دورية أكاديمية
Neural Infection by Oropouche Virus in Adult Human Brain Slices Induces an Inflammatory and Toxic Response.
العنوان: | Neural Infection by Oropouche Virus in Adult Human Brain Slices Induces an Inflammatory and Toxic Response. |
---|---|
المؤلفون: | Almeida GM; Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.; Center for Virus Research, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Souza JP; Center for Virus Research, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.; Department of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Mendes ND; Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.; Department of Pathology and Forensic Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Pontelli MC; Center for Virus Research, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.; Department of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Pinheiro NR; Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Nogueira GO; Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Cardoso RS; Center for Virus Research, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.; Department of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Paiva IM; Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.; Center for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Ferrari GD; Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil., Veras FP; Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.; Center for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Cunha FQ; Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.; Center for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Horta-Junior JAC; Department of Structural and Functional Biology (Anatomy), Institute of Biosciences, São Paulo State University, Botucatu, Brazil., Alberici LC; Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil., Cunha TM; Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.; Center for Research in Inflammatory Diseases (CRID), Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Podolsky-Gondim GG; Division of Neurosurgery, Department of Surgery and Anatomy, Ribeirão Preto Clinics Hospital, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Neder L; Department of Pathology and Forensic Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Arruda E; Center for Virus Research, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.; Department of Cell and Molecular Biology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Sebollela A; Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil. |
المصدر: | Frontiers in neuroscience [Front Neurosci] 2021 Nov 23; Vol. 15, pp. 674576. Date of Electronic Publication: 2021 Nov 23 (Print Publication: 2021). |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Frontiers Research Foundation Country of Publication: Switzerland NLM ID: 101478481 Publication Model: eCollection Cited Medium: Print ISSN: 1662-4548 (Print) Linking ISSN: 1662453X NLM ISO Abbreviation: Front Neurosci Subsets: PubMed not MEDLINE |
أسماء مطبوعة: | Original Publication: Lausanne : Frontiers Research Foundation |
مستخلص: | Oropouche virus (OROV) is an emerging arbovirus in South and Central Americas with high spreading potential. OROV infection has been associated with neurological complications and OROV genomic RNA has been detected in cerebrospinal fluid from patients, suggesting its neuroinvasive potential. Motivated by these findings, neurotropism and neuropathogenesis of OROV have been investigated in vivo in murine models, which do not fully recapitulate the complexity of the human brain. Here we have used slice cultures from adult human brains to investigate whether OROV is capable of infecting mature human neural cells in a context of preserved neural connections and brain cytoarchitecture. Our results demonstrate that human neural cells can be infected ex vivo by OROV and support the production of infectious viral particles. Moreover, OROV infection led to the release of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) and diminished cell viability 48 h post-infection, indicating that OROV triggers an inflammatory response and tissue damage. Although OROV-positive neurons were observed, microglia were the most abundant central nervous system (CNS) cell type infected by OROV, suggesting that they play an important role in the response to CNS infection by OROV in the adult human brain. Importantly, we found no OROV-infected astrocytes. To the best of our knowledge, this is the first direct demonstration of OROV infection in human brain cells. Combined with previous data from murine models and case reports of OROV genome detection in cerebrospinal fluid from patients, our data shed light on OROV neuropathogenesis and help raising awareness about acute and possibly chronic consequences of OROV infection in the human brain. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Almeida, Souza, Mendes, Pontelli, Pinheiro, Nogueira, Cardoso, Paiva, Ferrari, Veras, Cunha, Horta-Junior, Alberici, Cunha, Podolsky-Gondim, Neder, Arruda and Sebollela.) |
