein Nsp2TF of porcine reproductive and respiratory syndrome virus down-regulates the expression of Swine Leukocyte Antigen class I

Cao

Subramaniam

et al. 2016

Virology

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Porcine reproductive and respiratory syndrome virus (PRRSV) is arguably the most economically-important global swine pathogen. Here we demonstrated that PRRSV down-regulates Swine Leukocyte Antigen class I (SLA-I) expression in porcine alveolar macrophages, PK15-CD163 cells and monocyte-derived dendritic cells. To identify the viral protein(s) involved in SLA-I down-regulation, we tested all 22 PRRSV structural and non-structural proteins and identified that Nsp1α and Nsp2TF, and GP3 significantly down-regulated SLA-I expression with Nsp2TF showing the greatest effect. We further generated a panel of mutant viruses in which the Nsp2TF protein synthesis was abolished, and found that the two mutants with disrupted -2 ribosomal frameshifting elements and additional stop codons in the TF domain were unable to down-regulate SLA-I expression. Additionally we demonstrated that the last 68 amino acids of TF domain in Nsp2TF are critical for this function. Collectively, the results indicate a novel function of Nsp2TF in negative modulation of SLA-I expression.

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Section: Discussionmentioning

confidence: 99%

The non-structural protein Nsp2TF of porcine reproductive and respiratory syndrome virus down-regulates the expression of Swine Leukocyte Antigen class I

Cao

Subramaniam

et al. 2016

Virology

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“…PRRSV infection induces poor IFN-I responses, and several PRRSV proteins, including Nsp1, Nsp2, Nsp11, N protein (29,30), and Nsp4 (36,42), were shown to antagonize IFNs. Nsp1 was identified as the most potent antagonist and is able to inhibit the production and signaling of IFN-I.…”

Section: Mir-30c Correlates With Prrsv Infection In Vivomentioning

confidence: 99%

“…The etiological agent of the disease is porcine reproductive and respiratory syndrome virus (PRRSV), an enveloped positive-strand RNA virus that belongs to the Arteriviridae family (28). During PRRSV infection, IFN-I production and signaling are severely crippled (29,30). Recently, several reports showed that many miRNAs are altered by PRRSV, raising the possibility that they are involved in its pathogenesis (31,32).…”

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confidence: 99%

MicroRNA-30c Modulates Type I IFN Responses To Facilitate Porcine Reproductive and Respiratory Syndrome Virus Infection by Targeting JAK1

Zhang

Huang

Yang

et al. 2016

The Journal of Immunology

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Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically important pathogen and has evolved several mechanisms to evade IFN-I responses. We report that a host microRNA, miR-30c, was upregulated by PRRSV via activating NF-κB and facilitated its ability to infect subject animals. Subsequently, we demonstrated that miR-30c was a potent negative regulator of IFN-I signaling by targeting JAK1, resulting in the enhancement of PRRSV infection. In addition, we found that JAK1 expression was significantly decreased by PRRSV and recovered when miR-30c inhibitor was overexpressed. Importantly, miR-30c was also upregulated by PRRSV infection in vivo, and miR-30c expression corresponded well with viral loads in lungs and porcine alveolar macrophages of PRRSV-infected pigs. Our findings identify a new strategy taken by PRRSV to escape IFN-I–mediated antiviral immune responses by engaging miR-30c and, thus, improve our understanding of its pathogenesis.

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“…The lack of anamnestic responses observed following PRRSV exposure in previously vaccinated pigs [6,7] implied that even the well-primed immune system was severely impaired during active PRRSV infection. Numerous reports indicate that PRRSV can evade and suppress host immune responses through several mechanisms [4,[8][9][10][11]. Among these mechanisms, inductions of interleukin-10 http://dx.doi.org/10.1016/j.vaccine.2015.06.020 0264-410X/© 2015 Elsevier Ltd. All rights reserved.…”

Section: Introductionmentioning

confidence: 99%

A novel DNA vaccine for reduction of PRRSV-induced negative immunomodulatory effects: A proof of concept

Suradhat

Wongyanin

Kesdangsakonwut

et al. 2015

Vaccine

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Please cite this article in press as: Suradhat S, et al. A novel DNA vaccine for reduction of PRRSV-induced negative immunomodulatory effects: A proof of concept. Vaccine (2015), http://dx.Keyword: PRRSV DNA vaccine Nucleocapsid protein Tregs a b s t r a c tBackground: Viral-induced interleukin (IL)-10 and regulatory T lymphocytes (Tregs) are believed to play a major role in shaping the immunological and clinical outcomes following Porcine Reproductive and Respiratory Syndrome virus (PRRSV) infection. Recently, it has been shown that PRRSV nucleocapsid (N) protein can induce IL-10 production which is essential for induction of PRRSV-specific Tregs. We hypothesized that immunity to N protein should reduce PRRSV-induced negative immunomodulatory effects which will be essential for establishing proper anti-PRRSV immunity in infected pigs. Objectives: To investigate the immunomodulatory effects of DNA vaccine encoding a linearized, truncated form of PRRSV-N protein (pORF7t) which was designed to preferentially induce cell-mediated immunity against PRRSV N protein.Method: Immunomodulatory effects of the novel DNA vaccine were investigated in an experimental vaccinated-challenged model. In addition, long-term immunomodulatory effects of the DNA vaccine were investigated in vaccinated pigs kept at the PRRSV-positive environment until the end of the fattening period. Pigs were vaccinated either prior to or following natural PRRSV infection. Result: The results indicated that pORF7t could modulate the anti-PRRSV immune responses and promote the control of viral replication in the vaccinated-challenged pigs. Immunized pigs exhibited increased numbers of PRRSV-specific activated CD4 + CD25 + lymphocytes, reduced numbers of PRRSV-specific Tregs, and rapid viral clearance following infection. In a long-term study, regardless of the time of vaccination, DNA vaccine could modulate the host immune responses, resulted in enhanced PRRSV-specific IFN-␥ producing cells, and reduced numbers of PRRSV-specific Tregs, without evidence of enhanced antibody responses. No vaccine adverse reaction was observed throughout the study. Conclusion: This study revealed the novel concept that PRRSV-specific immunity can be modulated by induction of cell-mediated immunity against the nucleocapsid protein. This concept could potentially benefit the development of PRRSV management and control strategies.

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Regulation and evasion of antiviral immune responses by porcine reproductive and respiratory syndrome virus

Cited by 78 publications

References 224 publications

The non-structural protein Nsp2TF of porcine reproductive and respiratory syndrome virus down-regulates the expression of Swine Leukocyte Antigen class I

The non-structural protein Nsp2TF of porcine reproductive and respiratory syndrome virus down-regulates the expression of Swine Leukocyte Antigen class I

MicroRNA-30c Modulates Type I IFN Responses To Facilitate Porcine Reproductive and Respiratory Syndrome Virus Infection by Targeting JAK1

A novel DNA vaccine for reduction of PRRSV-induced negative immunomodulatory effects: A proof of concept

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