Porcine Reproductive and Respiratory Syndrome Virus strains with Higher Virulence Cause Marked Protein Profile Changes in MARC-145 Cells

Chen, Zhi; Liu, Shaoning; Zhang, Shujin; Zhang, Yuyu; Yu, Jiang; Sun, Wenbo; Chen, Lei; Du, Yijun; Wang, Jinbao; Li, Yubao; Wu, Jiaqiang

doi:10.1038/s41598-018-32984-0

Cited by 4 publications

(3 citation statements)

References 54 publications

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“…7 ). In addition, altered proteins are found in other viral infections, including porcine reproductive and respiratory syndrome virus ( 75 ), H5N1 avian influenza viruses ( 76 , 77 ), Japanese encephalitis virus ( 54 ), Rift Valley fever virus ( 78 ), Hepatitis B virus ( 79 ), HIV ( 80 – 82 ), Herpes Simplex virus ( 83 ), and Epstein-Barr virus infection ( Fig. 7B and STRING ontology analysis).…”

Section: Resultsmentioning

confidence: 99%

An Autoantigen Atlas from Human Lung HFL1 Cells Offers Clues to Neurological and Diverse Autoimmune Manifestations of COVID-19

Wang¹,

Zhang

Mw³

et al. 2021

Preprint

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COVID-19 is accompanied by a myriad of both transient and long-lasting autoimmune responses. Dermatan sulfate (DS), a glycosaminoglycan crucial for wound healing, has unique affinity for autoantigens (autoAgs) from apoptotic cells. DS-autoAg complexes are capable of stimulating autoreactive B cells and autoantibody production. Using DS affinity, we identified an autoantigenome of 408 proteins from human fetal lung fibroblast HFL11 cells, at least 231 of which are known autoAgs. Comparing with available COVID data, 352 proteins of the autoantigenome have thus far been found to be altered at protein or RNA levels in SARS-Cov-2 infection, 210 of which are known autoAgs. The COVID-altered proteins are significantly associated with RNA metabolism, translation, vesicles and vesicle transport, cell death, supramolecular fibrils, cytoskeleton, extracellular matrix, and interleukin signaling. They offer clues to neurological problems, fibrosis, smooth muscle dysfunction, and thrombosis. In particular, 150 altered proteins are related to the nervous system, including axon, myelin sheath, neuron projection, neuronal cell body, and olfactory bulb. An association with the melanosome is also identified. The findings from our study illustrate a strong connection between viral infection and autoimmunity. The vast number of COVID-altered proteins with propensity to become autoAgs offers an explanation for the diverse autoimmune complications in COVID patients. The variety of autoAgs related to mRNA metabolism, translation, and vesicles raises concerns about potential adverse effects of mRNA vaccines. The COVID autoantigen atlas we are establishing provides a detailed molecular map for further investigation of autoimmune sequelae of the pandemic.Summary sentenceAn autoantigenome by dermatan sulfate affinity from human lung HFL1 cells may explain neurological and autoimmune manifestations of COVID-19

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Section: Resultsmentioning

confidence: 99%

An Autoantigen Atlas from Human Lung HFL1 Cells Offers Clues to Neurological and Diverse Autoimmune Manifestations of COVID-19

Wang¹,

Zhang

Mw³

et al. 2021

Preprint

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“…Previous studies have explored changes in RNA-seq profile upon PRRSV infection using only one strain, mainly PRRSV-2, and determining these changes by means of microarrays, which have weaknesses relying on existing knowledge about the genome sequence ( 25 , 26 ). Unlike in vivo studies, in vitro approaches present serious difficulties in identifying how the host response interacts with PRRSV, given the impossibility of connecting different cell subpopulations and cellular microenvironments ( 27 – 30 ). Relatively few studies have evaluated RNA-seq changes at tissue level ( 24 ), and besides, most of them conducted the analysis at 1 or 2 time points in a single tissue after PRRSV infection, frequently lymphoid tissues, which are not the main target organ for PRRSV ( 31 , 32 ).…”

Section: Introductionmentioning

confidence: 99%

Time Series Transcriptomic Analysis of Bronchoalveolar Lavage Cells from Piglets Infected with Virulent or Low-Virulent Porcine Reproductive and Respiratory Syndrome Virus 1

