{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T14:18:20Z","timestamp":1790259500213,"version":"4.1.0"},"reference-count":78,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2012,5,15]],"date-time":"2012-05-15T00:00:00Z","timestamp":1337040000000},"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":[[2012,5,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            PB1-F2 is an 87- to 90-amino-acid-long protein expressed by certain influenza A viruses. Previous studies have shown that PB1-F2 contributes to virulence in the mouse model; however, its role in natural hosts\u2014pigs, humans, or birds\u2014remains largely unknown. Outbreaks of domestic pigs infected with the 2009 pandemic H1N1 influenza virus (pH1N1) have been detected worldwide. Unlike previous pandemic strains, pH1N1 viruses do not encode a functional PB1-F2 due to the presence of three stop codons resulting in premature truncation after codon 11. However, pH1N1s have the potential to acquire the full-length form of PB1-F2 through mutation or reassortment. In this study, we assessed whether restoring the full-length PB1-F2 open reading frame (ORF) in the pH1N1 background would have an effect on virus replication and virulence in pigs. Restoring the PB1-F2 ORF resulted in upregulation of viral polymerase activity at early time points\n            <jats:italic>in vitro<\/jats:italic>\n            and enhanced virus yields in porcine respiratory explants and in the lungs of infected pigs. There was an increase in the severity of pneumonia in pigs infected with isogenic virus expressing PB1-F2 compared to the wild-type (WT) pH1N1. The extent of microscopic pneumonia correlated with increased pulmonary levels of alpha interferon and interleukin-1\u03b2 in pigs infected with pH1N1 encoding a functional PB1-F2 but only early in the infection. Together, our results indicate that PB1-F2 in the context of pH1N1 moderately modulates viral replication, lung histopathology, and local cytokine response in pigs.\n          <\/jats:p>","DOI":"10.1128\/jvi.00134-12","type":"journal-article","created":{"date-parts":[[2012,3,1]],"date-time":"2012-03-01T02:41:17Z","timestamp":1330569677000},"page":"5523-5532","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":34,"title":["Restored PB1-F2 in the 2009 Pandemic H1N1 Influenza Virus Has Minimal Effects in Swine"],"prefix":"10.1128","volume":"86","author":[{"given":"Lindomar","family":"Pena","sequence":"first","affiliation":[{"name":"Department of Veterinary Medicine, University of Maryland College Park and Virginia-Maryland Regional College of Veterinary Medicine, College Park, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy L.","family":"Vincent","sequence":"additional","affiliation":[{"name":"Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA-ARS, Ames, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crystal L.","family":"Loving","sequence":"additional","affiliation":[{"name":"Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA-ARS, Ames, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie N.","family":"Henningson","sequence":"additional","affiliation":[{"name":"Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA-ARS, Ames, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly M.","family":"Lager","sequence":"additional","affiliation":[{"name":"Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA-ARS, Ames, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Lorusso","sequence":"additional","affiliation":[{"name":"Virus and Prion Diseases of Livestock Research Unit, National Animal Disease Center, USDA-ARS, Ames, Iowa, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel R.","family":"Perez","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Maryland College Park and Virginia-Maryland Regional College of Veterinary Medicine, College Park, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.5144\/0256-4947.59365"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2008.12.014"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2008.04.006"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1606.100352"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1089\/vim.2008.0075"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1136\/vr.164.24.760"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.091087"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00592-10"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2007.04.017"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1201-1306"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2007.09.010"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0030141"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0903810"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1612.100514"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1176225"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2011.01.082"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422X-6-207"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00879-10"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02717-09"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1177\/030098589503200606"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.2008\/004606-0"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1062882"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI1355"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.100133697"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.2807\/ese.14.45.19406-en"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid\/1706.101886"},{"key":"e_1_3_2_28_2","first-page":"1153","article-title":"An investigation into human pandemic influenza virus (H1N1) 2009 on an Alberta swine farm","volume":"50","author":"Howden KJ","year":"2009","unstructured":"HowdenKJ . 2009. An investigation into human pandemic influenza virus (H1N1) 2009 on an Alberta swine farm. Can. Vet. J. 50:1153\u20131161.","journal-title":"Can. Vet. J."},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.9.7367-7373.1998"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08260"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-75-9-2183"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422X-7-365"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.014480-0"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903952"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2010.06.004"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.05705-11"},{"key":"e_1_3_2_37_2","first-page":"60","article-title":"Experimental reproduction of clinical disease by intratracheal inoculation of fattening pigs with swine influenza virus isolates","volume":"8","author":"Maes L","year":"1984","unstructured":"MaesL HaesebrouckF PensaertM. 1984. Experimental reproduction of clinical disease by intratracheal inoculation of fattening pigs with swine influenza virus isolates. Proc. Int. Congr. Pig Vet. Soc. 8:60.","journal-title":"Proc. Int. Congr. Pig Vet. Soc."},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1604.091402"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2008.01116.x"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001014"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2007.09.001"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01785-09"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2010.12.011"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1086\/512813"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1186\/1746-6148-6-4"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1409.080305"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1507.081574"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00029-11"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0711815105"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01503-10"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1602.091230"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-2659.2011.00246.x"},{"key":"e_1_3_2_53_2","first-page":"493","article-title":"A simple method for estimating 50 percent endpoints","volume":"37","author":"Reed LJ","year":"1938","unstructured":"ReedLJ MuenchH. 1938. A simple method for estimating 50 percent endpoints. Am. J. Hyg. 37:493.","journal-title":"Am. J. Hyg."},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.009639-0"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1312.070615"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1038\/440435a"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1001081"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08182"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00053-10"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1603.091737"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.028662-0"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1177\/104063871002200525"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2010.05.009"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1371\/currents.RRN1006"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI44947"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422X-7-38"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1135(00)00171-1"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1053\/rvsc.1998.0277"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1089\/088282402320914520"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1189132"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-2659.2009.00121.x"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetmic.2009.01.003"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1177\/104063879700900214"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2005.10.035"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0806959106"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02399-08"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001145"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00415-06"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.82378-0"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00134-12","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00134-12","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T15:12:59Z","timestamp":1646493179000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.00134-12"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,5,15]]},"references-count":78,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2012,5,15]]}},"alternative-id":["10.1128\/JVI.00134-12"],"URL":"https:\/\/doi.org\/10.1128\/jvi.00134-12","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,5,15]]},"assertion":[{"value":"2012-01-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-02-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-04-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}