Genomic and serologic characterization of enterovirus A71 brainstem encephalitis.


Journal

Neurology(R) neuroimmunology & neuroinflammation
ISSN: 2332-7812
Titre abrégé: Neurol Neuroimmunol Neuroinflamm
Pays: United States
ID NLM: 101636388

Informations de publication

Date de publication:
05 2020
Historique:
received: 18 10 2019
accepted: 06 02 2020
entrez: 7 3 2020
pubmed: 7 3 2020
medline: 3 8 2021
Statut: epublish

Résumé

In 2016, Catalonia experienced a pediatric brainstem encephalitis outbreak caused by enterovirus A71 (EV-A71). Conventional testing identified EV in the periphery but rarely in CSF. Metagenomic next-generation sequencing (mNGS) and CSF pan-viral serology (VirScan) were deployed to enhance viral detection and characterization. RNA was extracted from the CSF (n = 20), plasma (n = 9), stool (n = 15), and nasopharyngeal samples (n = 16) from 10 children with brainstem encephalitis and 10 children with meningitis or encephalitis. Pathogens were identified using mNGS. Available CSF from cases (n = 12) and pediatric other neurologic disease controls (n = 54) were analyzed with VirScan with a subset (n = 9 and n = 50) validated by ELISA. mNGS detected EV in all samples positive by quantitative reverse transcription polymerase chain reaction (qRT-PCR) (n = 25). In qRT-PCR-negative samples (n = 35), mNGS found virus in 23% (n = 8, 3 CSF samples). Overall, mNGS enhanced EV detection from 42% (25/60) to 57% (33/60) ( mNGS with VirScan significantly increased the CNS detection of EVs relative to qRT-PCR, and the latter generated an antigenic profile of the acute EV-A71 immune response. Genomic analysis confirmed the close relation of the outbreak EV-A71 and neuroinvasive German EV-A71. A S241P substitution in VP1 was found exclusively in the CSF.

Identifiants

pubmed: 32139440
pii: 7/3/e703
doi: 10.1212/NXI.0000000000000703
pmc: PMC7136061
pii:
doi:

Substances chimiques

RNA, Viral 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NINDS NIH HHS
ID : F31 NS113432
Pays : United States
Organisme : NINDS NIH HHS
ID : K08 NS096117
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007618
Pays : United States

Informations de copyright

Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

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Auteurs

Kristoffer E Leon (KE)

From the Medical Scientist Training Program (K.E.L.), University of California, San Francisco; Biomedical Sciences Graduate Program (K.E.L., I.A.H.), University of California, San Francisco; Weill Institute for Neurosciences (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Department of Neurology (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Institut de Recerca Pediàtrica Hospital Sant Joan de Déu (D.C.-A., C.L., A.V.-R., C.M.-A.), Barcelona, Spain; Chan Zuckerberg Biohub (J.E.P., W.W., C.K.C., E.D.C., J.L.D.), San Francisco; Department of Biochemistry and Biophysics (L.M.K., H.A.S., K.C.Z., J.L.D.), University of California, San Francisco; CIBER Epidemiología y Salud Pública (CIBERESP) (C.L., M.C., C.M.-A.), Health Institute Carlos III; Department of Pediatrics (C.L.), Universitat de Barcelona, Barcelona; Enterovirus Unit (M.C.), Spanish National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain; Division of Infectious Diseases (C.L.), Department of Medicine, University of California, San Francisco; and Department of Medicine. Universitat Internacional de Catalunya (C.M.-A.), Barcelona, Spain.

Ryan D Schubert (RD)

From the Medical Scientist Training Program (K.E.L.), University of California, San Francisco; Biomedical Sciences Graduate Program (K.E.L., I.A.H.), University of California, San Francisco; Weill Institute for Neurosciences (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Department of Neurology (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Institut de Recerca Pediàtrica Hospital Sant Joan de Déu (D.C.-A., C.L., A.V.-R., C.M.-A.), Barcelona, Spain; Chan Zuckerberg Biohub (J.E.P., W.W., C.K.C., E.D.C., J.L.D.), San Francisco; Department of Biochemistry and Biophysics (L.M.K., H.A.S., K.C.Z., J.L.D.), University of California, San Francisco; CIBER Epidemiología y Salud Pública (CIBERESP) (C.L., M.C., C.M.-A.), Health Institute Carlos III; Department of Pediatrics (C.L.), Universitat de Barcelona, Barcelona; Enterovirus Unit (M.C.), Spanish National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain; Division of Infectious Diseases (C.L.), Department of Medicine, University of California, San Francisco; and Department of Medicine. Universitat Internacional de Catalunya (C.M.-A.), Barcelona, Spain.

