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HSV-2 has significantly higher<jats:italic>vhs<\/jats:italic>activity than HSV-1, eliciting a faster and more complete shutoff. To examine further the role of<jats:italic>vhs<\/jats:italic>activity in pathogenesis, we generated an intertypic recombinant virus (KOSV2) in which the<jats:italic>vhs<\/jats:italic>open reading frame of HSV-1 strain KOS was replaced with that of HSV-2 strain 333. KOSV2 and a marker-rescued virus, KOSV2R, were characterized in cell culture and tested in an in vivo mouse eye model of latency and pathogenesis. The RNA degradation kinetics of KOSV2 was identical to that of HSV-2 333, and both showed<jats:italic>vhs<\/jats:italic>activity significantly higher than that of KOS. This demonstrated that the fast<jats:italic>vhs<\/jats:italic>-mediated degradation phenotype of 333 had been conferred upon KOS. The growth of KOSV2 was comparable to that of KOS, 333, and KOSV2R in cell culture, murine corneas, and trigeminal ganglia and had a reactivation frequency similar to those of KOS and KOSV2R from explanted latently infected trigeminal ganglia. There was, however, significantly reduced blepharitis and viral replication within the periocular skin of KOSV2-infected mice compared to mice infected with either KOS or KOSV2R. Taken together, these data demonstrate that heightened<jats:italic>vhs<\/jats:italic>activity, in the context of HSV-1 infection, leads to increased viral clearance from the skin of mice and that the replication of virus in the skin is a determining factor for blepharitis. These data also suggest a role for<jats:italic>vhs<\/jats:italic>in modulating host responses to HSV infection.<\/jats:p>","DOI":"10.1128\/jvi.74.8.3598-3604.2000","type":"journal-article","created":{"date-parts":[[2002,7,27]],"date-time":"2002-07-27T10:06:37Z","timestamp":1027764397000},"page":"3598-3604","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":47,"title":["Herpes Simplex Virus Virion Host Shutoff (<i>vhs<\/i>) Activity Alters Periocular Disease in Mice"],"prefix":"10.1128","volume":"74","author":[{"given":"Tracy J.","family":"Smith","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Departments of Ophthalmology and Visual Sciences1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cathleen E.","family":"Ackland-Berglund","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Departments of Ophthalmology and Visual Sciences1 and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David A.","family":"Leib","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Departments of Ophthalmology and Visual Sciences1 and"},{"name":"<!--label omitted: 2-->Molecular Microbiology,2 Washington University School of Medicine, St. Louis, Missouri 63110"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/166.6.1401"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.65.6.3185-3191.1991"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1006\/viro.1993.1221"},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"3964","DOI":"10.4049\/jimmunol.155.8.3964","article-title":"Characterization of herpes simplex virus type-1 infection and herpetic stromal keratitis development in IFN-gamma knockout mice","volume":"155","author":"Bouley D. 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