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Lack of Major Histocompatibility Complex Class I Upregulation and Restrictive Infection by JC Virus Hamper Detection of Neurons by T Lymphocytes in the Central Nervous System
Open accessAbstract
The human polyomavirus JC (JCV) infects glial cells in immunosuppressed individuals, leading to progressive multifocal leukoencephalopathy. Polyomavirus JC can also infect neurons in patients with JCV granule cell neuronopathy and JCV encephalopathy. CD8-positive T cells play a crucial role in viral containment and outcome in progressive multifocal leukoencephalopathy, but whether CD8-positive T cells can also recognize JCV-infected neurons is unclear. We used immunohistochemistry to determine the prevalence of T cells in neuron-rich areas of archival brain samples from 77 patients with JCV CNS infections and 94 control subjects. Neurons predominantly sustained a restrictive infection with expression of JCV regulatory protein T antigen (T Ag), whereas glial cells were productively infected and expressed both T Ag and the capsid protein VP1. T cells were more prevalent near JCV-infected cells with intact nuclei expressing both T Ag and VP1 compared with those expressing either protein alone. CD8-positive T cells also colocalized more with JCV-infected glial cells than with JCV-infected neurons. Major histocompatibility complex class I expression was upregulated in JCV-infected areas but could only be detected in rare neurons interspersed with infected glial cells. These results suggest that isolated neurons harboring restrictive JCV infection do not upregulate major histocompatibility complex class I and thus may escape recognition by CD8-positive T cells.
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“Due to the lack of major histocompatibility complex antigens in nerve cells, the elimination of viruses in nerve cells depends solely on the role of cytotoxic T cells; however, the apoptosis of mature neurons after virus infection also has a relatively protective effect (Wuthrich et al., 2015).”
From Nervous system involvement after infection with COVID-19 and other coronaviruses (2020) · cites this paper as Wuthrich et al., 2015
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“however, the apoptosis of mature neurons after virus infection also has a relatively protective effect (Wuthrich et al., 2015).”
From Nervous system involvement after infection with COVID-19 and other coronaviruses (2020) · cites this paper as Wuthrich et al., 2015
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Metadata
- Authors
- Wüthrich, C., Batson, S., & Koralnik, I. J.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Koralnik, Igor J.
- ORCID
- Koralnik, Igor J.
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-08
- Volume
- 74
- Issue
- 8
- Pages
- 791-803
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- PMC
- PMC4506730
- OpenAlex
- W1030692554
- Cited by
- 10
- References
- 58
- Citations by year
- 2025: 1 · 2021: 2 · 2020: 6 · 2018: 1
- FWCI
- 0.15
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (U24MH100928, U01MH083500, U24MH100929)
- National Institute of Neurological Disorders and Stroke (R01NS074995, NS 074995, NS 047029, R01NS047029)
- Topics
- Health Sciences › Medicine › Oncology › Polyomavirus and related diseases
- Health Sciences › Medicine › Infectious Diseases › Viral Infections and Immunology Research
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Keywords
- JC virus, polyomavirus, MHC class I upregulation, CD8+ T cells, progressive multifocal leukoencephalopathy, T antigen, VP1 capsid protein, T cell escape, viral infections of the central nervous system
- MeSH terms
- Brain, Female, Fluorescent Antibody Technique, Humans, JC Virus, Male, Middle Aged, Neurons, Histocompatibility Antigens Class I, Up-Regulation, CD8-Positive T-Lymphocytes, Polyomavirus Infections
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