Cellular Stress Response to Varicella-Zoster Virus Infection of Human Skin Includes Highly Elevated Interleukin-6 Expression

Jarosinski, Keith W.; Carpenter, John E.; Buckingham, Erin M.; Jackson, Wallen; Knudtson, Kevin L.; Moffat, Jennifer F.; Kita, Hirohito; Grose, Charles

doi:10.1093/ofid/ofy118

Cited by 25 publications

(30 citation statements)

References 42 publications

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“…Interestingly, we demonstrated a very high IL-6 protein levels (ϳ30,000 pg/ml) in the footpad of PRV-Becker-infected mice. This result strongly correlates with a recent study, which demonstrated the same exact concentration of IL-6 in human skin explant cultures after VZV infection (27). Thus, these findings support the fact that VZV and PRV have very similar innate immune responses to infection of skin.…”

Section: Discussionsupporting

confidence: 91%

See 1 more Smart Citation

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

Laval

Vernejoul

Cleemput

et al. 2018

J Virol

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Pseudorabies 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.IMPORTANCE Pseudorabies 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. Citation Laval K, Vernejoul JB, Van Cleemput J, Koyuncu OO, Enquist LW. 2018. Virulent pseudorabies virus infection induces a specific and lethal systemic inflammatory response in mice. J Virol 92:e01614-18. https://doi.org/10 .1128/JVI.01614-18. Editor Ric...

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Section: Discussionsupporting

confidence: 91%

“…Similar lethal systemic inflammatory responses have also been reported during dengue virus, Sindbis virus, and SARS-CoV infections (24)(25)(26). Interestingly, a recent study also demonstrated that VZV infection induces high levels of IL-6 transcription and protein production in human skin explant cultures (27).…”

Section: Introductionsupporting

confidence: 67%

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

Laval

Vernejoul

Cleemput

et al. 2018

J Virol

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“…VZV is highly contagious and can be transmitted through respiratory droplets or direct contact with infected skin lesions [9][10][11]. VZV is neurotropic and which can be lurking in the neurons of the posterior root ganglia of the spinal cord for a long time after infection.…”

Section: Discussionmentioning

confidence: 99%

Clinical and magnetic resonance analysis of varicella-zoster virus (VZV) transcranial nerve into brain-induced brainstem encephalitis

Han

Xie

Kang

et al. 2019

Preprint

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Background: In this study, we summarize the clinical and magnetic resonance characteristics of patients with varicella-zoster virus transcranial brain-induced brainstem encephalitis. Methods: The patient's baseline data meet the inclusion criteria were collected. All patients were admitted to the hospital for routine blood, urine, and stool, blood glucose, blood pressure, blood lipids, homocysteine, liver function, renal function, electrolytes, eight items before the operation, autoantibodies, 24-hour dynamic EEG. All patients underwent a head MRI scan, and the patients underwent lumbar puncture, perfecting routine cerebrospinal fluid, biochemical and cytological examinations, and high-throughput examination of cerebrospinal fluid pathogens. Result: Seven patients were enrolled in this study. All patients were associated with skin herpes in the area of cranial nerve distribution. Herpes is complicated with V-cranial nerve in 1 case, facial nerve (6 cases), vestibular nerve (5 cases), tongue pharynx, vagus nerve (1 case). The interval of central nervous system injury after 6 cases of skin herpes were 3-20 days. Laboratory and EEG examinations showed that all patients had no abnormalities in autoantibodies and preoperative eight items; low blood routines showed elevated white blood cells in 4 cases, elevated blood glucose in 4 cases, and abnormal liver function in 2 cases. Magnetic resonance imaging showed the disease involved 2 cases of the dorsolateral medulla, 6 cases with bridge arm, 1 case with multiple lesions, and 1 case without abnormal findings. Conclusion: CZV-induced cranial nerve palsy and encephalitis can leave serious sequelae, even life-threatening, early diagnosis and early treatment are essential. For VZV infections confined to the cranial nerve, MRI is necessary even without evidence of brain stem injury, especially DWI sequences and 3D-CISS imaging can show extent of affected early cranial nerve.

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“…HSV-2 genital infection carries a three-fold increased risk for acquisition and transmission of HIV [8]. The common cold sores caused by HSV-1 and the genital herpes lesions caused by HSV-2 are not life-threatening conditions, but serious pathology can result from infections of the cornea (keratitis) or central nervous system (encephalitis), and infection of newborns or immunocompromised individuals can result in severe disseminated disease [9], and Varicella-zoster virus (VZV) or human herpes virus 3 (HHV-3) is 1 of 9 human herpes viruses [10]. VZV is a human pathogen that spreads to children as varicella or chicken pox and reemerges later in life as zoster or shingles [11,12].…”

Section: Introductionmentioning

confidence: 99%

Immunoinformatics Approach-Multiple Peptides Vaccine Design from Glycoprotein E of Herpes Simplex Virus-3

Albagi¹,

Ahmed²,

Mohamme³

et al. 2018

Immunome Res

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Background: Herpes simplex virus (HSV) is a common human pathogen, causing infections of orofacial mucosal surfaces (HSV-1) and genital mucosal surfaces (HSV-2). Productive infection results in the formation of vesicular lesions in the mucosal epithelia, followed by spread of the virus to sensory neurons and establishment of a latent infection that may remain for the life of the host. Material and method: All sequences of glycoprotein E [Human herpes virus 3] were obtained from NCBI and these sequences were subjected to IEDB predicted tools, including B cell and T cell examination, with B cell having multiple tests such as epitopes prediction, surface accessibility and antigenicity prediction; T cell included MHC I and MHC II predicted tools. Finally we used population coverage to select a highest percent of peptides related with different alleles. Result: We obtained some candidate peptides as vaccine derived peptides from B cell test which had a highest score in Emini surface accessibility ("DEDKLDTNSVYEPYYHSDHAESSWVNRGESSRKAYDHNSPYIWPRNDYDGF") of 21.807, and "LKFVDTPESL" with score 1.061 for Kolaskar and Tongaonkar antigenicity test, in another hand we got a highest affinity of peptides that interacted with major coverage of different alleles in MHC I ("KAYDHNSPY") and in MHC II ("MWNYHSHVF"). Conclusion: The efficiency and safety degree in predicted candidate epitopes by computational examination methods are required to be estimated through studies of animal model, to check whether they are able to induce a good defending immune response or not with previous mentioned properties, and we considered this study as first promising peptide based vaccine of [Human herpes virus 3] glycoprotein E in comparison to the previous studies.

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Cellular Stress Response to Varicella-Zoster Virus Infection of Human Skin Includes Highly Elevated Interleukin-6 Expression

Cited by 25 publications

References 42 publications

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

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

Clinical and magnetic resonance analysis of varicella-zoster virus (VZV) transcranial nerve into brain-induced brainstem encephalitis

Immunoinformatics Approach-Multiple Peptides Vaccine Design from Glycoprotein E of Herpes Simplex Virus-3

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