{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,6,10]],"date-time":"2024-06-10T08:35:52Z","timestamp":1718008552950},"reference-count":85,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2014,5,15]],"date-time":"2014-05-15T00:00:00Z","timestamp":1400112000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2014,5,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>The tripartite motif (TRIM) family of proteins includes the TRIM5\u03b1 antiretroviral restriction factor. TRIM5\u03b1 from many Old World and some New World monkeys can restrict the human immunodeficiency virus type 1 (HIV-1), while human TRIM5\u03b1 restricts N-tropic murine leukemia virus (N-MLV). TRIM5\u03b1 forms highly dynamic cytoplasmic bodies (CBs) that associate with and translocate on microtubules. However, the functional involvement of microtubules or other cytoskeleton-associated factors in the viral restriction process had not been shown. Here, we demonstrate the dependency of TRIM5\u03b1-mediated restriction on microtubule-mediated transport. Pharmacological disruption of the microtubule network using nocodazole or disabling it using paclitaxel (originally named taxol) decreased the restriction of N-MLV and HIV-1 by human or simian alleles of TRIM5\u03b1, respectively. In addition, pharmacological inhibition of dynein motor complexes using erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and small interfering RNA-mediated depletion of the dynein heavy chain (DHC) similarly decreased TRIM5\u03b1-mediated restriction. The loss in restriction resulting from either the disassembly of microtubules or the disruption of dynein motor activity was seen for both endogenous and overexpressed TRIM5\u03b1 and was not due to differences in protein stability or cell viability. Both nocodazole treatment and DHC depletion interfered with the dynamics of TRIM5\u03b1 CBs, increasing their size and altering their intracellular localization. In addition, nocodazole, paclitaxel, and DHC depletion were all found to increase the stability of HIV-1 cores in infected cells, providing an alternative explanation for the decreased restriction. In conclusion, association with microtubules and the translocation activity of dynein motor complexes are required to achieve efficient restriction by TRIM5\u03b1.<\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            The primate innate cellular defenses against infection by retroviruses include a protein named TRIM5\u03b1, belonging to the family of restriction factors. TRIM5\u03b1 is present in the cytoplasm, where it can intercept incoming retroviruses shortly after their entry. How TRIM5\u03b1 manages to be present at the appropriate subcytoplasmic location to interact with its target is unknown. We hypothesized that TRIM5\u03b1, either as a soluble protein or a high-molecular-weight complex (the cytoplasmic body), is transported within the cytoplasm by a molecular motor called the dynein complex, which is known to interact with and move along microtubules. Our results show that destructuring microtubules or crippling their function decreased the capacity of human or simian TRIM5\u03b1 to restrict their retroviral targets. Inhibiting dynein motor activity, or reducing the expression of a key component of this complex, similarly affected TRIM5\u03b1-mediated restriction. Thus, we have identified specific cytoskeleton structures involved in innate antiretroviral defenses.\n          <\/jats:p>","DOI":"10.1128\/jvi.03717-13","type":"journal-article","created":{"date-parts":[[2014,3,6]],"date-time":"2014-03-06T04:16:26Z","timestamp":1394079386000},"page":"5661-5676","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":23,"title":["Functional Evidence for the Involvement of Microtubules and Dynein Motor Complexes in TRIM5\u03b1-Mediated Restriction of Retroviruses"],"prefix":"10.1128","volume":"88","author":[{"given":"Paulina","family":"Pawlica","sequence":"first","affiliation":[{"name":"Laboratory of Retrovirology, Department of Medical Biology and BioMed Group, Universit\u00e9 du Qu\u00e9bec \u00e0 Trois-Rivi\u00e8res, Trois-Rivi\u00e8res, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valerie","family":"Le Sage","sequence":"additional","affiliation":[{"name":"HIV-1 RNA Trafficking Laboratory, Lady Davis Institute at the Jewish General Hospital and Department of Medicine, McGill University, Montr\u00e9al, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nolwenn","family":"Poccardi","sequence":"additional","affiliation":[{"name":"Laboratory of Retrovirology, Department of Medical Biology and BioMed Group, Universit\u00e9 du Qu\u00e9bec \u00e0 Trois-Rivi\u00e8res, Trois-Rivi\u00e8res, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel J.","family":"Tremblay","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Infectiologie, Centre de Recherche du CHU de l'Universit\u00e9 Laval, Qu\u00e9bec, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew J.","family":"Mouland","sequence":"additional","affiliation":[{"name":"HIV-1 RNA Trafficking Laboratory, Lady Davis Institute at 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