{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T02:27:46Z","timestamp":1791080866374,"version":"4.1.0"},"reference-count":37,"publisher":"American Society for Microbiology","issue":"24","license":[{"start":{"date-parts":[[2008,12,15]],"date-time":"2008-12-15T00:00:00Z","timestamp":1229299200000},"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":[[2008,12,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>A molecular clone of yellow fever virus (YFV) strain 17D was used to identify critical determinants of mouse neuroinvasiveness previously localized to domain III of the neuroadapted SPYF-MN virus envelope protein. Three candidate virulence substitutions (305F\u2192V, 326K\u2192E, and 380R\u2192T) were individually evaluated for their roles in this phenotype in a SCID mouse model. The virus containing a glutamic acid residue at position 326 of the envelope protein (326E) caused rapidly lethal encephalitis, with a mortality rate and average survival time resembling those of the parental SPYF-MN virus. Determinants at positions 380 (380T) and 305 (305V) did not independently affect neuroinvasiveness. Testing a panel of viruses with various amino acid substitutions at position 326 revealed that attenuation of neuroinvasiveness required a positively charged residue (lysine or arginine) at this position. Molecular-modeling studies suggest that residues 326 and 380 contribute to charge clusters on the lateral surface of domain III that constitute putative heparin binding sites, as confirmed by studies of heparin inhibition of plaque formation. The neuroinvasiveness of YFVs in the SCID model correlated inversely with sensitivity to heparin. These findings establish that residue 326 in domain III of the E protein is a critical determinant of YFV neuroinvasiveness in the SCID mouse model. Together with modeling of domain III from virulent YFV strains, the data suggest that heparin binding activity involving lysine at position 326 may be a modulator of YFV virulence phenotypes.<\/jats:p>","DOI":"10.1128\/jvi.00458-08","type":"journal-article","created":{"date-parts":[[2008,10,9]],"date-time":"2008-10-09T00:44:50Z","timestamp":1223513090000},"page":"12510-12519","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":22,"title":["Neuroadapted Yellow Fever Virus Strain 17D: a Charged Locus in Domain III of the E Protein Governs Heparin Binding Activity and Neuroinvasiveness in the SCID Mouse Model"],"prefix":"10.1128","volume":"82","author":[{"given":"Janice","family":"Nickells","sequence":"first","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Doisy Research Center, St. Louis University School of Medicine, 1100 South Grand Boulevard, St. Louis, Missouri 63104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Cannella","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Doisy Research Center, St. Louis University School of Medicine, 1100 South Grand Boulevard, St. Louis, Missouri 63104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah A.","family":"Droll","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Doisy Research Center, St. Louis University School of Medicine, 1100 South Grand Boulevard, St. Louis, Missouri 63104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Doisy Research Center, St. Louis University School of Medicine, 1100 South Grand Boulevard, St. Louis, Missouri 63104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William S. M.","family":"Wold","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Doisy Research Center, St. Louis University School of Medicine, 1100 South Grand Boulevard, St. Louis, Missouri 63104"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Chambers","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Doisy Research Center, St. Louis University School of Medicine, 1100 South Grand Boulevard, St. Louis, Missouri 63104"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.7.5605-5612.1999"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-67-4-631"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.22.10912-10922.2001"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-3527(03)60008-4"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.6.3655-3668.2003"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0897-866"},{"key":"e_1_3_2_8_2","first-page":"80","volume":"11","year":"1959","unstructured":"Collier, W. A., H. De Roever-Bonnet, and J. Hoekstra. 1959. A neurotropic variety of the vaccine strain 17D. Trop. Geogr. Med.11:80.","journal-title":"Trop. Geogr. Med."},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-46-1-1"},{"key":"e_1_3_2_10_2","first-page":"741","year":"1994","unstructured":"Freestone, D. S. 1994. Yellow fever vaccine, p. 741-779. In S. A. Plotkin and E. M. Mortimer (ed.), Vaccines, 2nd ed. W. B. Saunders, Philadelphia, PA.","journal-title":"Vaccines"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.2001.1232"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(92)90177-Q"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1521-1878(199802)20:2<156::AID-BIES8>3.0.CO;2-R"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/169.3.512"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.10.4901-4911.2002"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.15.8271-8280.2004"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.82164-0"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02509-07"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-56-2-363"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(90)90029-Q"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.20.9601-9609.2000"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.12.5627-5637.2001"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1995.1374"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-77-9-2085"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-78-11-2711"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/0035-9203(59)90020-3"},{"key":"e_1_3_2_27_2","first-page":"375","year":"1986","unstructured":"Monath, T. P. 1986. Pathobiology of the flaviviruses, p. 375-440. In S. Schlesinger and M. J. Schlesinger (ed.), The Togaviridae and the Flaviviridae. Plenum Press, New York, NY.","journal-title":"The Togaviridae and the Flaviviridae."},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1997.8956"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.6.2903-2906.2000"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.22.12232-12242.2003"},{"key":"e_1_3_2_31_2","first-page":"285","volume":"1","year":"1989","unstructured":"Rice, C. M., A. Grakoui, R. Galler, and T. J. Chambers. 1989. Transcription of infectious yellow fever virus RNA from full-length cDNA templates produced by in vitro ligation. New Biol.1:285-296.","journal-title":"New Biol."},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1997.8496"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1998.9057"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-77-6-1277"},{"key":"e_1_3_2_35_2","first-page":"83","year":"1980","unstructured":"Schlesinger, R. W. 1980. Virus-host interactions in natural and experimental infections with alphaviruses and flaviviruses, p. 83-104. In R. W. Schlesinger (ed.), The togaviruses. Academic Press, New York, NY.","journal-title":"The togaviruses."},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.11.8142-8147.1996"},{"key":"e_1_3_2_37_2","first-page":"46","year":"1951","unstructured":"Theiler, M. 1951. The virus, p. 46-136. In G. K. Strode (ed.), Yellow fever. McGraw-Hill, New York, NY.","journal-title":"Yellow fever."},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.12.6172-6184.2002"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00458-08","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.00458-08","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T12:12:33Z","timestamp":1646482353000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.00458-08"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,12,15]]},"references-count":37,"journal-issue":{"issue":"24","published-print":{"date-parts":[[2008,12,15]]}},"alternative-id":["10.1128\/JVI.00458-08"],"URL":"https:\/\/doi.org\/10.1128\/jvi.00458-08","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,12,15]]},"assertion":[{"value":"2008-03-02","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-09-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-12-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}