{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T23:00:00Z","timestamp":1791932400748,"version":"4.3.4"},"reference-count":60,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2017,3,15]],"date-time":"2017-03-15T00:00:00Z","timestamp":1489536000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"NIH","award":["RO1 CA161048"],"award-info":[{"award-number":["RO1 CA161048"]}]},{"name":"NIH","award":["CA188359"],"award-info":[{"award-number":["CA188359"]}]},{"name":"NIH","award":["CA175577"],"award-info":[{"award-number":["CA175577"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2017,3,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>Recombinant vesicular stomatitis virus (VSV)-based chimeric viruses that include genes from other viruses show promise as vaccines and oncolytic viruses. However, the critical safety concern is the neurotropic nature conveyed by the VSV glycoprotein. VSVs that include the VSV glycoprotein (G) gene, even in most recombinant attenuated strains, can still show substantial adverse or lethal actions in the brain. Here, we test 4 chimeric viruses in the brain, including those in which glycoprotein genes from Nipah, chikungunya (CHIKV), and influenza H5N1 viruses were substituted for the VSV glycoprotein gene. We also test a virus-like vesicle (VLV) in which the VSV glycoprotein gene is expressed from a replicon encoding the nonstructural proteins of Semliki Forest virus. VSV\u0394G-CHIKV, VSV\u0394G-H5N1, and VLV were all safe in the adult mouse brain, as were VSV\u0394G viruses expressing either the Nipah F or G glycoprotein. In contrast, a complementing pair of VSV\u0394G viruses expressing Nipah G and F glycoproteins were lethal within the brain within a surprisingly short time frame of 2 days. Intranasal inoculation in postnatal day 14 mice with VSV\u0394G-CHIKV or VLV evoked no adverse response, whereas VSV\u0394G-H5N1 by this route was lethal in most mice. A key immune mechanism underlying the safety of VSV\u0394G-CHIKV, VSV\u0394G-H5N1, and VLV in the adult brain was the type I interferon response; all three viruses were lethal in the brains of adult mice lacking the interferon receptor, suggesting that the viruses can infect and replicate and spread in brain cells if not blocked by interferon-stimulated genes within the brain.<\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Vesicular stomatitis virus (VSV) shows considerable promise both as a vaccine vector and as an oncolytic virus. The greatest limitation of VSV is that it is highly neurotropic and can be lethal within the brain. The neurotropism can be mostly attributed to the VSV G glycoprotein. Here, we test 4 chimeric viruses of VSV with glycoprotein genes from Nipah, chikungunya, and influenza viruses and nonstructural genes from Semliki Forest virus. Two of the four, VSV\u0394G-CHIKV and VLV, show substantially attenuated neurotropism and were safe in the healthy adult mouse brain. VSV\u0394G-H5N1 was safe in the adult brain but lethal in the younger brain. VSV\u0394G Nipah F+G was even more neurotropic than wild-type VSV, evoking a rapid lethal response in the adult brain. These results suggest that while chimeric VSVs show promise, each must be tested with both intranasal and intracranial administration to ensure the absence of lethal neurotropism.\n          <\/jats:p>","DOI":"10.1128\/jvi.02154-16","type":"journal-article","created":{"date-parts":[[2017,1,12]],"date-time":"2017-01-12T02:32:08Z","timestamp":1484188328000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":40,"title":["Chikungunya, Influenza, Nipah, and Semliki Forest Chimeric Viruses with Vesicular Stomatitis Virus: Actions in the Brain"],"prefix":"10.1128","volume":"91","author":[{"given":"Anthony N.","family":"van den Pol","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guochao","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anasuya","family":"Chattopadhyay","sequence":"additional","affiliation":[{"name":"Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John K.","family":"Rose","sequence":"additional","affiliation":[{"name":"Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John N.","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02308-14"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00482-2"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-006-0042-3"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2008.09.031"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000225"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2008.09.082"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00561-09"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001567"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.6.4704-4711.1998"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)61117-5"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.16.8843-8856.2003"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-1013"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/77558"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(03)00241-1"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2010.216"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nov173"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.67.11.6698-6706.1993"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.3.1309-1327.2002"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01106-12"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4905-07.2008"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/cgt.2013.63"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2004.08.039"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00478-06"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.24.15043-15053.2005"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01515-07"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/cne.22131"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02040-09"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.5.3723-3732.1999"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.13.6107-6114.2001"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.10.5740-5748.2003"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01911-06"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1406035"},{"key":"e_1_3_2_34_2","first-page":"1647","volume-title":"Fields virology","author":"Palese P","year":"2007","unstructured":"Palese P Shaw ML . 2007. 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