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Article ; Online: SARS-CoV-2 Accessory Proteins in Viral Pathogenesis: Knowns and Unknowns.

Redondo, Natalia / Zaldívar-López, Sara / Garrido, Juan J / Montoya, Maria

2021 Volume 12, Page(s) 708264

Abstract: There are still many unanswered questions concerning viral SARS-CoV-2 pathogenesis in COVID-19. Accessory proteins in SARS-CoV-2 consist of eleven viral proteins whose roles during infection are still not completely understood. Here, a review on the ... ...

Abstract	There are still many unanswered questions concerning viral SARS-CoV-2 pathogenesis in COVID-19. Accessory proteins in SARS-CoV-2 consist of eleven viral proteins whose roles during infection are still not completely understood. Here, a review on the current knowledge of SARS-CoV-2 accessory proteins is summarized updating new research that could be critical in understanding SARS-CoV-2 interaction with the host. Some accessory proteins such as ORF3b, ORF6, ORF7a and ORF8 have been shown to be important IFN-I antagonists inducing an impairment in the host immune response. In addition, ORF3a is involved in apoptosis whereas others like ORF9b and ORF9c interact with cellular organelles leading to suppression of the antiviral response in infected cells. However, possible roles of ORF7b and ORF10 are still awaiting to be described. Also, ORF3d has been reassigned. Relevant information on the knowns and the unknowns in these proteins is analyzed, which could be crucial for further understanding of SARS-CoV-2 pathogenesis and to design strategies counteracting their actions evading immune responses in COVID-19.
MeSH term(s)	COVID-19/immunology ; COVID-19/pathology ; Coronavirus/metabolism ; Coronavirus/pathogenicity ; Humans ; Immune Evasion ; Immunity ; Interferons/antagonists & inhibitors ; SARS-CoV-2/metabolism ; SARS-CoV-2/pathogenicity ; Viral Regulatory and Accessory Proteins/immunology ; Viral Regulatory and Accessory Proteins/metabolism
Chemical Substances	Viral Regulatory and Accessory Proteins ; Interferons (9008-11-1)
Language	English
Publishing date	2021-07-07
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.708264
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Salmonella Typhimurium induces genome-wide expression and phosphorylation changes that modulate immune response, intracellular survival and vesicle transport in infected neutrophils

Zaldívar-López, Sara / Herrera-Uribe, Juber / Bautista, Rocío / Jiménez Soria, Angeles / Moreno, Ángela / Claros, M. Gonzalo / Garrido, Juan J.

Developmental and Comparative Immunology. 2023 Mar., v. 140 p.104597-

2023

Abstract: Salmonella Typhimurium is a food-borne pathogen that causes salmonellosis. When in contact with the host, neutrophils are rapidly recruited to act as first line of defense. To better understand the pathogenesis of this infection, we used an in vitro ... ...

