{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T13:16:45Z","timestamp":1785417405503,"version":"3.56.0"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"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":["mSphere"],"published-print":{"date-parts":[[2026,5,26]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Toxoplasma gondii<\/jats:italic>\n                      , which can virtually infect all warm-blooded cells, secretes various virulence factors to evade interferon-gamma (IFN-\u03b3)-dependent host immunity. While these secreted proteins are widely characterized, the molecular mechanisms important for virulence within the parasite are unclear. In this study, we aimed to investigate the roles of non-secretory proteins of\n                      <jats:italic toggle=\"yes\">T. gondii<\/jats:italic>\n                      in immunosuppression. Deletion of deubiquitinase TgJosephin resulted in attenuated virulence in wild-type mice but not in mice lacking the interferon-gamma receptor (IFN\u03b3R). Moreover, TgJosephin expression was maintained by TgRad23, a protein involved in DNA repair and protein shuttling. Notably, TgJosephin depletion increased ubiquitination of subpellicular microtubule protein 1 (SPM1), a stabilizing component of the parasite microtubules, and mutating its ubiquitination sites restored virulence in the absence of TgJosephin. We propose TgJosephin as a novel virulence factor maintained by TgRad23 and a virulence pathway involving SPM1 metabolism.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        <jats:italic toggle=\"yes\">Toxoplasma gondii<\/jats:italic>\n                        is an obligate parasite whose infection can be detrimental when combined with pregnancy or immunodeficiency. Studies on\n                        <jats:italic toggle=\"yes\">T. gondii<\/jats:italic>\n                        virulence have revealed various secretory proteins that inhibit the host interferon-gamma (IFN-\u03b3) immune response. However, much of the broader virulence landscape remains unclear. To explore the unknown molecular pathways of\n                        <jats:italic toggle=\"yes\">T. gondii<\/jats:italic>\n                        virulence in mice, we searched for immunosuppressive functions in genes encoding non-secretory proteins, associated with fundamental cellular processes of the virulent type I strain. Here, we found that TgJosephin, a highly conserved deubiquitinase, was important for virulence in wild-type mice but not mice lacking the IFN-\u03b3 receptor (IFN\u03b3R). In addition, TgJosephin expression was dependent on TgRad23, and loss of TgJosephin led to increased ubiquitination of a microtubule protein SPM1. Our results suggest a novel anti-IFN-\u03b3 pathway of\n                        <jats:italic toggle=\"yes\">T. gondii<\/jats:italic>\n                        mediated by TgJosephin and SPM1 deubiquitination.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/msphere.00137-26","type":"journal-article","created":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T13:00:26Z","timestamp":1776085226000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["TgJosephin and TgRad23 are important for anti-IFN-\u03b3 virulence via deubiquitination of SPM1 in\n                    <i>Toxoplasma<\/i>"],"prefix":"10.1128","volume":"11","author":[{"given":"Emi","family":"Hashizaki","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/035t8zc32","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Immunoparasitology, Research Institute 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