{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T15:27:05Z","timestamp":1766158025945,"version":"3.37.3"},"reference-count":55,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,4,6]],"date-time":"2017-04-06T00:00:00Z","timestamp":1491436800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NS079172","NS074916","P30AI087714","NS041218"],"award-info":[{"award-number":["NS079172","NS074916","P30AI087714","NS041218"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>The human immunodeficiency virus (HIV) envelope protein gp120 promotes axonal damage and neurite pruning, similar to that observed in HIV\u2010positive subjects with neurocognitive disorders. Thus, gp120 has been used to examine molecular and cellular pathways underlying HIV\u2010mediated neuronal dysfunction. Gp120 binds to tubulin beta III, a component of neuronal microtubules. Microtubule function, which modulates the homeostasis of neurons, is regulated by polymerization and post\u2010translational modifications. Based on these considerations, we tested the hypothesis that gp120 induces dynamic instability of neuronal microtubules. We first observed that gp120 prevents the normal polymerization of tubulin <jats:italic>in\u00a0vitro<\/jats:italic>. We then tested whether gp120 alters the post\u2010translational modifications in tubulin by examining the ability of gp120 to change the levels of acetylated tubulin in primary rat neuronal cultures. Gp120 elicited a time\u2010dependent decrease in tubulin acetylation that\u00a0was reversed by Helix\u2010A peptide, a compound that competitively displaces the binding of gp120 to neuronal microtubules. To determine whether post\u2010translational modifications in tubulin also occur <jats:italic>in\u00a0vivo<\/jats:italic>, we measured acetylated tubulin in the cerebral cortex of HIV transgenic rats (HIV\u2010tg). We observed a decrease in tubulin acetylation in 5\u2010 and 9\u2010month\u2010old HIV\u2010tg rats when compared to age\u2010matched wild type. Neither changes in microglia morphology nor alterations in mRNA levels for interleukin\u20101\u03b2 and tumor necrosis factor \u03b1 were detected in 5\u2010month\u2010old animals. Our findings propose neuronal microtubule instability as a novel mechanism of HIV neurotoxicity, without evidence of enhanced inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc14015-fig-0007-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.14015","type":"journal-article","created":{"date-parts":[[2017,3,10]],"date-time":"2017-03-10T23:07:04Z","timestamp":1489187224000},"page":"606-613","source":"Crossref","is-referenced-by-count":26,"title":["The viral protein gp120 decreases the acetylation of neuronal tubulin: potential mechanism of 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