Abstract	Salmonella Typhimurium is a food-borne pathogen that causes salmonellosis. When in contact with the host, neutrophils are rapidly recruited to act as first line of defense. To better understand the pathogenesis of this infection, we used an in vitro model of neutrophil infection to perform dual RNA-sequencing (both host and pathogen). In addition, and given that many pathogens interfere with kinase‐mediated phosphorylation in host signaling, we performed a phosphoproteomic analysis. The immune response was overall diminished in infected neutrophils, mainly JAK/STAT and toll-like receptor signaling pathways. We found decreased expression of proinflammatory cytokine receptor genes and predicted downregulation of the mitogen-activated protein (MAPK) signaling pathway. Also, Salmonella infection inhibited interferons I and II signaling pathways by upregulation of SOCS3 and subsequent downregulation of STAT1 and STAT2. Additionally, phosphorylation of PSMC2 and PSMC4, proteasome regulatory proteins, was decreased in infected neutrophils. Cell viability and survival was increased by p53 signaling, cell cycle arrest and NFkB-proteasome pathways activation. Combined analysis of RNA-seq and phosphoproteomics also revealed inhibited vesicle transport mechanisms mediated by dynein/dynactin and exocyst complexes, involved in ER-to-Golgi transport and centripetal movement of lysosomes and endosomes. Among the overexpressed virulence genes from Salmonella we found potential effectors responsible of these dysregulations, such as spiC, sopD2, sifA or pipB2, all of them involved in intracellular replication. Our results suggest that Salmonella induces (through overexpression of virulence factors) transcriptional and phosphorylation changes that increases neutrophil survival and shuts down immune response to minimize host response, and impairing intracellular vesicle transport likely to keep nutrients for replication and Salmonella-containing vacuole formation and maintenance.
Keywords	Salmonella Typhimurium ; Toll-like receptors ; cell cycle checkpoints ; cell viability ; cytokine receptors ; dynein ATPase ; endosomes ; food pathogens ; immune response ; lysosomes ; models ; neutrophils ; pathogenesis ; phosphorylation ; physiological transport ; proteasome endopeptidase complex ; proteomics ; salmonellosis ; sequence analysis ; transcription (genetics) ; vacuoles ; virulence ; Infection ; Transcriptomics ; Dual RNA-Seq ; Phosphoproteomics
Language	English
Dates of publication	2023-03
Publishing place	Elsevier Ltd
Document type	Article ; Online
ZDB-ID	752411-0
ISSN	1879-0089 ; 0145-305X
ISSN (online)	1879-0089
ISSN	0145-305X
DOI	10.1016/j.dci.2022.104597
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Article ; Online: Study of microRNA expression in Salmonella Typhimurium-infected porcine ileum reveals miR-194a-5p as an important regulator of the TLR4-mediated inflammatory response.

Herrera-Uribe, Juber / Zaldívar-López, Sara / Aguilar, Carmen / Entrenas-García, Carmen / Bautista, Rocío / Claros, M Gonzalo / Garrido, Juan J

Veterinary research

2022 Volume 53, Issue 1, Page(s) 35

Abstract: Infection with Salmonella Typhimurium (S. Typhimurium) is a common cause of food-borne zoonosis leading to acute gastroenteritis in humans and pigs, causing economic losses to producers and farmers, and generating a food security risk. In a previous ... ...

Abstract	Infection with Salmonella Typhimurium (S. Typhimurium) is a common cause of food-borne zoonosis leading to acute gastroenteritis in humans and pigs, causing economic losses to producers and farmers, and generating a food security risk. In a previous study, we demonstrated that S. Typhimurium infection produces a severe transcriptional activation of inflammatory processes in ileum. However, little is known regarding how microRNAs regulate this response during infection. Here, small RNA sequencing was used to identify 28 miRNAs differentially expressed (DE) in ileum of S. Typhimurium-infected pigs, which potentially regulate 14 target genes involved in immune system processes such as regulation of cytokine production, monocyte chemotaxis, or cellular response to interferon gamma. Using in vitro functional and gain/loss of function (mimics/CRISPR-Cas system) approaches, we show that porcine miR-194a-5p (homologous to human miR-194-5p) regulates TLR4 gene expression, an important molecule involved in pathogen virulence, recognition and activation of innate immunity in Salmonella infection.
MeSH term(s)	Animals ; Ileum ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Salmonella Infections, Animal ; Salmonella typhimurium/genetics ; Swine ; Toll-Like Receptor 4/metabolism
Chemical Substances	MicroRNAs ; Toll-Like Receptor 4
Language	English
Publishing date	2022-05-21
Publishing country	England
Document type	Journal Article
ZDB-ID	1146298-x
ISSN	1297-9716 ; 0928-4249
ISSN (online)	1297-9716
ISSN	0928-4249
DOI	10.1186/s13567-022-01056-7
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Article ; Online: Salmonella Typhimurium induces genome-wide expression and phosphorylation changes that modulate immune response, intracellular survival and vesicle transport in infected neutrophils.