Didac Casas-Alba (D)

From the Medical Scientist Training Program (K.E.L.), University of California, San Francisco; Biomedical Sciences Graduate Program (K.E.L., I.A.H.), University of California, San Francisco; Weill Institute for Neurosciences (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Department of Neurology (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Institut de Recerca Pediàtrica Hospital Sant Joan de Déu (D.C.-A., C.L., A.V.-R., C.M.-A.), Barcelona, Spain; Chan Zuckerberg Biohub (J.E.P., W.W., C.K.C., E.D.C., J.L.D.), San Francisco; Department of Biochemistry and Biophysics (L.M.K., H.A.S., K.C.Z., J.L.D.), University of California, San Francisco; CIBER Epidemiología y Salud Pública (CIBERESP) (C.L., M.C., C.M.-A.), Health Institute Carlos III; Department of Pediatrics (C.L.), Universitat de Barcelona, Barcelona; Enterovirus Unit (M.C.), Spanish National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain; Division of Infectious Diseases (C.L.), Department of Medicine, University of California, San Francisco; and Department of Medicine. Universitat Internacional de Catalunya (C.M.-A.), Barcelona, Spain.

Isobel A Hawes (IA)

From the Medical Scientist Training Program (K.E.L.), University of California, San Francisco; Biomedical Sciences Graduate Program (K.E.L., I.A.H.), University of California, San Francisco; Weill Institute for Neurosciences (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Department of Neurology (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Institut de Recerca Pediàtrica Hospital Sant Joan de Déu (D.C.-A., C.L., A.V.-R., C.M.-A.), Barcelona, Spain; Chan Zuckerberg Biohub (J.E.P., W.W., C.K.C., E.D.C., J.L.D.), San Francisco; Department of Biochemistry and Biophysics (L.M.K., H.A.S., K.C.Z., J.L.D.), University of California, San Francisco; CIBER Epidemiología y Salud Pública (CIBERESP) (C.L., M.C., C.M.-A.), Health Institute Carlos III; Department of Pediatrics (C.L.), Universitat de Barcelona, Barcelona; Enterovirus Unit (M.C.), Spanish National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain; Division of Infectious Diseases (C.L.), Department of Medicine, University of California, San Francisco; and Department of Medicine. Universitat Internacional de Catalunya (C.M.-A.), Barcelona, Spain.

Prashanth S Ramachandran (PS)

From the Medical Scientist Training Program (K.E.L.), University of California, San Francisco; Biomedical Sciences Graduate Program (K.E.L., I.A.H.), University of California, San Francisco; Weill Institute for Neurosciences (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Department of Neurology (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Institut de Recerca Pediàtrica Hospital Sant Joan de Déu (D.C.-A., C.L., A.V.-R., C.M.-A.), Barcelona, Spain; Chan Zuckerberg Biohub (J.E.P., W.W., C.K.C., E.D.C., J.L.D.), San Francisco; Department of Biochemistry and Biophysics (L.M.K., H.A.S., K.C.Z., J.L.D.), University of California, San Francisco; CIBER Epidemiología y Salud Pública (CIBERESP) (C.L., M.C., C.M.-A.), Health Institute Carlos III; Department of Pediatrics (C.L.), Universitat de Barcelona, Barcelona; Enterovirus Unit (M.C.), Spanish National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain; Division of Infectious Diseases (C.L.), Department of Medicine, University of California, San Francisco; and Department of Medicine. Universitat Internacional de Catalunya (C.M.-A.), Barcelona, Spain.

