{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T23:11:08Z","timestamp":1771456268863,"version":"3.50.1"},"reference-count":74,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2018,3,15]],"date-time":"2018-03-15T00:00:00Z","timestamp":1521072000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100003093","name":"Ministry of Higher Education, Malaysia","doi-asserted-by":"publisher","award":["H20001-E00004"],"award-info":[{"award-number":["H20001-E00004"]}],"id":[{"id":"10.13039\/501100003093","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003093","name":"Ministry of Higher Education, Malaysia","doi-asserted-by":"publisher","award":["FP019\/2016)."],"award-info":[{"award-number":["FP019\/2016)."]}],"id":[{"id":"10.13039\/501100003093","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2018,3,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Coxsackievirus A16 (CV-A16) and enterovirus A71 (EV-A71) are closely related enteroviruses that cause the same hand, foot, and mouth disease (HFMD), but neurological complications occur only very rarely in CV-A16 compared to EV-A71 infections. To elucidate host responses that may be able to explain these differences, we performed transcriptomic analysis and real-time quantitative PCR (RT-qPCR) in CV-A16-infected neuroblastoma cells (SK-N-SH), and the results showed that the radical\n            <jats:italic>S<\/jats:italic>\n            -adenosylmethionine domain containing 2 (RSAD2) was the highest upregulated gene in the antimicrobial pathway. Increased RSAD2 expression was correlated with reduced viral replication, while RSAD2 knockdown cells were correlated with increased replication. EV-A71 replication showed no apparent correlation to RSAD2 expressions. Absent in melanoma 2 (AIM2), which is associated with pyroptotic cell death, was upregulated in EV-A71-infected neurons but not in CV-A16 infection, suggesting that the AIM2 inflammasome played a significant role in suppressing EV-A71 replication. Chimeric viruses derived from CV-A16 and EV-A71 but containing swapped 5\u2032 nontranslated regions (5\u2032 NTRs) showed that RSAD2 expression\/viral replication and AIM2 expression\/viral replication patterns may be linked to the 5\u2032 NTRs of parental viruses. Differences in secondary structure of internal ribosomal entry sites within the 5\u2032 NTR may be responsible for these findings. Overall, our results suggest that CV-A16 and EV-A71 elicit different host responses to infection, which may help explain the apparent lower incidence of CV-A16-associated neurovirulence in HFMD outbreaks compared to EV-A71 infection.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Although coxsackievirus A16 (CV-A16) and enterovirus A17 (EV-A71) both cause hand, foot, and mouth disease, EV-A71 has emerged as a leading cause of nonpolio, enteroviral fatal encephalomyelitis among young children. The significance of our research is in the identification of the possible differing and novel mechanisms of CV-A16 and EV-A71 inhibition in neuronal cells that may impact viral neuropathogenesis. We further showed that viral 5\u2032 NTRs may play significant roles in eliciting different host response mechanisms.\n          <\/jats:p>","DOI":"10.1128\/jvi.01914-17","type":"journal-article","created":{"date-parts":[[2017,12,21]],"date-time":"2017-12-21T13:16:06Z","timestamp":1513862166000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":22,"title":["RSAD2 and AIM2 Modulate Coxsackievirus A16 and Enterovirus A71 Replication in Neuronal Cells in Different Ways That May Be Associated with Their 5\u2032 Nontranslated Regions"],"prefix":"10.1128","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6894-1478","authenticated-orcid":false,"given":"Thinesshwary","family":"Yogarajah","sequence":"first","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kien Chai","family":"Ong","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Perera","sequence":"additional","affiliation":[{"name":"Institute of Health and Community Medicine, Universiti Malaysia Sarawak, Sarawak, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kum Thong","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02476-08"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/v7082832"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1008.040059"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-11-246"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM196305092681904"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.inf.0000115950.63906.78"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1510.090594"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00705-016-3157-4"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2015.05.016"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00902-12"},{"key":"e_1_3_2_12_2","first-page":"343","article-title":"Pathological findings in a mouse model for coxsackievirus A16 infection","volume":"20","author":"Hooi YT","year":"2015","unstructured":"Hooi YT, Ong KC, Perera D, Wong KT. 2015. 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