{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T19:49:34Z","timestamp":1789674574106,"version":"4.0.1"},"reference-count":67,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,5,6]],"date-time":"2015-05-06T00:00:00Z","timestamp":1430870400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"The Ministry of Health, Labour and Welfare, Japan"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropathology"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:p>\n                    Progressive multifocal leukoencephalopathy (\n                    <jats:styled-content style=\"fixed-case\">PML<\/jats:styled-content>\n                    ) is a fatal demyelinating disease caused by reactivation of the asymptomatic persistent pathogen human polyomavirus\n                    <jats:styled-content style=\"fixed-case\">JC<\/jats:styled-content>\n                    (\n                    <jats:styled-content style=\"fixed-case\">JC<\/jats:styled-content>\n                    virus). The pathology of affected brain tissues demonstrates oligodendroglia\u2010like cells with viral inclusions in their enlarged nuclei, a diagnostic hallmark of this disease. Today, the pathological features of this disease are expanding, partly due to an unsteady balance between viral virulence and host immunity. Intranuclear viral inclusions were initially thought to be amphophilic materials comprising the entire enlarged nucleus, based on\n                    <jats:styled-content style=\"fixed-case\">HE<\/jats:styled-content>\n                    staining (full inclusions). Howevewr, recent immunohistochemical analyses detected the presence of intranuclear viral inclusions in dots (dot\u2010shaped inclusions). The dot\u2010shaped inclusions reflect clustered progeny virions at punctuated subnuclear domains called promyelocytic leukemia nuclear bodies, and are indicative of early\u2010stage viral infection or suppressed viral proliferation. Second, the\n                    <jats:styled-content style=\"fixed-case\">JC<\/jats:styled-content>\n                    virus is usually reactivated in patients with impaired immunity, and therefore the inflammatory reactions are poor. However, the causes of immunosuppression are divergent, as seen with the frequent use of immunosuppressive drugs, including natalizumab. Therefore, the degree of host immunity is variable; some patients show marked anti\u2010viral inflammatory reactions and a good prognosis, indicating that a strong resistance against viral infection remains. Recovery of the immune system may also induce paradoxical clinical worsening, known as immune reconstitution inflammatory syndrome, the mechanism of which has not been clarified. The virus\u2010host interactions have increased in complexity, and the pathology of\n                    <jats:styled-content style=\"fixed-case\">PML<\/jats:styled-content>\n                    is diverging. In this review, the pathology of\n                    <jats:styled-content style=\"fixed-case\">PML<\/jats:styled-content>\n                    will be described, with a focus on the intranuclear target of\n                    <jats:styled-content style=\"fixed-case\">JC<\/jats:styled-content>\n                    virus infection and host inflammatory reactions.\n                  <\/jats:p>","DOI":"10.1111\/neup.12203","type":"journal-article","created":{"date-parts":[[2015,5,6]],"date-time":"2015-05-06T10:42:59Z","timestamp":1430908979000},"page":"487-496","source":"Crossref","is-referenced-by-count":13,"title":["Progressive multifocal leukoencephalopathy: Dot\u2010shaped inclusions and virus\u2010host interactions"],"prefix":"10.1111","volume":"35","author":[{"given":"Yukiko","family":"Shishido\u2010Hara","sequence":"first","affiliation":[{"name":"Department of Pathology School of Medicine Kyorin University  Tokyo Japan"},{"name":"Laboratory of Structural Neuropathology Tokyo Metropolitan Institute of Medical Science  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,5,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/81.1.93"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(59)91774-X"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00686519"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.148.3676.1477"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(71)91777-6"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.211583"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.181.4100.674"},{"key":"e_1_2_8_9_1","first-page":"718","article-title":"Differential neurooncogenicity of strains of JC virus, a human polyoma virus, in newborn Syrian hamsters","volume":"37","author":"Padgett BL","year":"1977","journal-title":"Cancer Res"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)62505-6"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10827"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.20933"},{"key":"e_1_2_8_13_1","first-page":"333","article-title":"Progressive multifocal leukoencephalopathy. 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