Akshaya Ramesh (A)

From the Medical Scientist Training Program (K.E.L.), University of California, San Francisco; Biomedical Sciences Graduate Program (K.E.L., I.A.H.), University of California, San Francisco; Weill Institute for Neurosciences (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Department of Neurology (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Institut de Recerca Pediàtrica Hospital Sant Joan de Déu (D.C.-A., C.L., A.V.-R., C.M.-A.), Barcelona, Spain; Chan Zuckerberg Biohub (J.E.P., W.W., C.K.C., E.D.C., J.L.D.), San Francisco; Department of Biochemistry and Biophysics (L.M.K., H.A.S., K.C.Z., J.L.D.), University of California, San Francisco; CIBER Epidemiología y Salud Pública (CIBERESP) (C.L., M.C., C.M.-A.), Health Institute Carlos III; Department of Pediatrics (C.L.), Universitat de Barcelona, Barcelona; Enterovirus Unit (M.C.), Spanish National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain; Division of Infectious Diseases (C.L.), Department of Medicine, University of California, San Francisco; and Department of Medicine. Universitat Internacional de Catalunya (C.M.-A.), Barcelona, Spain.

John E Pak (JE)

From the Medical Scientist Training Program (K.E.L.), University of California, San Francisco; Biomedical Sciences Graduate Program (K.E.L., I.A.H.), University of California, San Francisco; Weill Institute for Neurosciences (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Department of Neurology (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Institut de Recerca Pediàtrica Hospital Sant Joan de Déu (D.C.-A., C.L., A.V.-R., C.M.-A.), Barcelona, Spain; Chan Zuckerberg Biohub (J.E.P., W.W., C.K.C., E.D.C., J.L.D.), San Francisco; Department of Biochemistry and Biophysics (L.M.K., H.A.S., K.C.Z., J.L.D.), University of California, San Francisco; CIBER Epidemiología y Salud Pública (CIBERESP) (C.L., M.C., C.M.-A.), Health Institute Carlos III; Department of Pediatrics (C.L.), Universitat de Barcelona, Barcelona; Enterovirus Unit (M.C.), Spanish National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain; Division of Infectious Diseases (C.L.), Department of Medicine, University of California, San Francisco; and Department of Medicine. Universitat Internacional de Catalunya (C.M.-A.), Barcelona, Spain.

Wesley Wu (W)

From the Medical Scientist Training Program (K.E.L.), University of California, San Francisco; Biomedical Sciences Graduate Program (K.E.L., I.A.H.), University of California, San Francisco; Weill Institute for Neurosciences (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Department of Neurology (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Institut de Recerca Pediàtrica Hospital Sant Joan de Déu (D.C.-A., C.L., A.V.-R., C.M.-A.), Barcelona, Spain; Chan Zuckerberg Biohub (J.E.P., W.W., C.K.C., E.D.C., J.L.D.), San Francisco; Department of Biochemistry and Biophysics (L.M.K., H.A.S., K.C.Z., J.L.D.), University of California, San Francisco; CIBER Epidemiología y Salud Pública (CIBERESP) (C.L., M.C., C.M.-A.), Health Institute Carlos III; Department of Pediatrics (C.L.), Universitat de Barcelona, Barcelona; Enterovirus Unit (M.C.), Spanish National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain; Division of Infectious Diseases (C.L.), Department of Medicine, University of California, San Francisco; and Department of Medicine. Universitat Internacional de Catalunya (C.M.-A.), Barcelona, Spain.

Carly K Cheung (CK)

From the Medical Scientist Training Program (K.E.L.), University of California, San Francisco; Biomedical Sciences Graduate Program (K.E.L., I.A.H.), University of California, San Francisco; Weill Institute for Neurosciences (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Department of Neurology (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Institut de Recerca Pediàtrica Hospital Sant Joan de Déu (D.C.-A., C.L., A.V.-R., C.M.-A.), Barcelona, Spain; Chan Zuckerberg Biohub (J.E.P., W.W., C.K.C., E.D.C., J.L.D.), San Francisco; Department of Biochemistry and Biophysics (L.M.K., H.A.S., K.C.Z., J.L.D.), University of California, San Francisco; CIBER Epidemiología y Salud Pública (CIBERESP) (C.L., M.C., C.M.-A.), Health Institute Carlos III; Department of Pediatrics (C.L.), Universitat de Barcelona, Barcelona; Enterovirus Unit (M.C.), Spanish National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain; Division of Infectious Diseases (C.L.), Department of Medicine, University of California, San Francisco; and Department of Medicine. Universitat Internacional de Catalunya (C.M.-A.), Barcelona, Spain.

