{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T03:02:23Z","timestamp":1789786943992,"version":"4.0.1"},"reference-count":58,"publisher":"American Society for Microbiology","issue":"14","license":[{"start":{"date-parts":[[2016,6,24]],"date-time":"2016-06-24T00:00:00Z","timestamp":1466726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,7,15]],"date-time":"2016-07-15T00:00:00Z","timestamp":1468540800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["5R37AI15122"],"award-info":[{"award-number":["5R37AI15122"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2016,7,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The specificity of encapsidation of C-cluster enteroviruses depends on an interaction between capsid proteins and nonstructural protein 2C\n            <jats:sup>ATPase<\/jats:sup>\n            . In particular, residue N\n            <jats:sub>252<\/jats:sub>\n            of poliovirus 2C\n            <jats:sup>ATPase<\/jats:sup>\n            interacts with VP3 of coxsackievirus A20, in the context of a chimeric virus. Poliovirus 2C\n            <jats:sup>ATPase<\/jats:sup>\n            has important roles both in RNA replication and encapsidation. In this study, we searched for additional sites in 2C\n            <jats:sup>ATPase<\/jats:sup>\n            , near N\n            <jats:sub>252<\/jats:sub>\n            , that are required for encapsidation. Accordingly, segments adjacent to N\n            <jats:sub>252<\/jats:sub>\n            were analyzed by combining triple and single alanine mutations to identify residues required for function. Two triple alanine mutants exhibited defects in RNA replication. The remaining two mutations, located in secondary structures in a predicted three-dimensional model of 2C\n            <jats:sup>ATPase<\/jats:sup>\n            , caused lethal growth phenotypes. Most single alanine mutants, derived from the lethal variants, were either quasi-infectious and yielded variants with wild-type (wt) or temperature-sensitive (\n            <jats:italic>ts<\/jats:italic>\n            ) growth phenotypes or had a lethal growth phenotype due to defective RNA replication. The K\n            <jats:sub>259<\/jats:sub>\n            A mutation, mapping to an \u03b1 helix in the predicted structure of 2C\n            <jats:sup>ATPase<\/jats:sup>\n            , resulted in a cold-sensitive virus.\n            <jats:italic>In vivo<\/jats:italic>\n            protein synthesis and virus production were strikingly delayed at 33\u00b0C relative to the wt, suggesting a defect in uncoating. Studies with a reporter virus indicated that this mutant is also defective in encapsidation at 33\u00b0C. Cell imaging confirmed a much-reduced production of K\n            <jats:sub>259<\/jats:sub>\n            A mature virus at 33\u00b0C relative to the wt. In conclusion, we have for the first time linked a cold-sensitive encapsidation defect in 2C\n            <jats:sup>ATPase<\/jats:sup>\n            (K\n            <jats:sub>259<\/jats:sub>\n            A) to a subsequent delay in uncoating of the virus particle at 33\u00b0C during the next cycle of infection.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Enterovirus morphogenesis, which involves the encapsidation of newly made virion RNA, is a process still poorly understood. Elucidation of this process is important for future drug development for a large variety of diseases caused by these agents. We have previously shown that the specificity of encapsidation of poliovirus and of C-cluster coxsackieviruses, which are prototypes of enteroviruses, is dependent on an interaction of capsid proteins with the multifunctional nonstructural protein 2C\n            <jats:sup>ATPase<\/jats:sup>\n            . In this study, we have searched for residues in poliovirus 2C\n            <jats:sup>ATPase<\/jats:sup>\n            , near a presumed capsid-interacting site, important for encapsidation. An unusual cold-sensitive mutant of 2C\n            <jats:sup>ATPase<\/jats:sup>\n            possessed a defect in encapsidation at 37\u00b0C and subsequently in uncoating during the next cycle of infection at 33\u00b0C. These studies not only reveal a new site in 2C\n            <jats:sup>ATPase<\/jats:sup>\n            that is involved in encapsidation but also identify a link between encapsidation and uncoating.\n          <\/jats:p>","DOI":"10.1128\/jvi.02877-15","type":"journal-article","created":{"date-parts":[[2016,4,14]],"date-time":"2016-04-14T03:54:02Z","timestamp":1460606042000},"page":"6174-6186","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":26,"title":["A Single Amino Acid Substitution in Poliovirus Nonstructural Protein 2C\n            <sup>ATPase<\/sup>\n            Causes Conditional Defects in Encapsidation and Uncoating"],"prefix":"10.1128","volume":"90","author":[{"given":"Emmanuel","family":"Asare","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JoAnn","family":"Mugavero","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eckard","family":"Wimmer","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aniko V.","family":"Paul","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.64.3.1102-1107.1990"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1994.1329"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1995.1010"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-73-8-1977"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.11.8482-8489.1997"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.62.11.4016-4021.1988"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1994.1111"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.12.8962-8972.1997"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.11.8759-8765.1997"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001066"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00012-14"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00914-12"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.062497-0"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.8.14.1726"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.1.427-435.1999"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-7091-7000-7"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.13.2.403"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-27-3-329"},{"key":"e_1_3_2_20_2","first-page":"149","article-title":"Studies on the in vitro uncoating of poliovirus. 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