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Genetic Variants an...
Genetic Variants and Immune Responses in a Cohort of Patients With Varicella Zoster Virus Encephalitis
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Thomsen, M. M. (author)
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- Tyrberg, Tobias (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine
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Skaalum, K. (author)
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Carter-Timofte, M. (author)
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Freytag, M. R. (author)
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- Norberg, Peter, 1974 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine
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Helleberg, M. (author)
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Storgaard, M. (author)
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Nielsen, H. (author)
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Bodilsen, J. (author)
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- Grahn, Anna, 1973 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine
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Mogensen, T. H. (author)
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(creator_code:org_t)
- 2021-05-11
- 2021
- English.
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In: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 224:12, s. 2122-2132
- Related links:
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
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- Background. Infection with varicella zoster virus (VZV) may involve different central nervous system (CNS) manifestations, including meningitis, encephalitis, and vasculitis. In cases in which otherwise healthy individuals are affected, an inborn error of immunity may underlie increased susceptibility or severity of infection. Methods. We collected a cohort of 17 adults who experienced VZV encephalitis and performed whole exome sequencing. Patient peripheral blood mononuclear cells were infected with VZV, and innate antiviral interferon (IFN) and cytokine responses as well as viral replication were evaluated. Data were analyzed by Mann-Whitney U test. Results. We identified a total of 21 different potentially disease-causing variants in a total of 13 of the 17 patients included. These gene variants were within 2 major functional clusters: (1) innate viral sensors and immune pathways and (2) autophagy pathways. Antiviral IFN and cytokine responses were abnormal in the majority of patients, whereas viral replication was increased in only 2 of 17 patients. Conclusions. This study identifies a list of variants of pathogenic potential, which may serve as a platform for generating hypotheses for future studies addressing genetic and immunological factors associated with susceptibility to VZV encephalitis. These data, taken together, suggest that disturbances in innate sensing and autophagy pathways may predispose to VZV encephalitis.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
Keyword
- autophagy
- inborn error of immunity
- interferon
- varicella zoster virus
- whole exome sequencing
- viral-infections
- nervous-system
- inborn-errors
- deficiency
- autophagy
- oligomerization
- mycobacterial
- mechanisms
- induction
- proteins
- Immunology
- Infectious Diseases
- Microbiology
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Thomsen, M. M.
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Tyrberg, Tobias
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Skaalum, K.
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Carter-Timofte, ...
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Freytag, M. R.
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Norberg, Peter, ...
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show more...
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Helleberg, M.
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Storgaard, M.
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Nielsen, H.
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Bodilsen, J.
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Grahn, Anna, 197 ...
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Mogensen, T. H.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Infectious Medic ...
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Journal of Infec ...
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University of Gothenburg