{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T09:49:32Z","timestamp":1793180972688,"version":"4.5.0"},"reference-count":31,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T00:00:00Z","timestamp":1753833600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003093","name":"Ministry of Higher Education, Malaysia","doi-asserted-by":"publisher","award":["FRGS\/1\/2024\/SKK10\/UM\/02\/19"],"award-info":[{"award-number":["FRGS\/1\/2024\/SKK10\/UM\/02\/19"]}],"id":[{"id":"10.13039\/501100003093","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004386","name":"Universiti Malaya","doi-asserted-by":"publisher","award":["MG029\u20102024"],"award-info":[{"award-number":["MG029\u20102024"]}],"id":[{"id":"10.13039\/501100004386","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Aims<\/jats:title><jats:p>Enterovirus A71 (EV\u2010A71) can cause fatal encephalomyelitis, but the mechanisms of its spread within the central nervous system (CNS) remain unclear. This study aimed to investigate the pathways of EV\u2010A71 dissemination after direct intracerebral inoculation and to assess the role of the murine Scavenger Receptor Class B Member 2 (mSCARB2) receptor in this process.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A mouse\u2010adapted EV\u2010A71 strain (MAVS) was intracerebrally inoculated into the thalamus\/hypothalamus or pons\/medulla of 2\u2010week\u2010old ICR mice. Tissues were harvested and analysed by histopathology and viral titration at 24, 48 and 72\u2009h post\u2010infection (hpi). The infectivity of MAVS was also tested on N1E115 mouse neuroblastoma cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Viral antigens at the injection sites diminished over time, with restricted centrifugal inter\u2010neuronal spread. From 48 hpi, viral antigens increased in distant motor\u2010related neurons of the brainstem and spinal cord. There was a poor correlation between mSCARB2 expression and sites of infection; despite high mSCARB2 expression in the brain, spread was limited, while skeletal muscle, which lacks mSCARB2, showed severe infection. Direct infection of N1E115 cells was inefficient, but viral RNA transfection resulted in robust replication.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The findings suggest a circuitous dissemination route: viral leakage from the CNS leads to viraemia and peripheral muscle infection, followed by retrograde axonal transport back into the brainstem and spinal cord. This pathway appears to be the dominant mode of CNS invasion, independent of mSCARB2 distribution. Alternative receptor pathways likely play a critical role in EV\u2010A71 neuropathogenesis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nan.70031","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T04:44:19Z","timestamp":1753937059000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["An Intracerebrally\u2010Infected Mouse Model of Enterovirus A71 Demonstrates Restricted Inter\u2010Neuronal Spread Within the Brain Parenchyma Despite Strong SCARB2 Expression"],"prefix":"10.1111","volume":"51","author":[{"given":"Munira","family":"Hamidi","sequence":"first","affiliation":[{"name":"Department of Biomedical Science, Faculty of Medicine Universiti Malaya  Kuala Lumpur 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