{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:51:05Z","timestamp":1782175865195,"version":"3.54.5"},"reference-count":97,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T00:00:00Z","timestamp":1631577600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R15AI144686"],"award-info":[{"award-number":["R15AI144686"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P20GM103423"],"award-info":[{"award-number":["P20GM103423"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"College of NSFA, University of Maine","award":["Biomedical Sciences Accelerator Fund Faculty Award"],"award-info":[{"award-number":["Biomedical Sciences Accelerator Fund Faculty Award"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>JC polyomavirus (JCPyV) is a neuroinvasive pathogen causing a fatal, demyelinating disease of the central nervous system (CNS) known as progressive multifocal leukoencephalopathy (PML). Within the CNS, JCPyV predominately targets two cell types: oligodendrocytes and astrocytes. The underlying mechanisms of astrocytic infection are poorly understood, yet recent findings suggest critical differences in JCPyV infection of primary astrocytes compared to a widely studied immortalized cell model. RNA sequencing was performed in primary normal human astrocytes (NHAs) to analyze the transcriptomic profile that emerges during JCPyV infection. Through a comparative analysis, it was validated that JCPyV requires the mitogen-activated protein kinase, extracellular signal-regulated kinase (MAPK\/ERK) pathway, and additionally requires the expression of dual-specificity phosphatases (DUSPs). Specifically, the expression of DUSP1 is needed to establish a successful infection in NHAs, yet this was not observed in an immortalized cell model of JCPyV infection. Additional analyses demonstrated immune activation uniquely observed in NHAs. These results support the hypothesis that DUSPs within the MAPK\/ERK pathway impact viral infection and influence potential downstream targets and cellular pathways. Collectively, this research implicates DUSP1 in JCPyV infection of primary human astrocytes, and most importantly, further resolves the signaling events that lead to successful JCPyV infection in the CNS.<\/jats:p>","DOI":"10.3390\/v13091834","type":"journal-article","created":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T23:34:11Z","timestamp":1631662451000},"page":"1834","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["The MAPK\/ERK Pathway and the Role of DUSP1 in JCPyV Infection of Primary Astrocytes"],"prefix":"10.3390","volume":"13","author":[{"given":"Michael P.","family":"Wilczek","sequence":"first","affiliation":[{"name":"Department of Molecular and Biomedical Sciences, University of Maine, Orono, ME 04469, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca J.","family":"Armstrong","sequence":"additional","affiliation":[{"name":"Department of Molecular and Biomedical Sciences, University of Maine, Orono, ME 04469, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Remi P.","family":"Geohegan","sequence":"additional","affiliation":[{"name":"Department of Molecular and Biomedical Sciences, University of Maine, Orono, ME 04469, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colleen L.","family":"Mayberry","sequence":"additional","affiliation":[{"name":"Department of Molecular and Biomedical Sciences, University of Maine, Orono, ME 04469, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanne K.","family":"DuShane","sequence":"additional","affiliation":[{"name":"Department of Molecular and Biomedical Sciences, University of Maine, Orono, ME 04469, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin L.","family":"King","sequence":"additional","affiliation":[{"name":"Department of Molecular and Biomedical Sciences, University of Maine, Orono, ME 04469, USA"},{"name":"Graduate School in Biomedical Sciences and Engineering, University of Maine, Orono, ME 04469, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa S.","family":"Maginnis","sequence":"additional","affiliation":[{"name":"Department of Molecular and Biomedical Sciences, University of Maine, Orono, ME 04469, USA"},{"name":"Graduate School in Biomedical Sciences and Engineering, University of Maine, Orono, ME 04469, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1111\/apm.12128","article-title":"The Human JC Polyomavirus (JCPyV): Virological Background and Clinical Implications","volume":"121","author":"Hirsch","year":"2013","journal-title":"APMIS"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1016\/S0140-6736(71)91777-6","article-title":"Cultivation of Papova-like Virus from Human Brain with Progressive Multifocal Leucoencephalopathy","volume":"1","author":"Padgett","year":"1971","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/BF00686519","article-title":"Electron Microscopic Observations on a Case of Progressive Multifocal Leukoencephalopathy","volume":"5","author":"Silverman","year":"1965","journal-title":"Acta Neuropathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1126\/science.148.3676.1477","article-title":"Particles Resembling Papova Viruses in Human Cerebral Demyelinating Disease","volume":"148","author":"Zurhein","year":"1965","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"5323","DOI":"10.1172\/JCI76629","article-title":"Human Glial Chimeric Mice Reveal Astrocytic Dependence of JC Virus Infection","volume":"124","author":"Kondo","year":"2014","journal-title":"J. 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