Zaldívar-López, Sara / Herrera-Uribe, Juber / Bautista, Rocío / Jiménez, Ángeles / Moreno, Ángela / Claros, M Gonzalo / Garrido, Juan J

Developmental and comparative immunology

2022 Volume 140, Page(s) 104597

Abstract	Salmonella Typhimurium is a food-borne pathogen that causes salmonellosis. When in contact with the host, neutrophils are rapidly recruited to act as first line of defense. To better understand the pathogenesis of this infection, we used an in vitro model of neutrophil infection to perform dual RNA-sequencing (both host and pathogen). In addition, and given that many pathogens interfere with kinase-mediated phosphorylation in host signaling, we performed a phosphoproteomic analysis. The immune response was overall diminished in infected neutrophils, mainly JAK/STAT and toll-like receptor signaling pathways. We found decreased expression of proinflammatory cytokine receptor genes and predicted downregulation of the mitogen-activated protein (MAPK) signaling pathway. Also, Salmonella infection inhibited interferons I and II signaling pathways by upregulation of SOCS3 and subsequent downregulation of STAT1 and STAT2. Additionally, phosphorylation of PSMC2 and PSMC4, proteasome regulatory proteins, was decreased in infected neutrophils. Cell viability and survival was increased by p53 signaling, cell cycle arrest and NFkB-proteasome pathways activation. Combined analysis of RNA-seq and phosphoproteomics also revealed inhibited vesicle transport mechanisms mediated by dynein/dynactin and exocyst complexes, involved in ER-to-Golgi transport and centripetal movement of lysosomes and endosomes. Among the overexpressed virulence genes from Salmonella we found potential effectors responsible of these dysregulations, such as spiC, sopD2, sifA or pipB2, all of them involved in intracellular replication. Our results suggest that Salmonella induces (through overexpression of virulence factors) transcriptional and phosphorylation changes that increases neutrophil survival and shuts down immune response to minimize host response, and impairing intracellular vesicle transport likely to keep nutrients for replication and Salmonella-containing vacuole formation and maintenance.
MeSH term(s)	Animals ; Salmonella typhimurium ; Neutrophils/metabolism ; Phosphorylation ; Proteasome Endopeptidase Complex/metabolism ; Salmonella Infections ; Immunity ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism
Chemical Substances	Proteasome Endopeptidase Complex (EC 3.4.25.1) ; Bacterial Proteins
Language	English
Publishing date	2022-11-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	752411-0
ISSN	1879-0089 ; 0145-305X
ISSN (online)	1879-0089
ISSN	0145-305X
DOI	10.1016/j.dci.2022.104597
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Article: Study of microRNA expression in Salmonella Typhimurium-infected porcine ileum reveals miR-194a-5p as an important regulator of the TLR4-mediated inflammatory response

Herrera-Uribe, Juber / Zaldívar-López, Sara / Aguilar, Carmen / Entrenas-García, Carmen / Bautista, Rocío / Claros, M. Gonzalo / Garrido, Juan J.

Veterinary research. 2022 Dec., v. 53, no. 1

2022

Abstract	Infection with Salmonella Typhimurium (S. Typhimurium) is a common cause of food-borne zoonosis leading to acute gastroenteritis in humans and pigs, causing economic losses to producers and farmers, and generating a food security risk. In a previous study, we demonstrated that S. Typhimurium infection produces a severe transcriptional activation of inflammatory processes in ileum. However, little is known regarding how microRNAs regulate this response during infection. Here, small RNA sequencing was used to identify 28 miRNAs differentially expressed (DE) in ileum of S. Typhimurium-infected pigs, which potentially regulate 14 target genes involved in immune system processes such as regulation of cytokine production, monocyte chemotaxis, or cellular response to interferon gamma. Using in vitro functional and gain/loss of function (mimics/CRISPR-Cas system) approaches, we show that porcine miR-194a-5p (homologous to human miR-194-5p) regulates TLR4 gene expression, an important molecule involved in pathogen virulence, recognition and activation of innate immunity in Salmonella infection.
Keywords	Salmonella Typhimurium ; chemotaxis ; cytokines ; food security ; gastroenteritis ; gene expression ; humans ; ileum ; inflammation ; innate immunity ; interferon-gamma ; microRNA ; monocytes ; pathogens ; risk ; salmonellosis ; swine ; transcriptional activation ; veterinary medicine ; virulence ; zoonoses
Language	English
Dates of publication	2022-12
Size	p. 35.
Publishing place	BioMed Central
Document type	Article
ZDB-ID	1146298-x
ISSN	1297-9716 ; 0928-4249
ISSN (online)	1297-9716
ISSN	0928-4249
DOI	10.1186/s13567-022-01056-7
Database	NAL-Catalogue (AGRICOLA)

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Article: The Effect of Atopic Dermatitis and Diet on the Skin Transcriptome in Staffordshire Bull Terriers.