Emily D Crawford (ED)

From the Medical Scientist Training Program (K.E.L.), University of California, San Francisco; Biomedical Sciences Graduate Program (K.E.L., I.A.H.), University of California, San Francisco; Weill Institute for Neurosciences (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Department of Neurology (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Institut de Recerca Pediàtrica Hospital Sant Joan de Déu (D.C.-A., C.L., A.V.-R., C.M.-A.), Barcelona, Spain; Chan Zuckerberg Biohub (J.E.P., W.W., C.K.C., E.D.C., J.L.D.), San Francisco; Department of Biochemistry and Biophysics (L.M.K., H.A.S., K.C.Z., J.L.D.), University of California, San Francisco; CIBER Epidemiología y Salud Pública (CIBERESP) (C.L., M.C., C.M.-A.), Health Institute Carlos III; Department of Pediatrics (C.L.), Universitat de Barcelona, Barcelona; Enterovirus Unit (M.C.), Spanish National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain; Division of Infectious Diseases (C.L.), Department of Medicine, University of California, San Francisco; and Department of Medicine. Universitat Internacional de Catalunya (C.M.-A.), Barcelona, Spain.

Lillian M Khan (LM)

From the Medical Scientist Training Program (K.E.L.), University of California, San Francisco; Biomedical Sciences Graduate Program (K.E.L., I.A.H.), University of California, San Francisco; Weill Institute for Neurosciences (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Department of Neurology (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Institut de Recerca Pediàtrica Hospital Sant Joan de Déu (D.C.-A., C.L., A.V.-R., C.M.-A.), Barcelona, Spain; Chan Zuckerberg Biohub (J.E.P., W.W., C.K.C., E.D.C., J.L.D.), San Francisco; Department of Biochemistry and Biophysics (L.M.K., H.A.S., K.C.Z., J.L.D.), University of California, San Francisco; CIBER Epidemiología y Salud Pública (CIBERESP) (C.L., M.C., C.M.-A.), Health Institute Carlos III; Department of Pediatrics (C.L.), Universitat de Barcelona, Barcelona; Enterovirus Unit (M.C.), Spanish National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain; Division of Infectious Diseases (C.L.), Department of Medicine, University of California, San Francisco; and Department of Medicine. Universitat Internacional de Catalunya (C.M.-A.), Barcelona, Spain.

Cristian Launes (C)

From the Medical Scientist Training Program (K.E.L.), University of California, San Francisco; Biomedical Sciences Graduate Program (K.E.L., I.A.H.), University of California, San Francisco; Weill Institute for Neurosciences (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Department of Neurology (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Institut de Recerca Pediàtrica Hospital Sant Joan de Déu (D.C.-A., C.L., A.V.-R., C.M.-A.), Barcelona, Spain; Chan Zuckerberg Biohub (J.E.P., W.W., C.K.C., E.D.C., J.L.D.), San Francisco; Department of Biochemistry and Biophysics (L.M.K., H.A.S., K.C.Z., J.L.D.), University of California, San Francisco; CIBER Epidemiología y Salud Pública (CIBERESP) (C.L., M.C., C.M.-A.), Health Institute Carlos III; Department of Pediatrics (C.L.), Universitat de Barcelona, Barcelona; Enterovirus Unit (M.C.), Spanish National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain; Division of Infectious Diseases (C.L.), Department of Medicine, University of California, San Francisco; and Department of Medicine. Universitat Internacional de Catalunya (C.M.-A.), Barcelona, Spain.

Hannah A Sample (HA)

From the Medical Scientist Training Program (K.E.L.), University of California, San Francisco; Biomedical Sciences Graduate Program (K.E.L., I.A.H.), University of California, San Francisco; Weill Institute for Neurosciences (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Department of Neurology (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Institut de Recerca Pediàtrica Hospital Sant Joan de Déu (D.C.-A., C.L., A.V.-R., C.M.-A.), Barcelona, Spain; Chan Zuckerberg Biohub (J.E.P., W.W., C.K.C., E.D.C., J.L.D.), San Francisco; Department of Biochemistry and Biophysics (L.M.K., H.A.S., K.C.Z., J.L.D.), University of California, San Francisco; CIBER Epidemiología y Salud Pública (CIBERESP) (C.L., M.C., C.M.-A.), Health Institute Carlos III; Department of Pediatrics (C.L.), Universitat de Barcelona, Barcelona; Enterovirus Unit (M.C.), Spanish National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain; Division of Infectious Diseases (C.L.), Department of Medicine, University of California, San Francisco; and Department of Medicine. Universitat Internacional de Catalunya (C.M.-A.), Barcelona, Spain.

