{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:59:42Z","timestamp":1791939582938,"version":"4.3.4"},"reference-count":72,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2009,1,15]],"date-time":"2009-01-15T00:00:00Z","timestamp":1231977600000},"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":[[2009,1,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The influenza A virus nucleoprotein (NP) is a single-stranded RNA-binding protein that encapsidates the virus genome and has essential functions in viral-RNA synthesis. Here, we report the characterization of a temperature-sensitive (\n            <jats:italic>ts<\/jats:italic>\n            ) NP mutant (US3) originally generated in fowl plague virus (A\/chicken\/Rostock\/34). Sequence analysis revealed a single mutation, M239L, in NP, consistent with earlier mapping studies assigning the\n            <jats:italic>ts<\/jats:italic>\n            lesion to segment 5. Introduction of this mutation into A\/PR\/8\/34 virus by reverse genetics produced a\n            <jats:italic>ts<\/jats:italic>\n            phenotype, confirming the identity of the lesion. Despite an approximately 100-fold drop in the viral titer at the nonpermissive temperature, the mutant US3 polypeptide supported wild-type (WT) levels of genome transcription, replication, and protein synthesis, indicating a late-stage defect in function of the NP polypeptide. Nucleocytoplasmic trafficking of the US3 NP was also normal, and the virus actually assembled and released around sixfold more virus particles than the WT virus, with normal viral-RNA content. However, the particle\/PFU ratio of these virions was 50-fold higher than that of WT virus, and many particles exhibited an abnormal morphology. Reverse-genetics studies in which A\/PR\/8\/34 segment 7 was swapped with sequences from other strains of virus revealed a profound incompatibility between the M239L mutation and the A\/Udorn\/72 M1 gene, suggesting that the\n            <jats:italic>ts<\/jats:italic>\n            mutation affects M1-NP interactions. Thus, we have identified a late-acting defect in NP that, separate from its function in RNA synthesis, indicates a role for the polypeptide in virion assembly, most likely involving M1 as a partner.\n          <\/jats:p>","DOI":"10.1128\/jvi.01424-08","type":"journal-article","created":{"date-parts":[[2008,11,6]],"date-time":"2008-11-06T01:46:47Z","timestamp":1225936007000},"page":"562-571","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":41,"title":["Studies of an Influenza A Virus Temperature-Sensitive Mutant Identify a Late Role for NP in the Formation of Infectious Virions"],"prefix":"10.1128","volume":"83","author":[{"given":"Sarah L.","family":"Noton","sequence":"first","affiliation":[{"name":"Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha","family":"Simpson-Holley","sequence":"additional","affiliation":[{"name":"Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Medcalf","sequence":"additional","affiliation":[{"name":"Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen M.","family":"Wise","sequence":"additional","affiliation":[{"name":"Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward C.","family":"Hutchinson","sequence":"additional","affiliation":[{"name":"Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"McCauley","sequence":"additional","affiliation":[{"name":"Institute for Animal Health, Compton Laboratory, Berkshire RG20 7NN, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Digard","sequence":"additional","affiliation":[{"name":"Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg449"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.18.8709-8719.2000"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(77)90058-7"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(79)90146-6"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2006.00507.x"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.4.2947-2958.1997"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.17.6282"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.7.5493-5501.1998"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2006.09.013"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.18803-0"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1993.1435"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.2.1262-1270.2005"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2004.00237.x"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2007.11.008"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01184-08"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00361-07"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422X-3-58"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2004.02.028"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.3.2222-2231.1999"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-10-3-457"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2003.12.009"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1098\/rsbl.2004.0253"},{"key":"e_1_3_2_24_2","first-page":"1","year":"2006","unstructured":"Elton, D., P. Digard, L. Tiley, and J. Ortin. 2006. Structure and function of the influenza virus RNP, p. 1-36. In E. Yawaoka (ed.), Influenza virology: current topics. Caister Academic Press, Wymondham, United Kingdom.","journal-title":"Influenza virology: current topics"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.9.7357-7367.1999"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.1.408-419.2001"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkm087"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.24.11538-11547.2000"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0607614103"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.jbchem.a122569"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.64.11.5669-5673.1990"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01634-08"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.20.11007-11015.2004"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00049-06"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.6.1236"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.16.4.790-796.1975"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.13.6154-6165.2001"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/30.2.429"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.2002.1669"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.18.9585-9591.2004"},{"key":"e_1_3_2_41_2","first-page":"192","year":"1983","unstructured":"Mahy, B. W. J. 1983. Mutants of influenza virus, p. 192-254. In P. Palese and D. W. Kingsbury (ed.), Genetics of influenza viruses. Springer-Verlag, Vienna, Austria.","journal-title":"Genetics of influenza viruses"},{"key":"e_1_3_2_42_2","first-page":"379","year":"1981","unstructured":"Mahy, B. W. J., T. Barrett, S. T. Nichol, C. R. Penn, and A. J. Wolstenholme. 1981. Analysis of the functions of influenza virus genome RNA segments by use of temperature sensitive mutants of fowl plague virus, p. 379-387. In D. H. L. Bishop and R. W. Compans (ed.), The replication of negative stranded viruses. Elsevier North Holland, Inc., New York, NY.","journal-title":"The replication of negative stranded viruses"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(91)90883-D"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/0168-1702(89)90058-0"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90576-K"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.65.1.232-244.1991"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00627-06"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.6.3595-3605.2005"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.9.7349-7356.1999"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2007.07.007"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.80518-0"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.08-112110"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.82809-0"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.39.22701"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02655-06"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2003.12.022"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-83-4-723"},{"key":"e_1_3_2_58_2","first-page":"69","volume":"3","year":"1985","unstructured":"Ruigrok, R. W., P. C. Krijgsman, F. M. de Ronde-Verloop, and J. C. de Jong. 1985. Natural heterogeneity of shape, infectivity and protein composition in an influenza A (H3N2) virus preparation. Virus Res.3:69-76.","journal-title":"Virus Res."},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-10-1-11"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(75)90457-2"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(72)90251-6"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.62.7.2285-2290.1988"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.2002.1595"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/10.9.2925"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/0168-1702(84)90053-4"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.17.9568-9572.2004"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2008.01.009"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)38570-9"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05379"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.9.7467-7473.1999"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1996.0599"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.2000.0228"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.33.2.583-586.1980"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.01424-08","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.01424-08","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T12:44:21Z","timestamp":1646484261000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.01424-08"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,1,15]]},"references-count":72,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2009,1,15]]}},"alternative-id":["10.1128\/JVI.01424-08"],"URL":"https:\/\/doi.org\/10.1128\/jvi.01424-08","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,1,15]]},"assertion":[{"value":"2008-07-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-10-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-01-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}