Spatiotemporal profile of an optimal host response to virus infection in the primate central nervous system.
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| Název: | Spatiotemporal profile of an optimal host response to virus infection in the primate central nervous system. |
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| Autoři: | Maximova OA; Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, Maryland, United States of America., Anzick SL; Rocky Mountain Laboratories, Research Technologies Branch, Genomics Research Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Hamilton, Montana, United States of America., Sturdevant DE; Rocky Mountain Laboratories, Research Technologies Branch, Genomics Research Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Hamilton, Montana, United States of America., Bennett RS; Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, Maryland, United States of America., Faucette LJ; Infectious Disease Pathogenesis Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, Maryland, United States of America., St Claire M; Bioqual, Inc., Rockville, Maryland, United States of America., Whitehead SS; Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, Maryland, United States of America., Kanakabandi K; Rocky Mountain Laboratories, Research Technologies Branch, Genomics Research Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Hamilton, Montana, United States of America., Sheng ZM; Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, Maryland, United States of America., Xiao Y; Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, Maryland, United States of America., Kash JC; Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, Maryland, United States of America., Taubenberger JK; Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, Maryland, United States of America., Martens C; Rocky Mountain Laboratories, Research Technologies Branch, Genomics Research Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Hamilton, Montana, United States of America., Cohen JI; Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, Maryland, United States of America. |
| Zdroj: | PLoS pathogens [PLoS Pathog] 2025 Jan 22; Vol. 21 (1), pp. e1012530. Date of Electronic Publication: 2025 Jan 22 (Print Publication: 2025). |
| Způsob vydávání: | Journal Article |
| Jazyk: | English |
| Informace o časopise: | Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: San Francisco, CA : Public Library of Science, c2005- |
| Výrazy ze slovníku MeSH: | La Crosse virus*/immunology , Central Nervous System*/virology , Central Nervous System*/immunology , Encephalitis, California*/immunology , Encephalitis, California*/virology , Encephalitis, California*/pathology, Animals ; Virus Replication ; Neurons/virology ; Macaca mulatta |
| Abstrakt: | Competing Interests: The authors have declared that no competing interests exist. Viral infections of the central nervous system (CNS) are a major cause of morbidity largely due to lack of prevention and inadequate treatments. While mortality from viral CNS infections is significant, nearly two thirds of the patients survive. Thus, it is important to understand how the human CNS can successfully control virus infection and recover. Since it is not possible to study the human CNS throughout the course of viral infection at the cellular level, here we analyzed a non-lethal viral infection in the CNS of nonhuman primates (NHPs). We inoculated NHPs intracerebrally with a high dose of La Crosse virus (LACV), a bunyavirus that can infect neurons and cause encephalitis primarily in children, but with a very low (≤ 1%) mortality rate. To profile the CNS response to LACV infection, we used an integrative approach that was based on comprehensive analyses of (i) spatiotemporal dynamics of virus replication, (ii) identification of types of infected neurons, (iii) spatiotemporal transcriptomics, and (iv) morphological and functional changes in CNS intrinsic and extrinsic cells. We identified the location, timing, and functional repertoire of optimal transcriptional and translational regulation of the primate CNS in response to virus infection of neurons. These CNS responses involved a well-coordinated spatiotemporal interplay between astrocytes, lymphocytes, microglia, and CNS-border macrophages. Our findings suggest a multifaceted program governing an optimal CNS response to virus infection with specific events coordinated in space and time. This allowed the CNS to successfully control the infection by rapidly clearing the virus from infected neurons, mitigate damage to neurophysiology, activate and terminate immune responses in a timely manner, resolve inflammation, restore homeostasis, and initiate tissue repair. An increased understanding of these processes may provide new therapeutic opportunities to improve outcomes of viral CNS diseases in humans. (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.) |
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| Entry Date(s): | Date Created: 20250122 Date Completed: 20250503 Latest Revision: 20250503 |
| Update Code: | 20250503 |
| PubMed Central ID: | PMC11753669 |
| DOI: | 10.1371/journal.ppat.1012530 |
| PMID: | 39841753 |
| Databáze: | MEDLINE |
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Nájsť tento článok vo Web of Science | Abstrakt: | Competing Interests: The authors have declared that no competing interests exist.<br />Viral infections of the central nervous system (CNS) are a major cause of morbidity largely due to lack of prevention and inadequate treatments. While mortality from viral CNS infections is significant, nearly two thirds of the patients survive. Thus, it is important to understand how the human CNS can successfully control virus infection and recover. Since it is not possible to study the human CNS throughout the course of viral infection at the cellular level, here we analyzed a non-lethal viral infection in the CNS of nonhuman primates (NHPs). We inoculated NHPs intracerebrally with a high dose of La Crosse virus (LACV), a bunyavirus that can infect neurons and cause encephalitis primarily in children, but with a very low (≤ 1%) mortality rate. To profile the CNS response to LACV infection, we used an integrative approach that was based on comprehensive analyses of (i) spatiotemporal dynamics of virus replication, (ii) identification of types of infected neurons, (iii) spatiotemporal transcriptomics, and (iv) morphological and functional changes in CNS intrinsic and extrinsic cells. We identified the location, timing, and functional repertoire of optimal transcriptional and translational regulation of the primate CNS in response to virus infection of neurons. These CNS responses involved a well-coordinated spatiotemporal interplay between astrocytes, lymphocytes, microglia, and CNS-border macrophages. Our findings suggest a multifaceted program governing an optimal CNS response to virus infection with specific events coordinated in space and time. This allowed the CNS to successfully control the infection by rapidly clearing the virus from infected neurons, mitigate damage to neurophysiology, activate and terminate immune responses in a timely manner, resolve inflammation, restore homeostasis, and initiate tissue repair. An increased understanding of these processes may provide new therapeutic opportunities to improve outcomes of viral CNS diseases in humans.<br /> (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.) |
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| ISSN: | 1553-7374 |
| DOI: | 10.1371/journal.ppat.1012530 |