{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T07:44:45Z","timestamp":1764402285082},"reference-count":43,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2003,1,1]],"date-time":"2003-01-01T00:00:00Z","timestamp":1041379200000},"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":[[2003,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Varicella-zoster virus (VZV) glycoprotein I is dispensable in cell culture but necessary for infection of human skin and T cells in SCIDhu mice in vivo. The gI promoter contains an activating upstream sequence that binds the cellular transactivators specificity factor 1 (Sp1) and upstream stimulatory factor (USF) and an open reading frame 29 (ORF29)-responsive element (29RE), which mediates enhancement by ORF29 DNA binding protein of immediate-early 62 (IE62)-induced transcription. Recombinants, rOKAgI-Sp1 and rOKAgI-USF, with two base pair substitutions in Sp1 or USF sites, replicated like rOKA in vitro, but infectivity of rOKAgI-Sp1 was significantly impaired in skin and T cells in vivo. A double mutant, rOKAgI-Sp1\/USF, did not replicate in skin but yielded low titers of infectious virus in T cells. The repaired protein, rOKAgI:rep-Sp1\/USF, was as infectious as rOKA. Thus, disrupting gI promoter sites for cellular transactivators altered VZV virulence in vivo, with variable consequences related to the cellular factor and the host cell type. Mutations in the 29RE of the gI promoter were made by substituting each of four 10-bp blocks in this region with a 10-bp sequence, GATAACTACA, that was predicted to interfere with enhancer effects of the ORF29 protein. One of these mutants, which was designated rOKAgI-29RE-3, had diminished replication in skin and T cells, indicating that ORF29 protein-mediated enhancement of gI expression contributes to VZV virulence. Mutations within promoters of viral genes that are nonessential in vitro should allow construction of recombinant herpesviruses that have altered virulence in specific host cells in vivo and may be useful for designing herpesviral gene therapy vectors and attenuated viral vaccines.<\/jats:p>","DOI":"10.1128\/jvi.77.1.489-498.2003","type":"journal-article","created":{"date-parts":[[2002,12,11]],"date-time":"2002-12-11T19:22:58Z","timestamp":1039634578000},"page":"489-498","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":49,"title":["Promoter Sequences of Varicella-Zoster Virus Glycoprotein I Targeted by Cellular Transactivating Factors Sp1 and USF Determine Virulence in Skin and T Cells in SCIDhu Mice In Vivo"],"prefix":"10.1128","volume":"77","author":[{"given":"Hideki","family":"Ito","sequence":"first","affiliation":[{"name":"Departments of Pediatrics"},{"name":"Microbiology and Immunology, Stanford University, Stanford, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marvin H.","family":"Sommer","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics"},{"name":"Microbiology and Immunology, Stanford University, Stanford, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leigh","family":"Zerboni","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics"},{"name":"Microbiology and Immunology, Stanford University, Stanford, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongying","family":"He","sequence":"additional","affiliation":[{"name":"Department of Microbiology, State University of New York at Buffalo, Buffalo, New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dwayne","family":"Boucaud","sequence":"additional","affiliation":[{"name":"Department of Microbiology, State University of New York at Buffalo, Buffalo, New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Hay","sequence":"additional","affiliation":[{"name":"Department of Microbiology, State University of New York at Buffalo, Buffalo, New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Ruyechan","sequence":"additional","affiliation":[{"name":"Department of Microbiology, State University of New York at Buffalo, Buffalo, New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann M.","family":"Arvin","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics"},{"name":"Microbiology and Immunology, Stanford University, Stanford, California"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.22.13430"},{"key":"e_1_3_2_3_2","first-page":"129","volume":"1072","year":"1991","unstructured":"Angel, P., K. M. 1991. The role of Jun, Fos and the AP-1 complex in cell proliferation and transformation. Biochim. Biophys. Acta 1072 : 129-157.","journal-title":"Biochim. Biophys. Acta"},{"key":"e_1_3_2_4_2","doi-asserted-by":"crossref","unstructured":"Arvin A. M. 2001. Varicella-zoster virus p. 2731-2768. In D. N. Knipe P. M. Howley et al. (ed.) Fields virology 4th ed. vol. 2. Lippincott Williams & Wilkins Philadelphia Pa.","DOI":"10.1016\/S1369-5274(00)00233-2"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-75-6-1245"},{"key":"e_1_3_2_6_2","unstructured":"Cohen J. I. and Straus S. E. 2001. Varicella-zoster virus and its replication p. 2707-2730. In D. N. Knipe P. M. Howley et al. (ed.) Fields virology 4th ed. vol. 2. Lippincott Williams & Wilkins Philadelphia Pa."