Anturaniemi, Johanna / Zaldívar-López, Sara / Savelkoul, Huub F J / Elo, Kari / Hielm-Björkman, Anna

Frontiers in veterinary science

2020 Volume 7, Page(s) 552251

Abstract: Canine atopic dermatitis (CAD) has a hereditary basis that is modified by interactions with the environment, including diet. Differentially expressed genes in non-lesional skin, determined by RNA sequencing before and after a dietary intervention, were ... ...

Abstract	Canine atopic dermatitis (CAD) has a hereditary basis that is modified by interactions with the environment, including diet. Differentially expressed genes in non-lesional skin, determined by RNA sequencing before and after a dietary intervention, were compared between dogs with naturally occurring CAD (
Language	English
Publishing date	2020-10-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2834243-4
ISSN	2297-1769
ISSN	2297-1769
DOI	10.3389/fvets.2020.552251
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Article: Owners’ perception of acquiring infections through raw pet food: a comprehensive internet‐based survey

Anturaniemi, Johanna / Barrouin‐Melo, Stella Maria / Zaldivar‐López, Sara / Sinkko, Hanna / Hielm‐Björkman, Anna

Veterinary record. 2019 Nov., v. 185, no. 21

2019

Abstract: There has been concerns related to the risk of bacterial contamination from raw pet food to humans, but research is still scarce. The purpose of this cross‐sectional study was to use a worldwide internet survey‐based data to evaluate the impact of raw ... ...

Abstract	There has been concerns related to the risk of bacterial contamination from raw pet food to humans, but research is still scarce. The purpose of this cross‐sectional study was to use a worldwide internet survey‐based data to evaluate the impact of raw pet foods on human health from the owners’ experience. From 16 475 households, 0.2 per cent (n=39) reported having had a transmission of pathogen from the raw pet food to a human family member during the time that raw feeding had been used in the household. Only in three of those households the same pathogen that was found in the human sample was analysed and confirmed also in the raw pet food (0.02 per cent of all data). Moreover, 0.1 per cent (n=24) reported suspecting that a disease could have been transmitted to a human from the pet food. Feeding salmon and turkey, using more than 50 per cent of the diet as raw foods and preparing the raw food in the same place and utensils as the family foods all had negative association with infections. Having 2 to 6 year‐old children living in the household was associated with more infections, although adults were the most frequently infected.
Keywords	Internet ; bacterial contamination ; cross-sectional studies ; diet ; human health ; humans ; pathogens ; pet foods ; raw foods ; risk ; salmon ; surveys
Language	English
Dates of publication	2019-11
Size	p. 658.
Publishing place	BMJ Publishing Group Limited
Document type	Article
Note	JOURNAL ARTICLE
ZDB-ID	390015-0
ISSN	2042-7670 ; 0042-4900
ISSN (online)	2042-7670
ISSN	0042-4900
DOI	10.1136/vr.105122
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Article ; Online: Owners' perception of acquiring infections through raw pet food: a comprehensive internet-based survey.

Anturaniemi, Johanna / Barrouin-Melo, Stella Maria / Zaldivar-López, Sara / Sinkko, Hanna / Hielm-Björkman, Anna

The Veterinary record

2019 Volume 185, Issue 21, Page(s) 658

Abstract: There has been concerns related to the risk of bacterial contamination from raw pet food to humans, but research is still scarce. The purpose of this cross-sectional study was to use a worldwide internet survey-based data to evaluate the impact of raw ... ...