References: | Neurotherapeutics. 2016 Jul;13(3):493-508. (PMID: 27106239) Cell Stem Cell. 2020 Dec 3;27(6):937-950.e9. (PMID: 33010822) Ann Transl Med. 2015 Jun;3(10):136. (PMID: 26207229) Int J Infect Dis. 2019 Jun;83:139-144. (PMID: 30991139) Proc Natl Acad Sci U S A. 2010 Jul 13;107(28):12698-703. (PMID: 20616000) Front Cell Infect Microbiol. 2019 Oct 24;9:362. (PMID: 31709195) Proc Natl Acad Sci U S A. 2016 Dec 13;113(50):14408-14413. (PMID: 27911847) Viruses. 2018 Apr 04;10(4):. (PMID: 29617280) Neurosci Lett. 2017 Apr 3;645:106-112. (PMID: 28259657) J Med Virol. 2017 Jun;89(6):1108-1111. (PMID: 27787907) J Virol. 2017 Oct 27;91(22):. (PMID: 28878079) Science. 2016 May 13;352(6287):816-8. (PMID: 27064148) Viruses. 2021 Jan 19;13(1):. (PMID: 33477869) Neurology. 2015 Jan 27;84(4):421-3. (PMID: 25628429) Am J Trop Med Hyg. 2012 Apr;86(4):732-5. (PMID: 22492162) Nature. 2019 Sep;573(7772):61-68. (PMID: 31435019) Mol Psychiatry. 2020 Feb;25(2):351-367. (PMID: 31772305) Neurosci Bull. 2019 Apr;35(2):244-252. (PMID: 30604279) Sci Rep. 2016 Apr 21;6:24818. (PMID: 27098488) Emerg Infect Dis. 2019 Feb;25(2):380-382. (PMID: 30666950) J Neurosci Methods. 2016 Feb 15;260:221-32. (PMID: 26434706) Virus Res. 2012 Dec;170(1-2):25-33. (PMID: 22877689) Proc Natl Acad Sci U S A. 2008 Nov 4;105(44):17151-6. (PMID: 18955701) Cureus. 2020 Aug 11;12(8):e9674. (PMID: 32923269) J Virol. 2015 Oct 14;90(1):189-205. (PMID: 26468541) Am J Trop Med Hyg. 2017 May;96(5):1019-1030. (PMID: 28167595) J Neuroinflammation. 2019 Apr 9;16(1):76. (PMID: 30967139) Clin Infect Dis. 2007 Jun 15;44(12):1617-24. (PMID: 17516407) Brain Behav Immun Health. 2020 Jul 18;7:100105. (PMID: 34589866) PLoS Pathog. 2018 Jan 19;14(1):e1006845. (PMID: 29352299) Front Synaptic Neurosci. 2018 Jun 08;10:15. (PMID: 29937727) J Exp Med. 2021 Mar 1;218(3):. (PMID: 33433624) Front Neurol. 2018 Mar 27;9:111. (PMID: 29636722) J Neuroimmunol. 2017 Aug 15;309:12-22. (PMID: 28601280) Cell Mol Immunol. 2021 Feb;18(2):250-258. (PMID: 33437050) Sci Rep. 2020 Sep 16;10(1):15209. (PMID: 32938988) Mult Scler. 2006 Oct;12(5):558-64. (PMID: 17086900) Virus Res. 2010 Apr;149(1):56-63. (PMID: 20080135) J Neurosci Methods. 2011 Aug 30;200(1):74-9. (PMID: 21726582) N Engl J Med. 2018 Aug 9;379(6):557-566. (PMID: 30089069) Nat Methods. 2012 Jun 28;9(7):676-82. (PMID: 22743772) Rev Inst Med Trop Sao Paulo. 1982 Jul-Aug;24(4):246-51. (PMID: 6818668) Microbes Infect. 2018 Mar;20(3):135-146. (PMID: 29247710) Neurosci Lett. 2019 Mar 23;696:219-224. (PMID: 30610890) J Virol. 2014 Nov;88(22):13005-14. (PMID: 25165111) Alzheimers Res Ther. 2015 Aug 19;7(1):56. (PMID: 26286145) Front Cell Neurosci. 2019 Oct 25;13:472. (PMID: 31708746) Virology. 2018 Mar;516:46-54. (PMID: 29329078) Viruses. 2014 Oct 10;6(10):3827-36. (PMID: 25310583) J Vis Exp. 2019 Nov 5;(153):. (PMID: 31762466) J Virol. 2014 Jan;88(2):1080-9. (PMID: 24198425) Epilepsy Res Treat. 2012;2012:624519. (PMID: 22957233) Nat Commun. 2019 Sep 5;10(1):3890. (PMID: 31488835) Cell Host Microbe. 2013 Apr 17;13(4):379-93. (PMID: 23601101) Annu Rev Immunol. 2019 Apr 26;37:73-95. (PMID: 31026414) J Alzheimers Dis. 2013;33 Suppl 1:S123-39. (PMID: 22710920) J Physiol. 2017 Mar 15;595(6):1929-1945. (PMID: 27104646) Acta Neuropathol. 2018 Sep;136(3):461-482. (PMID: 30027450) Mol Neurobiol. 2019 Sep;56(9):6409-6425. (PMID: 30805836) Acta Neuropathol. 2016 Feb;131(2):159-184. (PMID: 26659576) J Biol Chem. 2012 Mar 2;287(10):7436-45. (PMID: 22235132) J Neurosci Methods. 2018 Sep 1;307:203-209. (PMID: 29859877) Viruses. 2020 Jul 21;12(7):. (PMID: 32708342) Clin Dev Immunol. 2013;2013:510396. (PMID: 23864878) ACS Chem Neurosci. 2018 Aug 15;9(8):1975-1985. (PMID: 29847093) J Virol. 1987 Jul;61(7):2319-21. (PMID: 3586135) PLoS Pathog. 2018 May 3;14(5):e1007047. (PMID: 29723305) Virus Res. 2011 Jan;155(1):35-41. (PMID: 20727376) J Neurosci Methods. 2018 Mar 15;298:33-44. (PMID: 29427611) BMC Infect Dis. 2015 Aug 19;15:345. (PMID: 26286516) J Virol. 2004 Oct;78(20):11429-33. (PMID: 15452268) J Virol. 2005 Apr;79(7):4369-81. (PMID: 15767437) Sci Rep. 2018 May 30;8(1):8407. (PMID: 29849137) Nat Immunol. 2020 Nov;21(11):1327-1335. (PMID: 32839612) |
فهرسة مساهمة: | Keywords: arboviruses; histocultures; human brain; neuroinfection; neuroinflammation; neurotropic virus; viral encephalitis |
تواريخ الأحداث: | Date Created: 20211210 Latest Revision: 20230921 |
رمز التحديث: | 20230921 |
مُعرف محوري في PubMed: | PMC8651276 |
DOI: | 10.3389/fnins.2021.674576 |
PMID: | 34887719 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1662-4548 |
---|---|
DOI: | 10.3389/fnins.2021.674576 |