Porcine reproductive and respiratory syndrome virus and bacterial endotoxin act in synergy to amplify the inflammatory response of infected macrophages

Qiao, Songlin; Li, Feng; Bao, Dan; Guo, Junqing; Wan, Bo; Xiao, Zhijun; Yang, Suzhen; Zhang, Gaiping

doi:10.1016/j.vetmic.2010.11.006

Cited by 63 publications

(49 citation statements)

References 29 publications

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“…Qiao et al (57) showed that HP-PRRSV HN07-1 strain infection induces much more IL-1b from naive PAMs compared with the lower virulent PRRSV BJ-4 strain infection. Consistent with these results, we found that highly virulent strains (e.g., HuN4 and SDA2 strains) induced significantly higher levels of proinflammatory cytokines (such as IL-1b and TNF-a) than the lower virulent strains (e.g., CH1a, CH1R, and HuN4-F112 strains) did (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…A previous study revealed that the HP-PRRSV-infected PAMs produce higher level of IL-1b compared with the lower virulent PRRSV-infected PAMs (57). To test whether PRRSV infectioninduced inflammatory responses depend on the properties of the specific PRRSV strains, PAMs were infected with different PRRSV strains, and the IL-1b and TNF-a mRNA expressions and secretions were detected by qRT-PCR and ELISA, respectively.…”

Section: Hp-prrsv Infection Induces Nlrp3-dependent Inflammasome Actimentioning

confidence: 99%

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DDX19A Senses Viral RNA and Mediates NLRP3-Dependent Inflammasome Activation

Liu

et al. 2015

The Journal of Immunology

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The NLRP3 inflammasome plays a major role in innate immune responses by activating caspase-1, resulting in secretion of IL-1β and inflammatory pathologic responses. Viral RNA can induce NLRP3 inflammasome activation. However, none of the components of NLRP3 inflammasome has the ability to bind viral RNA. Therefore, it had been proposed that there might have been some unidentified cytosolic RNA sensors that could bind viral RNA and NLRP3 to initiate NLRP3 inflammasome activation. In this study, DDX19A, a member of the DEAD/H-box protein family, was identified as a novel component of NLRP3 inflammasome using arterivirus infection as a model. We found that DDX19A interacted with viral RNA and NLRP3. Knockdown of DDX19A expression efficiently inhibited procaspase-1 cleavage and IL-1β secretion in porcine reproductive and respiration syndrome virus (PRRSV)–infected or PRRSV RNA-stimulated primary porcine alveolar macrophages. Overall, DDX19A was identified as a novel cytosolic RNA sensor that bridged PRRSV RNA and NLRP3 to activate NLRP3 inflammasome.

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Section: Discussionmentioning

confidence: 99%

Section: Hp-prrsv Infection Induces Nlrp3-dependent Inflammasome Actimentioning

confidence: 99%

DDX19A Senses Viral RNA and Mediates NLRP3-Dependent Inflammasome Activation

Liu

et al. 2015

The Journal of Immunology

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“…AF331831, isolated in 1996 in China and kindly provided by Hanchun Yang of China Agricultural University, China) and HP-PRRSV strain HN07-1 (isolated during an HP-PRRSV outbreak in Henan province of China in 2007 by our laboratory) were used in this study and prepared according to our laboratory's previous study (70).…”

Section: Methodsmentioning

confidence: 99%

The Crystal Structure of the Fifth Scavenger Receptor Cysteine-Rich Domain of Porcine CD163 Reveals an Important Residue Involved in Porcine Reproductive and Respiratory Syndrome Virus Infection

Jiang

Qiao

et al. 2017

J Virol

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Porcine reproductive and respiratory syndrome (PRRS) has become an economically critical factor in swine industry since its worldwide spread in the 1990s. Infection by its causative agent, PRRS virus (PRRSV), was proven to be mediated by an indispensable receptor, porcine CD163 (pCD163), and the fifth scavenger receptor cysteine-rich domain (SRCR5) is essential for virus infection. However, the structural details and specific residues of pCD163 SRCR5 involved in infection have not been defined yet. In this study, we prepared recombinant pCD163 SRCR5 in Drosophila melanogaster Schneider 2 (S2) cells and determined its crystal structure at a high resolution of 2.0 Å. This structure includes a markedly long loop region and shows a special electrostatic potential, and these are significantly different from those of other members of the scavenger receptor cysteine-rich superfamily (SRCR-SF). Subsequently, we carried out structure-based mutational studies to identify that the arginine residue at position 561 (Arg561) in the long loop region is important for PRRSV infection. Further, we showed Arg561 probably takes effect on the binding of pCD163 to PRRSV during virus invasion. Altogether the current work provides the first view of the CD163 SRCR domain, expands our knowledge of the invasion mechanism of PRRSV, and supports a molecular basis for prevention and control of the virus.IMPORTANCE PRRS has caused huge economic losses to pig farming. The syndrome is caused by PRRSV, and PRRSV infection has been shown to be mediated by host cell surface receptors. One of them, pCD163, is especially indispensable, and its SRCR5 domain has been further demonstrated to play a significant role in virus infection. However, its structural details and the residues involved in infection are unknown. In this study, we determined the crystal structure of pCD163 SRCR5 and then carried out site-directed mutational studies based on the crystal structure to elucidate which residue is important. Our work not only provides structural information on the CD163 SRCR domain for the first time but also indicates the molecular mechanism of PRRSV infection and lays a foundation for future applications in prevention and control of PRRS.KEYWORDS CD163, Drosophila S2 cells, PRRSV, SRCR5, crystal structure P orcine reproductive and respiratory syndrome (PRRS) was first reported in 1987 in the United States (1) and has become a critical economic factor in the swine industry since its worldwide spread in the 1990s (2, 3). PRRS is characterized by

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“…It has recently been shown that upregulation of pro-inflammatory cytokine production by PRRSVinfected PAMs in vitro was further elevated by addition of LPS. The elevated pro-inflammatory cytokine production has been attributed to the increase of CD14 (the primary LPS receptor) on PRRSVinfected PAMs (Qiao et al, 2011). An earlier study showing elevated numbers of lung macrophages with increased expression of CD14 in PRRSV infected animals (Van Gucht et al, 2005) supports this hypothesis.…”

Section: Introductionmentioning

confidence: 99%