scholarly journals Virulent Pseudorabies Virus Infection Induces a Specific and Lethal Systemic Inflammatory Response in Mice

2018 ◽  
Vol 92 (24) ◽  
Author(s):  
K. Laval ◽  
J. B. Vernejoul ◽  
J. Van Cleemput ◽  
O. O. Koyuncu ◽  
L. W. Enquist
Keyword(s):  
Nervous System ◽  
Clinical Outcome ◽  
Inflammatory Response ◽  
Plasma Levels ◽  
Pseudorabies Virus ◽  
Virulent Strain ◽  
Systemic Inflammatory Response ◽  
Natural Host ◽  
Human Pathogens ◽  
Monocyte Chemoattractant Protein 1

ABSTRACTPseudorabies virus (PRV) is an alphaherpesvirus that infects the peripheral nervous system (PNS). The natural host of PRV is the swine, but it can infect most mammals, including cattle, rodents, and dogs. In these nonnatural hosts, PRV always causes a severe acute and lethal neuropathy called the “mad itch,” which is uncommon in swine. Thus far, the pathophysiological and immunological processes leading to the development of the neuropathic itch and the death of the animal are unclear. Using a footpad inoculation model, we established that mice inoculated with PRV-Becker (virulent strain) develop a severe pruritus in the foot and become moribund at 82 h postinoculation (hpi). We found necrosis and inflammation with a massive neutrophil infiltration only in the footpad and dorsal root ganglia (DRGs) by hematoxylin and eosin staining. PRV load was detected in the foot, PNS, and central nervous system tissues by quantitative reverse transcription-PCR. Infected mice had elevated plasma levels of proinflammatory cytokines (interleukin-6 [IL-6] and granulocyte colony-stimulating factor [G-CSF]) and chemokines (Gro-1 and monocyte chemoattractant protein 1). Significant IL-6 and G-CSF levels were detected in several tissues at 82 hpi. High plasma levels of C-reactive protein confirmed the acute inflammatory response to PRV-Becker infection. Moreover, mice inoculated with PRV-Bartha (attenuated, live vaccine strain) did not develop pruritus at 82 hpi. PRV-Bartha also replicated in the PNS, and the infection spread further in the brain than PRV-Becker. PRV-Bartha infection did not induce the specific and lethal systemic inflammatory response seen with PRV-Becker. Overall, we demonstrated the importance of inflammation in the clinical outcome of PRV infection in mice and provide new insights into the process of PRV-induced neuroinflammation.IMPORTANCEPseudorabies virus (PRV) is an alphaherpesvirus related to human pathogens such as herpes simplex virus 1 and varicella-zoster virus (VZV). The natural host of PRV is the swine, but it can infect most mammals. In susceptible animals other than pigs, PRV infection always causes a characteristic lethal pruritus known as the “mad itch.” The role of the immune response in the clinical outcome of PRV infection is still poorly understood. Here, we show that a systemic host inflammatory response is responsible for the severe pruritus and acute death of mice infected with virulent PRV-Becker but not mice infected with attenuated strain PRV-Bartha. In addition, we identified IL-6 and G-CSF as two main cytokines that play crucial roles in the regulation of this process. Our findings give new insights into neuroinflammatory diseases and strengthen further the similarities between VZV and PRV infections at the level of innate immunity.

scholarly journals Systemic inflammatory response syndrome and multiple-organ damage / dysfunction in complicated canine babesiosis

2001 ◽  
Vol 72 (3) ◽  
Author(s):  
C. Welzl ◽  
A.L. Leisewitz ◽  
L.S. Jacobson ◽  
T. Vaughan-Scott ◽  
E. Myburgh
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Systemic Inflammatory Response Syndrome ◽  
Inflammatory Response ◽  
Renal Involvement ◽  
Organ Damage ◽  
Multiple Organ ◽  
Systemic Inflammatory Response ◽  
The Body ◽  
Increased Risk

