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Journal article : Review

The immunobiology of herpes simplex virus encephalitis and post-viral autoimmunity

Abstract:
Herpes simplex virus encephalitis (HSE) is the leading cause of non-epidemic encephalitis in the developed world and, despite antiviral therapy, mortality and morbidity is high. The emergence of post-HSE autoimmune encephalitis reveals a new immunological paradigm in autoantibody-mediated disease. A reductionist evaluation of the immunobiological mechanisms in HSE is crucial to dissect the origins of post-viral autoimmunity and supply rational approaches to the selection of immunotherapeutics. Herein, we review the latest evidence behind the phenotypic progression and underlying immunobiology of HSE including the cytokine/chemokine environment, the role of pathogen-recognition receptors, T- and B-cell immunity and relevant inborn errors of immunity. Second, we provide a contemporary review of published patients with post-HSE autoimmune encephalitis from a combined cohort of 110 patients. Third, we integrate novel mechanisms of autoimmunization in deep cervical lymph nodes to explore hypotheses around post-HSE autoimmune encephalitis and challenge these against mechanisms of molecular mimicry and others. Finally, we explore translational concepts where neuroglial surface autoantibodies have been observed with other neuroinfectious diseases and those that generate brain damage including traumatic brain injury, ischaemic stroke and neurodegenerative disease. Overall, the clinical and immunological landscape of HSE is an important and evolving field, from which precision immunotherapeutics could soon emerge.
Publication status:
Published
Peer review status:
Peer reviewed

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Files:
Publisher copy:
10.1093/brain/awad419

Authors


More by this author
Role:
Author
ORCID:
0000-0002-9657-5815
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Institution:
University of Oxford
Division:
MSD
Department:
RDM
Sub department:
RDM Clinical Laboratory Sciences
Role:
Author
ORCID:
0000-0002-6506-2689
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Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
NDM Experimental Medicine
Oxford college:
Green Templeton College
Role:
Author
ORCID:
0000-0003-4307-9161
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Institution:
University of Oxford
Division:
MSD
Department:
Psychiatry
Role:
Author
ORCID:
0000-0002-8242-3722


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Funder identifier:
https://ror.org/029chgv08
Grant:
104079/Z/14/Z
222426/Z/21/Z
More from this funder
Funder identifier:
https://ror.org/03x94j517
Grant:
MR/V007173/1


Publisher:
Oxford University Press
Journal:
Brain More from this journal
Volume:
147
Issue:
4
Pages:
1130-1148
Place of publication:
England
Publication date:
2023-12-13
Acceptance date:
2023-11-27
DOI:
EISSN:
1460-2156
ISSN:
0006-8950
Pmid:
38092513


Language:
English
Keywords:
Subtype:
Review
Pubs id:
1582545
Local pid:
pubs:1582545
Deposit date:
2024-08-08

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