{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:37:34Z","timestamp":1791416254075,"version":"4.3.3"},"reference-count":31,"publisher":"National Academy of Sciences","issue":"24","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2005,6,14]]},"abstract":"<jats:p>\n                    <jats:italic>Trypanosoma brucei<\/jats:italic>\n                    is a protozoan parasite that causes African sleeping sickness.\n                    <jats:italic>T. brucei<\/jats:italic>\n                    multiplies extracellularly in the bloodstream, relying on antigenic variation of a dense variant surface glycoprotein (VSG) coat to escape antibody-mediated lysis. We investigated the role of VSG in proliferation and pathogenicity by using inducible RNA interference to ablate\n                    <jats:italic>VSG<\/jats:italic>\n                    transcript down to 1-2% normal levels. Inhibiting VSG synthesis\n                    <jats:italic>in vitro<\/jats:italic>\n                    triggers a rapid and specific cell cycle checkpoint blocking cell division. Parasites arrest at a discrete precytokinesis stage with two full-length flagella and opposing flagellar pockets, without undergoing additional rounds of S phase and mitosis. A subset (&lt;10%) of the stalled cells have internal flagella, indicating that the progenitors of these cells were already committed to cytokinesis when VSG restriction was sensed. Although there was no obvious VSG depletion\n                    <jats:italic>in vitro<\/jats:italic>\n                    after 24-h induction of\n                    <jats:italic>VSG<\/jats:italic>\n                    RNA interference, there was rapid clearance of these cells\n                    <jats:italic>in vivo<\/jats:italic>\n                    . We propose that a stringent block in VSG synthesis produces stalled trypanosomes with a minimally compromised VSG coat, which can be targeted by the immune system. Our data indicate that VSG protein or transcript is monitored during cell cycle progression in bloodstream-form\n                    <jats:italic>T. brucei<\/jats:italic>\n                    and describes precise precytokinesis cell cycle arrest. This checkpoint before cell division provides a link between the protective VSG coat and cell cycle progression and could function as a novel parasite safety mechanism, preventing extensive dilution of the protective VSG coat in the absence of VSG synthesis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0501886102","type":"journal-article","created":{"date-parts":[[2005,6,3]],"date-time":"2005-06-03T20:24:58Z","timestamp":1117830298000},"page":"8716-8721","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":124,"title":["Variant surface glycoprotein RNA interference triggers a precytokinesis cell cycle arrest in African trypanosomes"],"prefix":"10.1073","volume":"102","author":[{"given":"Karen","family":"Sheader","sequence":"first","affiliation":[{"name":"Peter Medawar Building for Pathogen Research, University of Oxford, South Parks Road, Oxford OX1 3SY, United Kingdom; and Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sue","family":"Vaughan","sequence":"additional","affiliation":[{"name":"Peter Medawar Building for Pathogen Research, University of Oxford, South Parks Road, Oxford OX1 3SY, United Kingdom; and Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Minchin","sequence":"additional","affiliation":[{"name":"Peter Medawar Building for Pathogen Research, University of Oxford, South Parks Road, Oxford OX1 3SY, United Kingdom; and Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie","family":"Hughes","sequence":"additional","affiliation":[{"name":"Peter Medawar Building for Pathogen Research, University of Oxford, South Parks Road, Oxford OX1 3SY, United Kingdom; and Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Gull","sequence":"additional","affiliation":[{"name":"Peter Medawar Building for Pathogen Research, University of Oxford, South Parks Road, Oxford OX1 3SY, United Kingdom; and Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Rudenko","sequence":"additional","affiliation":[{"name":"Peter Medawar Building for Pathogen Research, University of Oxford, South Parks Road, Oxford OX1 3SY, United Kingdom; and Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2005,6,3]]},"reference":[{"key":"e_1_3_2_1_2","unstructured":"World Health Organization (2001) African Trypanosomiasis or Sleeping Sickness Fact Sheet 259 (W.H.O. 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