{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:43:20Z","timestamp":1791315800149,"version":"4.3.1"},"reference-count":66,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2015,2,10]],"date-time":"2015-02-10T00:00:00Z","timestamp":1423526400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2015,2,27]],"date-time":"2015-02-27T00:00:00Z","timestamp":1424995200000},"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":["mBio"],"published-print":{"date-parts":[[2015,2,27]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>Paramyxoviruses, including the human pathogen measles virus (MV), enter host cells by fusing their viral envelope with the target cell membrane. This fusion process is driven by the concerted actions of the two viral envelope glycoproteins, the receptor binding protein (hemagglutinin [H]) and the fusion (F) protein. H attaches to specific proteinaceous receptors on host cells; once the receptor engages, H activates F to directly mediate lipid bilayer fusion during entry. In a recent MV outbreak in South Africa, several HIV-positive people died of MV central nervous system (CNS) infection. We analyzed the virus sequences from these patients and found that specific intrahost evolution of the F protein had occurred and resulted in viruses that are \u201cCNS adapted.\u201d A mutation in F of the CNS-adapted virus (a leucine-to-tryptophan change present at position 454) allows it to promote fusion with less dependence on engagement of H by the two known wild-type (wt) MV cellular receptors. This F protein is activated independently of H or the receptor and has reduced thermal stability and increased fusion activity compared to those of the corresponding wt F. These functional effects are the result of the single L454W mutation in F. We hypothesize that in the absence of effective cellular immunity, such as HIV infection, MV variants bearing altered fusion machinery that enabled efficient spread in the CNS underwent positive selection.<\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Measles virus has become a concern in the United States and Europe due to recent outbreaks and continues to be a significant global problem. While live immunization is available, there are no effective therapies or prophylactics to combat measles infection in unprotected people. Additionally, vaccination does not adequately protect immunocompromised people, who are vulnerable to the more severe CNS manifestations of disease. We found that strains isolated from patients with measles virus infection of the CNS have fusion properties different from those of strains previously isolated from patients without CNS involvement. Specifically, the viral entry machinery is more active and the virus can spread, even in the absence of H. Our findings are consistent with an intrahost evolution of the fusion machinery that leads to neuropathogenic MV variants.\n          <\/jats:p>","DOI":"10.1128\/mbio.02528-14","type":"journal-article","created":{"date-parts":[[2015,2,11]],"date-time":"2015-02-11T02:38:28Z","timestamp":1423622308000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":56,"title":["Measles Fusion Machinery Is Dysregulated in Neuropathogenic Variants"],"prefix":"10.1128","volume":"6","author":[{"given":"Eric M.","family":"Jurgens","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Weill Medical College of Cornell University, Ithaca, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyrille","family":"Mathieu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Weill Medical College of Cornell University, Ithaca, New York, USA"},{"name":"CIRI (International Center for Research in Infectiology), Lyon, France"},{"name":"INSERM U1111, Lyon, France"},{"name":"CNRS, UMR5308, Lyon, France"},{"name":"Universit\u00e9 Lyon 1, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura M.","family":"Palermo","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Hardie","sequence":"additional","affiliation":[{"name":"Division of Medical Virology, Department of Clinical Laboratory Sciences, University of Cape Town, and National Health Laboratory Service, Cape Town, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Branka","family":"Horvat","sequence":"additional","affiliation":[{"name":"CIRI (International Center for Research in Infectiology), Lyon, France"},{"name":"INSERM U1111, Lyon, France"},{"name":"CNRS, UMR5308, Lyon, France"},{"name":"Universit\u00e9 Lyon 1, Lyon, France"},{"name":"Ecole Normale Sup\u00e9rieure de Lyon, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Moscona","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Weill Medical College of Cornell University, Ithaca, New York, USA"},{"name":"Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Porotto","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Weill Medical College of Cornell University, Ithaca, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)62352-5"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/377696"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1086\/377713"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60522-4"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2012.03.005"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01559-09"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12025"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001263"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.06414-11"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature10639"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2012.00330.x"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1211138109"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.2.5420.1296"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1959.03010260006002"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0361-9230(97)00139-1"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2011.00247"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.1969"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002240"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nsmb.1456"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.3390\/v4040613"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1080\/10409230802058320"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2007.12.008"},{"key":"e_1_3_3_24_2","doi-asserted-by":"crossref","unstructured":"Young