Kelsey C Zorn (KC)

From the Medical Scientist Training Program (K.E.L.), University of California, San Francisco; Biomedical Sciences Graduate Program (K.E.L., I.A.H.), University of California, San Francisco; Weill Institute for Neurosciences (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Department of Neurology (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Institut de Recerca Pediàtrica Hospital Sant Joan de Déu (D.C.-A., C.L., A.V.-R., C.M.-A.), Barcelona, Spain; Chan Zuckerberg Biohub (J.E.P., W.W., C.K.C., E.D.C., J.L.D.), San Francisco; Department of Biochemistry and Biophysics (L.M.K., H.A.S., K.C.Z., J.L.D.), University of California, San Francisco; CIBER Epidemiología y Salud Pública (CIBERESP) (C.L., M.C., C.M.-A.), Health Institute Carlos III; Department of Pediatrics (C.L.), Universitat de Barcelona, Barcelona; Enterovirus Unit (M.C.), Spanish National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain; Division of Infectious Diseases (C.L.), Department of Medicine, University of California, San Francisco; and Department of Medicine. Universitat Internacional de Catalunya (C.M.-A.), Barcelona, Spain.

Maria Cabrerizo (M)

From the Medical Scientist Training Program (K.E.L.), University of California, San Francisco; Biomedical Sciences Graduate Program (K.E.L., I.A.H.), University of California, San Francisco; Weill Institute for Neurosciences (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Department of Neurology (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Institut de Recerca Pediàtrica Hospital Sant Joan de Déu (D.C.-A., C.L., A.V.-R., C.M.-A.), Barcelona, Spain; Chan Zuckerberg Biohub (J.E.P., W.W., C.K.C., E.D.C., J.L.D.), San Francisco; Department of Biochemistry and Biophysics (L.M.K., H.A.S., K.C.Z., J.L.D.), University of California, San Francisco; CIBER Epidemiología y Salud Pública (CIBERESP) (C.L., M.C., C.M.-A.), Health Institute Carlos III; Department of Pediatrics (C.L.), Universitat de Barcelona, Barcelona; Enterovirus Unit (M.C.), Spanish National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain; Division of Infectious Diseases (C.L.), Department of Medicine, University of California, San Francisco; and Department of Medicine. Universitat Internacional de Catalunya (C.M.-A.), Barcelona, Spain.

Ana Valero-Rello (A)

From the Medical Scientist Training Program (K.E.L.), University of California, San Francisco; Biomedical Sciences Graduate Program (K.E.L., I.A.H.), University of California, San Francisco; Weill Institute for Neurosciences (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Department of Neurology (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Institut de Recerca Pediàtrica Hospital Sant Joan de Déu (D.C.-A., C.L., A.V.-R., C.M.-A.), Barcelona, Spain; Chan Zuckerberg Biohub (J.E.P., W.W., C.K.C., E.D.C., J.L.D.), San Francisco; Department of Biochemistry and Biophysics (L.M.K., H.A.S., K.C.Z., J.L.D.), University of California, San Francisco; CIBER Epidemiología y Salud Pública (CIBERESP) (C.L., M.C., C.M.-A.), Health Institute Carlos III; Department of Pediatrics (C.L.), Universitat de Barcelona, Barcelona; Enterovirus Unit (M.C.), Spanish National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain; Division of Infectious Diseases (C.L.), Department of Medicine, University of California, San Francisco; and Department of Medicine. Universitat Internacional de Catalunya (C.M.-A.), Barcelona, Spain.

