{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,22]],"date-time":"2025-03-22T09:52:19Z","timestamp":1742637139197},"reference-count":90,"publisher":"American Society for Microbiology","issue":"16","license":[{"start":{"date-parts":[[2014,8,15]],"date-time":"2014-08-15T00:00:00Z","timestamp":1408060800000},"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":[[2014,8,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Genomes of positive (+)-strand RNA viruses use\n            <jats:italic>cis<\/jats:italic>\n            -acting signals to direct both translation and replication. Here we examine two 5\u2032-proximal\n            <jats:italic>cis<\/jats:italic>\n            -replication signals of different character in a defective interfering (DI) RNA of the bovine coronavirus (BCoV) that map within a 322-nucleotide (nt) sequence (136 nt from the genomic 5\u2032 untranslated region and 186 nt from the nonstructural protein 1 [nsp1]-coding region) not found in the otherwise-identical nonreplicating subgenomic mRNA7 (sgmRNA7). The natural DI RNA is structurally a fusion of the two ends of the BCoV genome that results in a single open reading frame between a partial nsp1-coding region and the entire N gene. (i) In the first examination, mutation analyses of a recently discovered long-range RNA-RNA base-paired structure between the 5\u2032 untranslated region and the partial nsp1-coding region showed that it, possibly in concert with adjacent stem-loops, is a\n            <jats:italic>cis<\/jats:italic>\n            -acting replication signal in the (+) strand. We postulate that the higher-order structure promotes (+)-strand synthesis. (ii) In the second examination, analyses of multiple frame shifts, truncations, and point mutations within the partial nsp1-coding region showed that synthesis of a PEFP core amino acid sequence within a group A lineage betacoronavirus-conserved NH\n            <jats:sub>2<\/jats:sub>\n            -proximal WAPEFPWM domain is required in\n            <jats:italic>cis<\/jats:italic>\n            for DI RNA replication. We postulate that the nascent protein, as part of an RNA-associated translating complex, acts to direct the DI RNA to a critical site, enabling RNA replication. We suggest that these results have implications for viral genome replication and explain, in part, why coronavirus sgmRNAs fail to replicate.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            <jats:italic>cis<\/jats:italic>\n            -Acting RNA and protein structures that regulate (+)-strand RNA virus genome synthesis are potential sites for blocking virus replication. Here we describe two: a previously suspected 5\u2032-proximal long-range higher-order RNA structure and a novel nascent NH\n            <jats:sub>2<\/jats:sub>\n            -terminal protein component of nsp1 that are common among betacoronaviruses of group A lineage.\n          <\/jats:p>","DOI":"10.1128\/jvi.00738-14","type":"journal-article","created":{"date-parts":[[2014,5,29]],"date-time":"2014-05-29T08:07:20Z","timestamp":1401350840000},"page":"8868-8882","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["Dependence of Coronavirus RNA Replication on an NH\n            <sub>2<\/sub>\n            -Terminal Partial Nonstructural Protein 1 in\n            <i>cis<\/i>"],"prefix":"10.1128","volume":"88","author":[{"given":"Yu-Pin","family":"Su","sequence":"first","affiliation":[{"name":"Department of Biomedical and Diagnostic Sciences, University of Tennessee College of Veterinary Medicine, Knoxville, 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