作者
Ryan Schubert,Isobel A. Hawes,Prashanth Ramachandran,Akshaya Ramesh,Emily Crawford,John E. Pak,Wesley Wu,Carly K. Cheung,Brian O’Donovan,Cristina M. Tato,Amy Lyden,Michelle Tan,Rene Sit,Gavin Sowa,Hannah Sample,Kelsey C. Zorn,Debarko Banerji,Lillian M. Khan,Riley Bove,Stephen L. Hauser,Amy A. Gelfand,Bethany L. Johnson-Kerner,Kendall Nash,Kalpathy S. Krishnamoorthy,Tanuja Chitnis,Joy Zhuo Ding,Hugh J. McMillan,Charles Y. Chiu,Benjamin Briggs,Carol Glaser,Cynthia Yen,Victoria Chu,Debra A. Wadford,Samuel R. Dominguez,Terry Fei Fan Ng,Rachel L. Marine,Adriana Lopez,W. Allan Nix,Ariane Soldatos,Mark Gorman,Lina Benson,Kevin Messacar,Jennifer L. Konopka-Anstadt,M. Steven Oberste,Joseph L. DeRisi,Michael R. Wilson
摘要
Since 2012, the United States of America has experienced a biennial spike in pediatric acute flaccid myelitis (AFM)1–6. Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF)2. CSF from children with AFM (n = 42) and other pediatric neurologic disease controls (n = 58) were investigated for intrathecal antiviral antibodies, using a phage display library expressing 481,966 overlapping peptides derived from all known vertebrate and arboviruses (VirScan). Metagenomic next-generation sequencing (mNGS) of AFM CSF RNA (n = 20 cases) was also performed, both unbiased sequencing and with targeted enrichment for EVs. Using VirScan, the viral family significantly enriched by the CSF of AFM cases relative to controls was Picornaviridae, with the most enriched Picornaviridae peptides belonging to the genus Enterovirus (n = 29/42 cases versus 4/58 controls). EV VP1 ELISA confirmed this finding (n = 22/26 cases versus 7/50 controls). mNGS did not detect additional EV RNA. Despite rare detection of EV RNA, pan-viral serology frequently identified high levels of CSF EV-specific antibodies in AFM compared with controls, providing further evidence for a causal role of non-polio EVs in AFM. Antibodies in CSF specific for viral peptides implicate enteroviruses in acute flaccid myelitis.