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Polyomavirus Wakes Up and Chooses Neurovirulence

JC polyomavirus (JCPyV) is a human-specific polyomavirus that establishes a silent lifelong infection in multiple peripheral organs, predominantly those of the urinary tract, of immunocompetent individuals. In immunocompromised settings, however, JCPyV can infiltrate the central nervous system (CNS)...

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Autores principales: Butic, Arrienne B., Spencer, Samantha A., Shaheen, Shareef K., Lukacher, Aron E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10612099/
https://www.ncbi.nlm.nih.gov/pubmed/37896889
http://dx.doi.org/10.3390/v15102112
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author Butic, Arrienne B.
Spencer, Samantha A.
Shaheen, Shareef K.
Lukacher, Aron E.
author_facet Butic, Arrienne B.
Spencer, Samantha A.
Shaheen, Shareef K.
Lukacher, Aron E.
author_sort Butic, Arrienne B.
collection PubMed
description JC polyomavirus (JCPyV) is a human-specific polyomavirus that establishes a silent lifelong infection in multiple peripheral organs, predominantly those of the urinary tract, of immunocompetent individuals. In immunocompromised settings, however, JCPyV can infiltrate the central nervous system (CNS), where it causes several encephalopathies of high morbidity and mortality. JCPyV-induced progressive multifocal leukoencephalopathy (PML), a devastating demyelinating brain disease, was an AIDS-defining illness before antiretroviral therapy that has “reemerged” as a complication of immunomodulating and chemotherapeutic agents. No effective anti-polyomavirus therapeutics are currently available. How depressed immune status sets the stage for JCPyV resurgence in the urinary tract, how the virus evades pre-existing antiviral antibodies to become viremic, and where/how it enters the CNS are incompletely understood. Addressing these questions requires a tractable animal model of JCPyV CNS infection. Although no animal model can replicate all aspects of any human disease, mouse polyomavirus (MuPyV) in mice and JCPyV in humans share key features of peripheral and CNS infection and antiviral immunity. In this review, we discuss the evidence suggesting how JCPyV migrates from the periphery to the CNS, innate and adaptive immune responses to polyomavirus infection, and how the MuPyV-mouse model provides insights into the pathogenesis of JCPyV CNS disease.
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spelling pubmed-106120992023-10-29 Polyomavirus Wakes Up and Chooses Neurovirulence Butic, Arrienne B. Spencer, Samantha A. Shaheen, Shareef K. Lukacher, Aron E. Viruses Review JC polyomavirus (JCPyV) is a human-specific polyomavirus that establishes a silent lifelong infection in multiple peripheral organs, predominantly those of the urinary tract, of immunocompetent individuals. In immunocompromised settings, however, JCPyV can infiltrate the central nervous system (CNS), where it causes several encephalopathies of high morbidity and mortality. JCPyV-induced progressive multifocal leukoencephalopathy (PML), a devastating demyelinating brain disease, was an AIDS-defining illness before antiretroviral therapy that has “reemerged” as a complication of immunomodulating and chemotherapeutic agents. No effective anti-polyomavirus therapeutics are currently available. How depressed immune status sets the stage for JCPyV resurgence in the urinary tract, how the virus evades pre-existing antiviral antibodies to become viremic, and where/how it enters the CNS are incompletely understood. Addressing these questions requires a tractable animal model of JCPyV CNS infection. Although no animal model can replicate all aspects of any human disease, mouse polyomavirus (MuPyV) in mice and JCPyV in humans share key features of peripheral and CNS infection and antiviral immunity. In this review, we discuss the evidence suggesting how JCPyV migrates from the periphery to the CNS, innate and adaptive immune responses to polyomavirus infection, and how the MuPyV-mouse model provides insights into the pathogenesis of JCPyV CNS disease. MDPI 2023-10-18 /pmc/articles/PMC10612099/ /pubmed/37896889 http://dx.doi.org/10.3390/v15102112 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Butic, Arrienne B.
Spencer, Samantha A.
Shaheen, Shareef K.
Lukacher, Aron E.
Polyomavirus Wakes Up and Chooses Neurovirulence
title Polyomavirus Wakes Up and Chooses Neurovirulence
title_full Polyomavirus Wakes Up and Chooses Neurovirulence
title_fullStr Polyomavirus Wakes Up and Chooses Neurovirulence
title_full_unstemmed Polyomavirus Wakes Up and Chooses Neurovirulence
title_short Polyomavirus Wakes Up and Chooses Neurovirulence
title_sort polyomavirus wakes up and chooses neurovirulence
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10612099/
https://www.ncbi.nlm.nih.gov/pubmed/37896889
http://dx.doi.org/10.3390/v15102112
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