{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,21]],"date-time":"2025-09-21T17:35:15Z","timestamp":1758476115231,"version":"3.41.2"},"reference-count":30,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2018,4,1]],"date-time":"2018-04-01T00:00:00Z","timestamp":1522540800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000052","name":"HHS | NIH | NIH Office of the Director","doi-asserted-by":"publisher","award":["AG032958"],"award-info":[{"award-number":["AG032958"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000052","name":"HHS | NIH | NIH Office of the Director","doi-asserted-by":"publisher","award":["P51RR00164"],"award-info":[{"award-number":["P51RR00164"]}],"id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Simian varicella virus (SVV), the primate counterpart of varicella-zoster virus, causes varicella (chickenpox), establishes latency in ganglia, and reactivates to produce zoster. We previously demonstrated that a recombinant SVV expressing enhanced green fluorescent protein (rSVV.eGFP) is slightly attenuated both in culture and in infected monkeys. Here, we generated two additional recombinant SVVs to visualize infected cells\n            <jats:italic>in vitro<\/jats:italic>\n            and\n            <jats:italic>in vivo<\/jats:italic>\n            . One harbors eGFP fused to the N terminus of open reading frame 9 (ORF9) (rSVV.eGFP-2a-ORF9), and another harbors eGFP fused to the C terminus of ORF66 (rSVV.eGFP-ORF66). Both recombinant viruses efficiently expressed eGFP in cultured cells. Both recombinant SVV infections in culture were comparable to that of wild-type SVV (SVV.wt). Unlike SVV.wt, eGFP-tagged SVV did not replicate in rhesus cells in culture. Intratracheal (i.t.) or i.t. plus intravenous (i.v.) inoculation of rhesus macaques with these new eGFP-tagged viruses resulted in low viremia without varicella rash, although SVV DNA was abundant in bronchoalveolar lavage (BAL) fluid at 10 days postinoculation (dpi). SVV DNA was also found in trigeminal ganglia of one monkey inoculated with rSVV.eGFP-ORF66. Intriguingly, a humoral response to both SVV and eGFP was observed. In addition, monkeys inoculated with the eGFP-expressing viruses were protected from superinfection with SVV.wt, suggesting that the monkeys had mounted an efficient immune response. Together, our results show that eGFP expression could be responsible for their reduced pathogenesis.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            SVV infection in nonhuman primates has served as an extremely useful animal model to study varicella-zoster virus (VZV) pathogenesis. eGFP-tagged viruses are a great tool to investigate their pathogenesis. We constructed and tested two new recombinant SVVs with eGFP inserted into two different locations in the SVV genome. Both recombinant SVVs showed robust replication in culture but reduced viremia compared to that with SVV.wt during primary infection in rhesus macaques. Our results indicate that conclusions on eGFP-tagged viruses based on\n            <jats:italic>in vitro<\/jats:italic>\n            results should be handled with care, since eGFP expression could result in attenuation of the virus.\n          <\/jats:p>","DOI":"10.1128\/jvi.02253-17","type":"journal-article","created":{"date-parts":[[2018,1,12]],"date-time":"2018-01-12T11:10:25Z","timestamp":1515755425000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["Attenuation of Simian Varicella Virus Infection by Enhanced Green Fluorescent Protein in Rhesus Macaques"],"prefix":"10.1128","volume":"92","author":[{"given":"Ravi","family":"Mahalingam","sequence":"first","affiliation":[{"name":"Department of Neurology, University of Colorado School of Medicine, Aurora, Colorado, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benedikt B.","family":"Kaufer","sequence":"additional","affiliation":[{"name":"Institute for Virology, Freie Universit\u00e4t Berlin, Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Werner J. D.","family":"Ouwendijk","sequence":"additional","affiliation":[{"name":"Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georges M. G. M.","family":"Verjans","sequence":"additional","affiliation":[{"name":"Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands"},{"name":"Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine Hannover, Hannover, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin","family":"Coleman","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Colorado School of Medicine, Aurora, Colorado, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meredith","family":"Hunter","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Tulane University, Tulane National Primate Research Center, Covington, Louisiana, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arpita","family":"Das","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Tulane University, Tulane National Primate Research Center, Covington, Louisiana, 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