This study was designed to document the systemic inflammatory response syndrome (SIRS) and multiple-organ dysfunction syndrome (MODS) in dogs with complicated babesiosis, and to assess their impact on outcome. Ninety-one cases were evaluated retro-spectively for SIRS and 56 for MODS. The liver, kidneys, lungs, central nervous system and musculature were assessed. Eighty-seven percent of cases were SIRS-positive. Fifty-two percent of the cases assessed for organ damage had single-organ damage and 48 % had MODS. Outcome was not significantly affected by either SIRS or MODS, but involvement of specific organs had a profound effect. Central nervous system involvement resulted in a 57 times greater chance of death and renal involvement in a 5-fold increased risk compared to all other complications. Lung involvement could not be statistically evaluated owing to co-linearity with other organs, but was associated with high mortality. Liver and muscle damage were common, but did not significantly affect outcome. There are manysimilarities between the observations in this study and previous human and animal studies in related fields, lending additional support to the body of evidence for shared underlying pathophysiological mechanisms in systemic inflammatory states.

scholarly journals Presence of Systemic Inflammatory Response Syndrome Predicts a Poor Clinical Outcome in Dogs with a Primary Hepatitis

PLoS ONE ◽  
2016 ◽  
Vol 11 (1) ◽  
pp. e0146560 ◽  
Author(s):  
Scott Kilpatrick ◽  
Margaret Dreistadt ◽  
Polly Frowde ◽  
Roger Powell ◽  
Elspeth Milne ◽  
...  
Keyword(s):  
Systemic Inflammatory Response Syndrome ◽  
Clinical Outcome ◽  
Inflammatory Response ◽  
Systemic Inflammatory Response ◽  
Poor Clinical Outcome

scholarly journals Diagnostic value of monocyte chemoattractant Protein-1, soluble mannose receptor, Presepsin, and Procalcitonin in critically ill children admitted with suspected sepsis

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Noha A. Hassuna ◽  
Ebtesam Elgezawy ◽  
Suzan O. Mousa ◽  
Reem A. AbdelAziz ◽  
Reham A. Ibrahem ◽  
...  
Keyword(s):  
Systemic Inflammatory Response Syndrome ◽  
Inflammatory Response ◽  
Critically Ill ◽  
Mannose Receptor ◽  
Diagnostic Value ◽  
Systemic Inflammatory Response ◽  
Critically Ill Children ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Monocyte Chemoattractant Protein

Abstract Introduction The differentiation between systemic inflammatory response syndrome and sepsis is very important as it determines essential treatment decisions, such as selection, initiation, and duration of antibiotic therapy. Objectives We aimed to investigate the diagnostic value of Procalcitonin, Monocyte Chemoattractant Protein-1, soluble Mannose Receptor, Presepsin as early biomarkers of pediatric sepsis in comparison to systemic inflammatory response syndrome in severely ill children. Patients and methods This study included 58 children diagnosed as sepsis (group 1), 24 children with systemic inflammatory response syndrome without infection (group 2), and 50 healthy children as controls (group 3). All the plasma levels of the studied biomarkers were measured and ROC curves were created for all the tested parameters to discriminate between sepsis and SIRS. Results The area under the curve for Monocyte Chemoattractant Protein-1 was 0.926 (0.846-0.927) with sensitivity 100% and specificity 62.5%. The soluble Mannose Receptor had the highest sensitivity (100%), with AUC equals 1(.0.956-1.0) and specificity of 100%. The cut-off values for Procalcitonin, Presepsin, soluble Mannose Receptor, and Monocyte Chemoattractant Protein-1 and were: 0.62 ng/ml, 100 pg/ml, 13 ng/ml and 90 pg/ml, respectively. In septic cases, both soluble Mannose Receptor and Procalcitonin have positive correlations with the severity of sepsis, low Glasgow Coma Scale, ventilatory support, use of inotropic drugs and mortality rate (r = 0.950, 0.812, 0.795, 0.732 and 0.861respectively) for soluble Mannose Receptor and (0.536, 0.473, 0.422, 0.305 and 0.474 respectively) for Procalcitonin. Conclusion Soluble Mannose Receptor, Presepsin, and Monocyte Chemoattractant Protein-1 can be used to differentiate between sepsis and SIRS in critically ill children.