},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.9.6913-6920.1997"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.11.7087-7098.1995"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.68.10.6372-6390.1994"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.mi.44.100190.000423"},{"key":"e_1_3_2_11_2","first-page":"57","volume":"17","year":"2001","unstructured":"He, H., D. Boucaud, J. Hay, and W. T. Ruyechan. 2001. Cis and trans elements regulating expression of the varicella zoster virus gI gene. Arch. Virol. Suppl. 17 : 57-70.","journal-title":"Arch. Virol. Suppl."},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.2.821-833.2001"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.23.11311-11321.2000"},{"key":"e_1_3_2_14_2","first-page":"74","year":"2000","unstructured":"Kinchington, P. R., and J. I. Cohen. 2000. Viral proteins, p. 74-104. In A. M. Arvin and A. A. Gershon (ed.), Varicella zoster virus: virology and clonical management. Cambridge University Press, Cambridge, United Kingdom.","journal-title":"Varicella zoster virus: virology and clonical management"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-2725(97)00094-0"},{"key":"e_1_3_2_16_2","first-page":"621","volume":"2","year":"1994","unstructured":"Littlewood, T. D., E. G. 1994. Transcription factors 2: helix-loop-lelix. Protein Profile 2 : 621-702.","journal-title":"Protein Profile"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.11.8279-8288.1997"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.14.10.6896-6906.1994"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1086\/515586"},{"key":"e_1_3_2_20_2","unstructured":"Virology"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.16.8468-8471.2002"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.69.9.5236-5242.1995"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.2.965-974.1998"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.20.11969"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.2.1542-1551.1998"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.71.5.4042-4054.1997"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.66.9.5298-5304.1992"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(92)90197-W"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.2.1508"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-1702(99)00075-1"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1159\/000025044"},{"key":"e_1_3_2_32_2","unstructured":"Roizman B. and Knipe D. N. 2001. Herpes simplex viruses and their replication p. 2399-2459. In D. N. Knipe and P. M. Howley (ed.) Fields virology 4th ed. vol. 2. Lippincott-Raven Publishers Philadelphia Pa."},{"key":"e_1_3_2_33_2","first-page":"51","year":"2000","unstructured":"Ruyechan, W. T., and J. Hay. 2000. DNA replication, p. 51-73. In A. M. Arvin and A. A. Gershon (ed.), Varicella zoster virus: virology and clonical management. Cambridge University Press, Cambridge, United Kingdom.","journal-title":"Varicella zoster virus: virology and clonical management"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.239.4839.487"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.2000.0507"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.17.8224-8239.2001"},{"key":"e_1_3_2_37_2","doi-asserted-by":"crossref","unstructured":"Spear P. G. 1985. Glycoproteins specified by herpes simplex viruses p. 315-356. In B. Roizman (ed.) The herpesviruses 4th ed. vol. 3. Plenum Press New York N.Y.","DOI":"10.1007\/978-1-4613-2383-9_7"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(99)00357-1"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.8.3505-3516.2000"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.14.6600-6613.2000"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.1.323-340.2001"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.67.1.305-314.1993"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.2.1320-1330.1999"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.70.10.6563-6575.1996"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.77.1.489-498.2003","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.77.1.489-498.2003","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T16:11:57Z","timestamp":1682439117000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.77.1.489-498.2003"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,1]]},"references-count":43,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2003,1]]}},"alternative-id":["10.1128\/JVI.77.1.489-498.2003"],"URL":"https:\/\/doi.org\/10.1128\/jvi.77.1.489-498.2003","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,1]]},"assertion":[{"value":"2002-07-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-09-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2003-01-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}