Sánchez‐Carvajal

Rodríguez-Gómez

Ruedas‐Torres

et al. 2022

J Virol

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Porcine reproductive and respiratory syndrome virus (PRRSV) has evolved to escape the immune surveillance for a survival advantage leading to a strong modulation of host’s immune responses and favoring secondary bacterial infections. However, limited data are available on how the immunological and transcriptional responses elicited by virulent and low virulent PRRSV-1 strains are comparable and how are them conserved along the infection. To explore the kinetic transcriptional signature associated with the modulation of host immune response at lung level a time-series transcriptomic analysis was performed in bronchoalveolar lavage cells upon experimental in vivo infection with two PRRSV-1 strains of different virulence, virulent subtype 3 Lena strain or the low virulent subtype 1 3249 strain. The time-series analysis revealed overlapping patterns of dysregulated genes enriched in T-cell signaling pathways among both virulent and low-virulent strains, highlighting an up-regulation of co-stimulatory and co-inhibitory immune checkpoints which were disclosed as Hub genes. On the other hand, virulent Lena infection induced an early and more marked “negative regulation of immune system process” with an overexpression of co-inhibitory receptors genes related to T-cell and NK cell functions, in association with more severe lung lesion, lung viral load and BAL cell kinetics. These results underline a complex network of molecular mechanisms governing PRRSV-1 immunopathogenesis at lung level, revealing a pivotal role of co-inhibitory and co-stimulatory immune checkpoints in the pulmonary disease, which may have an impact on T-cell activation and related-pathways. These immune checkpoints together with the regulation of cytokine-signaling pathways, modulated in a virulence-dependent fashion, orchestrate an interplay among pro- and anti-inflammatory responses. Importance: Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the major threats to swine health and global production, causing substantial economic losses. We explore the mechanisms involved in the modulation of host immune response at lung level performing a time-series transcriptomic analysis upon experimental infection with two PRRSV-1 strains of different virulence. A complex network of molecular mechanisms was revealed to control the immunopathogenesis of PRRSV-1 infection, highlighting an interplay among pro- and anti-inflammatory responses as a potential mechanism to restrict inflammation-induced lung injury. Moreover, a pivotal role of co-inhibitory and co-stimulatory immune checkpoints was evidenced, which may lead to progressive dysfunction of T cells, impairing viral clearance and leading to persistent infection, favoring as well secondary bacterial infections or viral rebound. Although further studies should be conducted to evaluate the functional role of immune checkpoints in advanced stages of PRRSV infection and explore a possible T-cell exhaustion state.

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“…20 of these hijacked nuclear proteins are identified by DS-affinity in our study ( Figure 7 ). In addition, altered proteins are found in other viral infections, including porcine reproductive and respiratory syndrome virus ( 275 ), H5N1 avian influenza viruses ( 276 , 277 ), Japanese encephalitis virus ( 254 ), Rift Valley fever virus ( 278 ), Hepatitis B virus ( 279 ), HIV ( 280 – 282 ), Herpes Simplex virus ( 283 ), and Epstein-Barr virus infection ( Figure 7B and STRING ontology analysis). In some cases, viral infections may have both enhancing and protective effects on autoimmunity in type 1 diabetes ( 284 ).…”

Section: Resultsmentioning

confidence: 99%

An Autoantigen Atlas From Human Lung HFL1 Cells Offers Clues to Neurological and Diverse Autoimmune Manifestations of COVID-19

Wang¹,

Zhang

Roehrl³

et al. 2022

Front. Immunol.

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COVID-19 is accompanied by a myriad of both transient and long-lasting autoimmune responses. Dermatan sulfate (DS), a glycosaminoglycan crucial for wound healing, has unique affinity for autoantigens (autoAgs) from apoptotic cells. DS-autoAg complexes are capable of stimulating autoreactive B cells and autoantibody production. We used DS-affinity proteomics to define the autoantigen-ome of lung fibroblasts and bioinformatics analyses to study the relationship between autoantigenic proteins and COVID-induced alterations. Using DS-affinity, we identified an autoantigen-ome of 408 proteins from human HFL1 cells, at least 231 of which are known autoAgs. Comparing with available COVID data, 352 proteins of the autoantigen-ome have thus far been found to be altered at protein or RNA levels in SARS-CoV-2 infection, 210 of which are known autoAgs. The COVID-altered proteins are significantly associated with RNA metabolism, translation, vesicles and vesicle transport, cell death, supramolecular fibrils, cytoskeleton, extracellular matrix, and interleukin signaling. They offer clues to neurological problems, fibrosis, smooth muscle dysfunction, and thrombosis. In particular, 150 altered proteins are related to the nervous system, including axon, myelin sheath, neuron projection, neuronal cell body, and olfactory bulb. An association with the melanosome is also identified. The findings from our study illustrate a connection between COVID infection and autoimmunity. The vast number of COVID-altered proteins with high intrinsic propensity to become autoAgs offers an explanation for the diverse autoimmune complications in COVID patients. The variety of autoAgs related to mRNA metabolism, translation, and vesicles suggests a need for long-term monitoring of autoimmunity in COVID. The COVID autoantigen atlas we are establishing provides a detailed molecular map for further investigation of autoimmune sequelae of the pandemic, such as “long COVID” syndrome.Summary SentenceAn autoantigen-ome by dermatan sulfate affinity from human lung HFL1 cells may explain neurological and autoimmune manifestations of COVID-19.

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Porcine Reproductive and Respiratory Syndrome Virus strains with Higher Virulence Cause Marked Protein Profile Changes in MARC-145 Cells

Cited by 4 publications

References 54 publications

An Autoantigen Atlas from Human Lung HFL1 Cells Offers Clues to Neurological and Diverse Autoimmune Manifestations of COVID-19

An Autoantigen Atlas from Human Lung HFL1 Cells Offers Clues to Neurological and Diverse Autoimmune Manifestations of COVID-19

Time Series Transcriptomic Analysis of Bronchoalveolar Lavage Cells from Piglets Infected with Virulent or Low-Virulent Porcine Reproductive and Respiratory Syndrome Virus 1

An Autoantigen Atlas From Human Lung HFL1 Cells Offers Clues to Neurological and Diverse Autoimmune Manifestations of COVID-19

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