Charles Langelier (C)

From the Medical Scientist Training Program (K.E.L.), University of California, San Francisco; Biomedical Sciences Graduate Program (K.E.L., I.A.H.), University of California, San Francisco; Weill Institute for Neurosciences (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Department of Neurology (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Institut de Recerca Pediàtrica Hospital Sant Joan de Déu (D.C.-A., C.L., A.V.-R., C.M.-A.), Barcelona, Spain; Chan Zuckerberg Biohub (J.E.P., W.W., C.K.C., E.D.C., J.L.D.), San Francisco; Department of Biochemistry and Biophysics (L.M.K., H.A.S., K.C.Z., J.L.D.), University of California, San Francisco; CIBER Epidemiología y Salud Pública (CIBERESP) (C.L., M.C., C.M.-A.), Health Institute Carlos III; Department of Pediatrics (C.L.), Universitat de Barcelona, Barcelona; Enterovirus Unit (M.C.), Spanish National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain; Division of Infectious Diseases (C.L.), Department of Medicine, University of California, San Francisco; and Department of Medicine. Universitat Internacional de Catalunya (C.M.-A.), Barcelona, Spain.

Carmen Muñoz-Almagro (C)

From the Medical Scientist Training Program (K.E.L.), University of California, San Francisco; Biomedical Sciences Graduate Program (K.E.L., I.A.H.), University of California, San Francisco; Weill Institute for Neurosciences (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Department of Neurology (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Institut de Recerca Pediàtrica Hospital Sant Joan de Déu (D.C.-A., C.L., A.V.-R., C.M.-A.), Barcelona, Spain; Chan Zuckerberg Biohub (J.E.P., W.W., C.K.C., E.D.C., J.L.D.), San Francisco; Department of Biochemistry and Biophysics (L.M.K., H.A.S., K.C.Z., J.L.D.), University of California, San Francisco; CIBER Epidemiología y Salud Pública (CIBERESP) (C.L., M.C., C.M.-A.), Health Institute Carlos III; Department of Pediatrics (C.L.), Universitat de Barcelona, Barcelona; Enterovirus Unit (M.C.), Spanish National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain; Division of Infectious Diseases (C.L.), Department of Medicine, University of California, San Francisco; and Department of Medicine. Universitat Internacional de Catalunya (C.M.-A.), Barcelona, Spain.

Joseph L DeRisi (JL)

From the Medical Scientist Training Program (K.E.L.), University of California, San Francisco; Biomedical Sciences Graduate Program (K.E.L., I.A.H.), University of California, San Francisco; Weill Institute for Neurosciences (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Department of Neurology (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Institut de Recerca Pediàtrica Hospital Sant Joan de Déu (D.C.-A., C.L., A.V.-R., C.M.-A.), Barcelona, Spain; Chan Zuckerberg Biohub (J.E.P., W.W., C.K.C., E.D.C., J.L.D.), San Francisco; Department of Biochemistry and Biophysics (L.M.K., H.A.S., K.C.Z., J.L.D.), University of California, San Francisco; CIBER Epidemiología y Salud Pública (CIBERESP) (C.L., M.C., C.M.-A.), Health Institute Carlos III; Department of Pediatrics (C.L.), Universitat de Barcelona, Barcelona; Enterovirus Unit (M.C.), Spanish National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain; Division of Infectious Diseases (C.L.), Department of Medicine, University of California, San Francisco; and Department of Medicine. Universitat Internacional de Catalunya (C.M.-A.), Barcelona, Spain.

Michael R Wilson (MR)

From the Medical Scientist Training Program (K.E.L.), University of California, San Francisco; Biomedical Sciences Graduate Program (K.E.L., I.A.H.), University of California, San Francisco; Weill Institute for Neurosciences (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Department of Neurology (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Institut de Recerca Pediàtrica Hospital Sant Joan de Déu (D.C.-A., C.L., A.V.-R., C.M.-A.), Barcelona, Spain; Chan Zuckerberg Biohub (J.E.P., W.W., C.K.C., E.D.C., J.L.D.), San Francisco; Department of Biochemistry and Biophysics (L.M.K., H.A.S., K.C.Z., J.L.D.), University of California, San Francisco; CIBER Epidemiología y Salud Pública (CIBERESP) (C.L., M.C., C.M.-A.), Health Institute Carlos III; Department of Pediatrics (C.L.), Universitat de Barcelona, Barcelona; Enterovirus Unit (M.C.), Spanish National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain; Division of Infectious Diseases (C.L.), Department of Medicine, University of California, San Francisco; and Department of Medicine. Universitat Internacional de Catalunya (C.M.-A.), Barcelona, Spain. michael.wilson@ucsf.edu.

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