{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T20:54:02Z","timestamp":1760820842770,"version":"3.37.3"},"reference-count":58,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2016,10,30]],"date-time":"2016-10-30T00:00:00Z","timestamp":1477785600000},"content-version":"vor","delay-in-days":29,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["Number: SAF2010\u201022106"],"award-info":[{"award-number":["Number: SAF2010\u201022106"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Although herpes simplex virus type 1 (HSV\u20101) has outstanding properties for gene delivery vectors and its genome is available in bacterial artificial chromosomes (BACs) for mutagenesis studies, one impediment is the presence of approximately 15.4\u00a0kb of DNA sequences that are duplicated in the HSV\u20101 genome, complicating vector construction and stability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>As a useful platform for building HSV\u20101 vectors, we have constructed a fully haploid HSV\u20101 genome BAC by deletion of one of these repeats, confirming that viral propagation in culture is not impaired. We used this \u0394IR mutant to subsequently investigate whether the insertion of tetracycline\u2010responsive tetO elements into the <jats:italic>ICP34.5<\/jats:italic>\u2013<jats:italic>ICP0<\/jats:italic> gene region can be used to control HSV\u20101 lytic replication.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The results of the present study show that \u0394IR mutants deleted for <jats:italic>ICP34.5<\/jats:italic> are viable for replication but not when the <jats:italic>ICP0<\/jats:italic> promoter is also disrupted, thus indicating that regulation of infected cell protein 0 (ICP0) levels in the absence of ICP34.5 could be a viable means for controlling growth of HSV\u20101 vectors. Surprisingly, however, the tetO elements inserted into the <jats:italic>ICP0<\/jats:italic> promoter did not confer ligand responsiveness to growth or ICP0 expression. Further analysis by transfection experiments revealed that ICP0 itself interferes with the tetracycline switch and reduces the the inducibility of this system.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our new haploid HSV\u20101 BAC is a useful platform for building multiply deleted HSV\u20101 vectors. Deletion of the gene for ICP34.5 in this backbone renders viral growth dependent on ICP0, although ICP0 expression could not be regulated by tet\u2010responsive transcriptional regulators.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.2929","type":"journal-article","created":{"date-parts":[[2016,9,27]],"date-time":"2016-09-27T17:42:59Z","timestamp":1474998179000},"page":"302-311","source":"Crossref","is-referenced-by-count":3,"title":["A haploid HSV\u20101 genome platform for vector development: testing of the tetracycline\u2010responsive switch shows interference by infected cell protein 0"],"prefix":"10.1002","volume":"18","author":[{"given":"Hena","family":"Khalique","sequence":"first","affiliation":[{"name":"Departamento de Biolog\u00eda Molecular Universidad Aut\u00f3noma de Madrid  Cantoblanco Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge","family":"L\u00f3pez Marco","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Molecular Universidad Aut\u00f3noma de Madrid  Cantoblanco Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6570-1017","authenticated-orcid":false,"given":"Filip","family":"Lim","sequence":"additional","affiliation":[{"name":"Departamento de Biolog\u00eda Molecular Universidad Aut\u00f3noma de Madrid  Cantoblanco Madrid 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