VA Rall GF. 2009. Making it to the synapse: measles virus spread in and among neurons. Curr Top Microbiol Immunol 330:3\u201330. doi:10.1007\/978-3-540-70617-5_1.","DOI":"10.1007\/978-3-540-70617-5_1"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02632-12"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-010-9200-4"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2007.02.033"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01965-14"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00803-13"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422X-10-283"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid1211.060635"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.21.11546-11554.2003"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.14.6643-6647.2000"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01646-13"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02256-13"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coviro.2014.01.004"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01210-13"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.2.921-933.2001"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2014.05.035"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.49.9.3755-3761.2005"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02632-12"},{"key":"e_1_3_3_42_2","doi-asserted-by":"crossref","unstructured":"Moscona A Peluso RW. 1993. Relative affinity of the human parainfluenza virus type 3 hemagglutinin-neuraminidase for sialic acid correlates with virus-induced fusion activity. J Virol 67:6463\u20136468.","DOI":"10.1128\/jvi.67.11.6463-6468.1993"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.06793-11"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01965-12"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.23.11108-11114.2000"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.15.4024"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.298059"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01826-12"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02436-13"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2005.04.005"},{"key":"e_1_3_3_51_2","doi-asserted-by":"crossref","unstructured":"Cattaneo R Schmid A Billeter MA Sheppard RD Udem SA. 1988. Multiple viral mutations rather than host factors cause defective measles virus gene expression in a subacute sclerosing panencephalitis cell line. J Virol 62:1388\u20131397.","DOI":"10.1128\/jvi.62.4.1388-1397.1988"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-53488-0.00027-4"},{"key":"e_1_3_3_53_2","doi-asserted-by":"crossref","unstructured":"Fisher DL Defres S Solomon T. May 2014. Measles-induced encephalitis. QJM doi:10.1093\/qjmed\/hcu113.","DOI":"10.1093\/qjmed\/hcu113"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-7020-4088-7.00091-2"},{"key":"e_1_3_3_55_2","doi-asserted-by":"crossref","unstructured":"Albertyn C van der Plas H Hardie D Candy S Tomoka T Leepan EB Heckmann JM. 2011. Silent casualties from the measles outbreak in South Africa. S Afr Med J 101:313\u2013314 316\u2013317.","DOI":"10.7196\/SAMJ.4616"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.05873-11"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00413-13"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.03123-13"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/205617"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI35454"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00475-09"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02617-06"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/24.6.1171"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001168"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.13.6743-6749.2002"},{"key":"e_1_3_3_66_2","doi-asserted-by":"crossref","unstructured":"Radecke F Spielhofer P Schneider H Kaelin K Huber M D\u00f6tsch C Christiansen G Billeter MA. 1995. Rescue of measles viruses from cloned DNA. EMBO J 14:5773\u20135784.","DOI":"10.1002\/j.1460-2075.1995.tb00266.x"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02417-14"}],"container-title":["mBio"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.02528-14","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/mBio.02528-14","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T02:02:49Z","timestamp":1646704969000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/mBio.02528-14"}},"subtitle":[],"editor":[{"given":"Terence S.","family":"Dermody","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2015,2,27]]},"references-count":66,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015,2,27]]}},"alternative-id":["10.1128\/mBio.02528-14"],"URL":"https:\/\/doi.org\/10.1128\/mbio.02528-14","relation":{},"ISSN":["2161-2129","2150-7511"],"issn-type":[{"value":"2161-2129","type":"print"},{"value":"2150-7511","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,2,27]]},"assertion":[{"value":"2014-12-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-12-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-02-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e02528-14"}}