{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T14:51:30Z","timestamp":1715957490283},"reference-count":24,"publisher":"Microbiology Society","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,3,1]]},"abstract":"<jats:p>Mature protein C of tick-borne encephalitis virus (TBEV) is cleaved from the polyprotein precursor by the viral NS2B\/3 protease (NS2B\/3<jats:sup>pro<\/jats:sup>). We showed previously that replacement of the NS2B\/3<jats:sup>pro<\/jats:sup> cleavage site at the C terminus of protein C by the foot-and-mouth disease virus (FMDV) 2A StopGo sequence leads to the production of infectious virions. Here, we show that infectious virions can also be produced from a TBEV mutant bearing an inactivated 2A sequence through the expression of the FMDV 3C protease (3C<jats:sup>pro<\/jats:sup>) either <jats:italic>in cis<\/jats:italic> or <jats:italic>in trans<\/jats:italic> (from a TBEV replicon). Cleavage at the C terminus of protein C depended on the catalytic activity of 3C<jats:sup>pro<\/jats:sup> as well as on the presence of an optimized 3C<jats:sup>pro<\/jats:sup> cleavage site. Passage of the TBEV mutants bearing a 3C<jats:sup>pro<\/jats:sup> cleavage site either in the absence of 3C<jats:sup>pro<\/jats:sup> or in the presence of a catalytically inactive 3C<jats:sup>pro<\/jats:sup> led to the appearance of revertants in which protein C cleavage by NS2B\/3<jats:sup>pro<\/jats:sup> had been regained. In three different revertants, a cleavage site for NS2B\/3<jats:sup>pro<\/jats:sup>, namely RR*C, was now present, leading to an elongated protein C. Furthermore, two revertants acquired additional mutations in the C terminus of protein C, eliminating two basic residues. Although these latter mutants showed wild-type levels of early RNA synthesis, their foci were smaller and an accumulation of protein C in the cytoplasm was observed. These findings suggest a role of the positive charge of the C terminus of protein C for budding of the nucleocapsid and further support the notion that TBEV protein C is a multifunctional protein.<\/jats:p>","DOI":"10.1099\/vir.0.038398-0","type":"journal-article","created":{"date-parts":[[2011,12,2]],"date-time":"2011-12-02T09:25:34Z","timestamp":1322817934000},"page":"504-515","source":"Crossref","is-referenced-by-count":2,"title":["Generation and genetic stability of tick-borne encephalitis virus mutants dependent on processing by the foot-and-mouth disease virus 3C protease"],"prefix":"10.1099","volume":"93","author":[{"given":"Sabrina","family":"Schrauf","sequence":"first","affiliation":[{"name":"Institute of Virology, Medical University of Vienna, Kinderspitalgasse 15, A-1095 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Kurz","sequence":"additional","affiliation":[{"name":"Max F. Perutz Laboratories, Medical University of Vienna, Dr. Bohr-Gasse 9\/3, A-1030 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Taucher","sequence":"additional","affiliation":[{"name":"Institute of Virology, Medical University of Vienna, Kinderspitalgasse 15, A-1095 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian W.","family":"Mandl","sequence":"additional","affiliation":[{"name":"Institute of Virology, Medical University of Vienna, Kinderspitalgasse 15, A-1095 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim","family":"Skern","sequence":"additional","affiliation":[{"name":"Max F. 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