Thalidomide decreases the plasma levels of IL-1 and TNF following burn injury: Is it a new drug for modulation of systemic inflammatory response

Burns ◽  
2008 ◽  
Vol 34 (1) ◽  
pp. 104-108 ◽  
Author(s):  
Muhitdin Eski ◽  
Ismail Sahin ◽  
Mustafa Sengezer ◽  
Muhittin Serdar ◽  
Ahmet Ifran
Keyword(s):  
Inflammatory Response ◽  
Plasma Levels ◽  
Burn Injury ◽  
Systemic Inflammatory Response ◽  
New Drug

scholarly journals Pseudorabies Virus Infection Accelerates Degradation of the Kinesin-3 Motor KIF1A

2020 ◽  
Vol 94 (9) ◽  
Author(s):  
Hao Huang ◽  
Orkide O. Koyuncu ◽  
Lynn W. Enquist
Keyword(s):  
Nervous System ◽  
Peripheral Nervous System ◽  
Pseudorabies Virus ◽  
Time Window ◽  
Proteasomal Degradation ◽  
Neuronal Cultures ◽  
Human Pathogens ◽  
Herpes Simplex Viruses ◽  
Varicella Zoster ◽  
Axonal Sorting

ABSTRACT Alphaherpesviruses, including pseudorabies virus (PRV), are neuroinvasive pathogens that establish lifelong latency in peripheral ganglia following the initial infection at mucosal surfaces. The establishment of latent infection and subsequent reactivations, during which newly assembled virions are sorted into and transported anterogradely inside axons to the initial mucosal site of infection, rely on axonal bidirectional transport mediated by microtubule-based motors. Previous studies using cultured peripheral nervous system (PNS) neurons have demonstrated that KIF1A, a kinesin-3 motor, mediates the efficient axonal sorting and transport of newly assembled PRV virions. Here we report that KIF1A, unlike other axonal kinesins, is an intrinsically unstable protein prone to proteasomal degradation. Interestingly, PRV infection of neuronal cells leads not only to a nonspecific depletion of KIF1A mRNA but also to an accelerated proteasomal degradation of KIF1A proteins, leading to a near depletion of KIF1A protein late in infection. Using a series of PRV mutants deficient in axonal sorting and anterograde spread, we identified the PRV US9/gE/gI protein complex as a viral factor facilitating the proteasomal degradation of KIF1A proteins. Moreover, by using compartmented neuronal cultures that fluidically and physically separate axons from cell bodies, we found that the proteasomal degradation of KIF1A occurs in axons during infection. We propose that the PRV anterograde sorting complex, gE/gI/US9, recruits KIF1A to viral transport vesicles for axonal sorting and transport and eventually accelerates the proteasomal degradation of KIF1A in axons. IMPORTANCE Pseudorabies virus (PRV) is an alphaherpesvirus related to human pathogens herpes simplex viruses 1 and 2 and varicella-zoster virus. Alphaherpesviruses are neuroinvasive pathogens that establish lifelong latent infections in the host peripheral nervous system (PNS). Following reactivation from latency, infection spreads from the PNS back via axons to the peripheral mucosal tissues, a process mediated by kinesin motors. Here, we unveil and characterize the underlying mechanisms for a PRV-induced, accelerated degradation of KIF1A, a kinesin-3 motor promoting the sorting and transport of PRV virions in axons. We show that PRV infection disrupts the synthesis of KIF1A and simultaneously promotes the degradation of intrinsically unstable KIF1A proteins by proteasomes in axons. Our work implies that the timing of motor reduction after reactivation would be critical because progeny particles would have a limited time window for sorting into and transport in axons for further host-to-host spread.

Can systemic inflammatory response syndrome score at admission predict clinical outcome in patients with severe burns?

Burns ◽  
2019 ◽  
Vol 45 (4) ◽  
pp. 860-868
Author(s):  
Guosheng Wu ◽  
Mingzhu Zhuang ◽  
Yong Jiang ◽  
Junhao Fan ◽  
Yifang Sun ◽  
...  
Keyword(s):  
Systemic Inflammatory Response Syndrome ◽  
Clinical Outcome ◽  
Inflammatory Response ◽  
Systemic Inflammatory Response ◽  
Severe Burns
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