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Within this clinical spectrum, HIV\u2010associated ataxia is an uncommon but debilitating disorder with poorly defined neuropathological mechanisms. This study investigated two rhesus macaques with chronic simian immunodeficiency virus (SIV) infection that developed progressive ataxia, characterized by postural imbalance and nystagmus. Comparative neuropathological profiling of cerebellar tissue from ataxic SIV\u2010infected macaques, non\u2010ataxic SIV\u2010infected macaques, and uninfected controls revealed that ataxia was associated with diffuse cerebellar atrophy, disrupted tissue organization, Purkinje cell degeneration, demyelination, glial nodule formation, and prominent microglial neuroinflammation. Cerebellar infection with simian polyomavirus 40 (SV40), a member of the\n                    <jats:italic>Polyomaviridae<\/jats:italic>\n                    family, was identified as the cause of the lesions, with viral tropism primarily involving cerebellar granule neurons. Mechanistically, SV40 infection induced neuronal pyroptosis and inflammatory cytokine release, promoting microglial recruitment and activation, amplifying local neuroinflammation, and culminating in nodular aggregate formation. Collectively, these findings establish SV40 infection as a direct driver of cerebellar pathology in SIV\u2010associated ataxia and define a pathogenic sequence linking granule neuron pyroptosis, microglial activation, and progressive cerebellar injury\u2014a cascade that may parallel polyomavirus\u2010induced ataxia in people living with HIV\u20101.\n                  <\/jats:p>","DOI":"10.1002\/mco2.71049","type":"journal-article","created":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T17:03:01Z","timestamp":1792429381000},"source":"Crossref","is-referenced-by-count":0,"title":["Polyomavirus Drives Cerebellar Lesions in AIDS Monkeys With Ataxia"],"prefix":"10.1002","volume":"7","author":[{"given":"Tian\u2010Zhang","family":"Song","sequence":"first","affiliation":[{"name":"State Key Laboratory of Genetic Evolution &amp; Animal Models National Resource Center For Non\u2010Human Primates Kunming Institute of Zoology Chinese Academy of Sciences  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li\u2010Rong","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Evolution &amp; Animal Models National Resource Center For Non\u2010Human Primates Kunming Institute of Zoology Chinese Academy of Sciences  Kunming China"},{"name":"KIZ\u2010SU Joint Laboratory of Animal Model and Drug Development College of Pharmaceutical Sciences Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun\u2010Mei","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Evolution &amp; Animal Models National Resource Center For Non\u2010Human Primates Kunming Institute of Zoology Chinese Academy of Sciences  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Hu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Evolution &amp; Animal Models National Resource Center For Non\u2010Human Primates Kunming Institute of Zoology Chinese Academy of Sciences  Kunming China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Evolution &amp; Animal Models National Resource Center For Non\u2010Human Primates Kunming Institute of Zoology Chinese Academy of Sciences  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u2010Rong","family":"Tian","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Evolution &amp; Animal Models National Resource Center For Non\u2010Human Primates Kunming Institute of Zoology Chinese Academy of Sciences  Kunming China"},{"name":"Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&amp;D College of Pharmacy Dali University  Dali China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu\u2010Meng","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Evolution &amp; Animal Models National Resource Center For Non\u2010Human Primates Kunming Institute of Zoology Chinese Academy of Sciences  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si\u2010Dong","family":"Xiong","sequence":"additional","affiliation":[{"name":"KIZ\u2010SU Joint Laboratory of Animal Model and Drug Development College of Pharmaceutical Sciences Soochow University  Suzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong\u2010Dong","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Evolution &amp; 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