{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T06:51:18Z","timestamp":1770015078764,"version":"3.49.0"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2014,7,1]],"date-time":"2014-07-01T00:00:00Z","timestamp":1404172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2014,8,29]],"date-time":"2014-08-29T00:00:00Z","timestamp":1409270400000},"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":["mBio"],"published-print":{"date-parts":[[2014,8,29]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The catalytic site of the HIV integrase is contained within an RNase H-like fold, and numerous drugs have been developed that bind to this site and inhibit its activity. Herpes simplex virus (HSV) encodes two proteins with potential RNase H-like folds, the infected cell protein 8 (ICP8) DNA-binding protein, which is necessary for viral DNA replication and exhibits recombinase activity\n            <jats:italic>in vitro<\/jats:italic>\n            , and the viral terminase, which is essential for viral DNA cleavage and packaging. Therefore, we hypothesized that HIV integrase inhibitors might also inhibit HSV replication by targeting ICP8 and\/or the terminase. To test this, we evaluated the effect of 118-D-24, a potent HIV integrase inhibitor, on HSV replication. We found that 118-D-24 inhibited HSV-1 replication in cell culture at submillimolar concentrations. To identify more potent inhibitors of HSV replication, we screened a panel of integrase inhibitors, and one compound with greater anti-HSV-1 activity, XZ45, was chosen for further analysis. XZ45 significantly inhibited HSV-1 and HSV-2 replication in different cell types, with 50% inhibitory concentrations that were approximately 1\u00a0\u00b5M, but exhibited low cytotoxicity, with a 50% cytotoxic concentration greater than 500\u00a0\u00b5M. XZ45 blocked HSV viral DNA replication and late gene expression. XZ45 also inhibited viral recombination in infected cells and ICP8 recombinase activity\n            <jats:italic>in vitro<\/jats:italic>\n            . Furthermore, XZ45 inhibited human cytomegalovirus replication and induction of Kaposi\u2019s sarcoma herpesvirus from latent infection. Our results argue that inhibitors of enzymes with RNase H-like folds may represent a general antiviral strategy, which is useful not only against HIV but also against herpesviruses.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            The herpesviruses cause considerable morbidity and mortality. Nucleoside analogs have served as effective antiviral agents against the herpesviruses, but resistance can arise through viral mutation. Second-line anti-herpes drugs have limitations in terms of pharmacokinetic properties and\/or toxicity, so there is a great need for additional drugs for treatment of herpesviral infections. This study showed that the HIV integrase inhibitors also block herpesviral infection, raising the important potential of a new class of anti-herpes drugs and the prospect of drugs that combat both HIV and the herpesviruses.\n          <\/jats:p>","DOI":"10.1128\/mbio.01318-14","type":"journal-article","created":{"date-parts":[[2014,7,2]],"date-time":"2014-07-02T10:14:46Z","timestamp":1404296086000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":29,"title":["HIV Integrase Inhibitors Block Replication of Alpha-, Beta-, and Gammaherpesviruses"],"prefix":"10.1128","volume":"5","author":[{"given":"Zhipeng","family":"Yan","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin F.","family":"Bryant","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean M.","family":"Gregory","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magdalena","family":"Angelova","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David H.","family":"Dreyfus","sequence":"additional","affiliation":[{"name":"Allergy and Clinical Immunology\/Pediatrics, Yale School of Medicine, New Haven, Connecticut, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue Zhi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Chemical Biology Laboratory, Frederick National Laboratory for Cancer Research, Center for Cancer Research, National Cancer Institute\u2014Frederick, National Institutes of Health, Frederick, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donald M.","family":"Coen","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr.","given":"Terrence R.","family":"Burke","sequence":"additional","affiliation":[{"name":"Chemical Biology Laboratory, Frederick National Laboratory for Cancer Research, Center for Cancer Research, National Cancer Institute\u2014Frederick, National Institutes of Health, Frederick, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M.","family":"Knipe","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","first-page":"1823","volume-title":"Fields virology","author":"Roizman B","year":"2013","unstructured":"RoizmanB KnipeDM WhitleyRJ . 2013. 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