Abstract	There has been concerns related to the risk of bacterial contamination from raw pet food to humans, but research is still scarce. The purpose of this cross-sectional study was to use a worldwide internet survey-based data to evaluate the impact of raw pet foods on human health from the owners' experience. From 16 475 households, 0.2 per cent (n=39) reported having had a transmission of pathogen from the raw pet food to a human family member during the time that raw feeding had been used in the household. Only in three of those households the same pathogen that was found in the human sample was analysed and confirmed also in the raw pet food (0.02 per cent of all data). Moreover, 0.1 per cent (n=24) reported suspecting that a disease could have been transmitted to a human from the pet food. Feeding salmon and turkey, using more than 50 per cent of the diet as raw foods and preparing the raw food in the same place and utensils as the family foods all had negative association with infections. Having 2 to 6 year-old children living in the household was associated with more infections, although adults were the most frequently infected.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Animal Feed/adverse effects ; Animals ; Cross-Sectional Studies ; Female ; Humans ; Infections/etiology ; Internet ; Male ; Middle Aged ; Ownership ; Perception ; Raw Foods/adverse effects ; Surveys and Questionnaires ; Young Adult
Language	English
Publishing date	2019-08-19
Publishing country	England
Document type	Journal Article
ZDB-ID	390015-0
ISSN	2042-7670 ; 0042-4900
ISSN (online)	2042-7670
ISSN	0042-4900
DOI	10.1136/vr.105122
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Article ; Online: SARS-CoV-2 accessory proteins involvement in inflammatory and profibrotic processes through IL11 signaling.

López-Ayllón, Blanca D / de Lucas-Rius, Ana / Mendoza-García, Laura / García-García, Tránsito / Fernández-Rodríguez, Raúl / Suárez-Cárdenas, José M / Santos, Fátima Milhano / Corrales, Fernando / Redondo, Natalia / Pedrucci, Federica / Zaldívar-López, Sara / Jiménez-Marín, Ángeles / Garrido, Juan J / Montoya, María

Frontiers in immunology

2023 Volume 14, Page(s) 1220306

Abstract: SARS-CoV-2, the cause of the COVID-19 pandemic, possesses eleven accessory proteins encoded in its genome. Their roles during infection are still not completely understood. In this study, transcriptomics analysis revealed that ... ...

Abstract	SARS-CoV-2, the cause of the COVID-19 pandemic, possesses eleven accessory proteins encoded in its genome. Their roles during infection are still not completely understood. In this study, transcriptomics analysis revealed that both
MeSH term(s)	Humans ; COVID-19 ; Interleukin-11 ; SARS-CoV-2/genetics ; Viral Proteins/genetics ; Idiopathic Pulmonary Fibrosis
Chemical Substances	Interleukin-11 ; Viral Proteins
Language	English
Publishing date	2023-07-20
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1220306
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Article ; Online: Impairment of antiviral immune response and disruption of cellular functions by SARS-CoV-2 ORF7a and ORF7b.

García-García, Tránsito / Fernández-Rodríguez, Raúl / Redondo, Natalia / de Lucas-Rius, Ana / Zaldívar-López, Sara / López-Ayllón, Blanca Dies / Suárez-Cárdenas, José M / Jiménez-Marín, Ángeles / Montoya, María / Garrido, Juan J

iScience

2022 Volume 25, Issue 11, Page(s) 105444

Abstract: SARS-CoV-2, the causative agent of the present COVID-19 pandemic, possesses eleven accessory proteins encoded in its genome, and some have been implicated in facilitating infection and pathogenesis through their interaction with cellular components. ... ...

Abstract	SARS-CoV-2, the causative agent of the present COVID-19 pandemic, possesses eleven accessory proteins encoded in its genome, and some have been implicated in facilitating infection and pathogenesis through their interaction with cellular components. Among these proteins, accessory protein ORF7a and ORF7b functions are poorly understood. In this study, A549 cells were transduced to express ORF7a and ORF7b, respectively, to explore more in depth the role of each accessory protein in the pathological manifestation leading to COVID-19. Bioinformatic analysis and integration of transcriptome results identified defined canonical pathways and functional groupings revealing that after expression of ORF7a or ORF7b, the lung cells are potentially altered to create conditions more favorable for SARS-CoV-2, by inhibiting the IFN-I response, increasing proinflammatory cytokines release, and altering cell metabolic activity and adhesion. Based on these results, it is plausible to suggest that ORF7a or ORF7b could be used as biomarkers of progression in this pandemic.
Language	English
Publishing date	2022-10-25
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2022.105444
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