{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T01:42:27Z","timestamp":1790905347705,"version":"4.1.0"},"reference-count":54,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2016,3,15]],"date-time":"2016-03-15T00:00:00Z","timestamp":1458000000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["BR 1730\/3-2"],"award-info":[{"award-number":["BR 1730\/3-2"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2016,3,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Molluscum contagiosum virus (MCV) gene\n            <jats:italic>MC159<\/jats:italic>\n            encodes a viral FLICE inhibitory protein (vFLIP) that inhibits caspase-8-mediated apoptosis. The MC159 protein was also reported to inhibit programmed necrosis (necroptosis) and modulate NF-\u03baB activation by interacting with RIP1 and NEMO. The importance of MC159 during MCV infection has remained unknown, as there is no system for propagation and genetic manipulation of this virus. Here we investigated the functions of MC159 during viral infection using murine cytomegalovirus (MCMV) as a surrogate virus.\n            <jats:italic>MC159<\/jats:italic>\n            was inserted into the MCMV genome, replacing\n            <jats:italic>M36<\/jats:italic>\n            or\n            <jats:italic>M45<\/jats:italic>\n            , two MCMV genes with functions similar to those reported for\n            <jats:italic>MC159<\/jats:italic>\n            .\n            <jats:italic>M36<\/jats:italic>\n            encodes a viral inhibitor of caspase-8-induced apoptosis (vICA) and\n            <jats:italic>M45<\/jats:italic>\n            a viral inhibitor of RIP activation (vIRA), which inhibits RIP1\/RIP3-mediated necroptosis. The M45 protein also blocks NF-\u03baB activation by interacting with NEMO. When expressed by MCMV, MC159 blocked tumor necrosis factor alpha (TNF-\u03b1)-induced apoptosis of infected cells and partially restored MCMV replication in macrophages. However, MC159 did not fully replace M45, as it did not inhibit necroptosis in murine cells, but it reduced TNF-\u03b1-induced necroptosis in MCMV-infected human HT-29 cells. MC159 also differed from M45 in its effect on NF-\u03baB. While MCMV-encoded M45 blocked NF-\u03baB activation by TNF-\u03b1 and interleukin-1\u03b2 (IL-1\u03b2), MC159 inhibited TNF-\u03b1- but not IL-1\u03b2-induced NF-\u03baB activation in infected mouse fibroblasts. These results indicate that the spectrum of MC159's functions differs depending on cell type and expression system and that a cell culture system for the propagation of MCV is needed to determine the biological relevance of presumed viral gene functions.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            MCV is a human-pathogenic poxvirus that cannot be propagated in cell culture or laboratory animals. Therefore, MCV gene products have been studied predominantly in cells expressing individual viral genes. In this study, we analyzed the function of the MCV gene\n            <jats:italic>MC159<\/jats:italic>\n            by expressing it from a different virus and comparing its functions to those of two well-characterized MCMV genes. In this system,\n            <jats:italic>MC159<\/jats:italic>\n            displayed some but not all of the previously described functions, suggesting that the functions of a viral gene depend on the conditions under which it is expressed. Until a cell culture system for the analysis of MCV becomes available, it might be necessary to analyze MCV genes in several different systems to extrapolate their biological importance.\n          <\/jats:p>","DOI":"10.1128\/jvi.02729-15","type":"journal-article","created":{"date-parts":[[2015,12,31]],"date-time":"2015-12-31T02:54:03Z","timestamp":1451530443000},"page":"2895-2905","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":14,"title":["Functional Comparison of Molluscum Contagiosum Virus vFLIP MC159 with Murine Cytomegalovirus M36\/vICA and M45\/vIRA Proteins"],"prefix":"10.1128","volume":"90","author":[{"given":"Julia","family":"H\u00fcttmann","sequence":"first","affiliation":[{"name":"Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, 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