{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T03:29:19Z","timestamp":1792726159133,"version":"4.5.0"},"reference-count":36,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2002,5,15]],"date-time":"2002-05-15T00:00:00Z","timestamp":1021420800000},"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":[[2002,5,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Little is known about the function of flavivirus nonstructural protein NS2A. Two forms of NS2A are found in yellow fever virus-infected cells. Full-length NS2A (224 amino acids) is the product of cleavage at the NS1\/2A and NS2A\/2B sites. NS2A\u03b1, a C-terminally truncated form of 190 amino acids, results from partial cleavage by the viral NS2B-3 serine protease at the sequence QK\u2193T within NS2A. Exchange of serine for lysine at this site (QKT\u2192QST) blocks the production of both NS2A\u03b1 and infectious virus. The present study reveals that this defect is not at the level of RNA replication. Despite normal structural region processing, infectious particles containing genome RNA and capsid protein were not released from cells transfected with the mutant RNA. Nevertheless, production of subviral prM\/M- and E-containing particles was unimpaired. The NS2A defect could be complemented in\n            <jats:italic>trans<\/jats:italic>\n            by providing NS1-2A or NS1-2A\u03b1. However,\n            <jats:italic>trans<\/jats:italic>\n            complementation was not observed when the C-terminal lysine of NS1-2A\u03b1 was replaced with serine. In addition to true reversions, NS2A\u03b1 cleavage site mutations could be suppressed by two classes of second-site changes. The first class consisted of insertions at the NS2A\u03b1 cleavage site that restored its basic character and cleavability. A second class of suppressors occurred in the NS3 helicase domain, in which NS3 aspartate 343 was replaced with an uncharged residue (either valine, alanine, or glycine). These mutations in NS3 restored infectious-virus production in the absence of cleavage at the mutant NS2A\u03b1 site. Taken together, our results reveal an unexpected role for NS2A and NS3 in the assembly and\/or release of infectious flavivirus particles.\n          <\/jats:p>","DOI":"10.1128\/jvi.76.10.4773-4784.2002","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T10:09:14Z","timestamp":1027764554000},"page":"4773-4784","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":263,"title":["Mutations in the Yellow Fever Virus Nonstructural Protein NS2A Selectively Block Production of Infectious Particles"],"prefix":"10.1128","volume":"76","author":[{"given":"Beate M.","family":"Ku\u0308mmerer","sequence":"first","affiliation":[{"name":"Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, New York 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles M.","family":"Rice","sequence":"additional","affiliation":[{"name":"Laboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, New York 10021"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.22.12989"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.9.5816-5820.1995"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.68.6.3794-3802.1994"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.10.8083-8094.1999"},{"key":"e_1_3_2_6_2","first-page":"1043","volume":"1","year":"2001","unstructured":"Burke, D. 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