{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:19:14Z","timestamp":1791418754505,"version":"4.3.3"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"19","license":[{"start":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T00:00:00Z","timestamp":1475280000000},"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":["J Virol"],"published-print":{"date-parts":[[2016,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            ADP-ribosylation is a posttranslational protein modification in which ADP-ribose is transferred from NAD\n            <jats:sup>+<\/jats:sup>\n            to specific acceptors to regulate a wide variety of cellular processes. The macro domain is an ancient and highly evolutionarily conserved protein domain widely distributed throughout all kingdoms of life, including viruses. The human TARG1\/C6orf130, MacroD1, and MacroD2 proteins can reverse ADP-ribosylation by acting on ADP-ribosylated substrates through the hydrolytic activity of their macro domains. Here, we report that the macro domain from hepatitis E virus (HEV) serves as an ADP-ribose-protein hydrolase for mono-ADP-ribose (MAR) and poly(ADP-ribose) (PAR) chain removal (de-MARylation and de-PARylation, respectively) from mono- and poly(ADP)-ribosylated proteins, respectively. The presence of the HEV helicase in\n            <jats:italic>cis<\/jats:italic>\n            dramatically increases the binding of the macro domain to poly(ADP-ribose) and stimulates the de-PARylation activity. Abrogation of the latter dramatically decreases replication of an HEV subgenomic replicon. The de-MARylation activity is present in all three pathogenic positive-sense, single-stranded RNA [(+)ssRNA] virus families which carry a macro domain:\n            <jats:named-content content-type=\"genus-species\">Coronaviridae<\/jats:named-content>\n            (severe acute respiratory syndrome coronavirus and human coronavirus 229E),\n            <jats:named-content content-type=\"genus-species\">Togaviridae<\/jats:named-content>\n            (Venezuelan equine encephalitis virus), and\n            <jats:named-content content-type=\"genus-species\">Hepeviridae<\/jats:named-content>\n            (HEV), indicating that it might be a significant tropism and\/or pathogenic determinant.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Protein ADP-ribosylation is a covalent posttranslational modification regulating cellular protein activities in a dynamic fashion to modulate and coordinate a variety of cellular processes. Three viral families,\n            <jats:named-content content-type=\"genus-species\">Coronaviridae<\/jats:named-content>\n            ,\n            <jats:named-content content-type=\"genus-species\">Togaviridae<\/jats:named-content>\n            , and\n            <jats:named-content content-type=\"genus-species\">Hepeviridae<\/jats:named-content>\n            , possess macro domains embedded in their polyproteins. Here, we show that viral macro domains reverse cellular ADP-ribosylation, potentially cutting the signal of a viral infection in the cell. Various poly(ADP-ribose) polymerases which are notorious guardians of cellular integrity are demodified by macro domains from members of these virus families. In the case of hepatitis E virus, the adjacent viral helicase domain dramatically increases the binding of the macro domain to PAR and simulates the demodification activity.\n          <\/jats:p>","DOI":"10.1128\/jvi.00705-16","type":"journal-article","created":{"date-parts":[[2016,7,21]],"date-time":"2016-07-21T02:58:58Z","timestamp":1469069938000},"page":"8478-8486","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":181,"title":["Viral Macro Domains Reverse Protein ADP-Ribosylation"],"prefix":"10.1128","volume":"90","author":[{"given":"Changqing","family":"Li","sequence":"first","affiliation":[{"name":"CNRS, AFMB UMR 7257, Marseille, France"},{"name":"Aix-Marseille Universit\u00e9, AFMB UMR 7257, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yannick","family":"Debing","sequence":"additional","affiliation":[{"name":"Rega Institute for Medical Research, Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gytis","family":"Jankevicius","sequence":"additional","affiliation":[{"name":"Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Neyts","sequence":"additional","affiliation":[{"name":"Rega Institute for Medical Research, Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Ahel","sequence":"additional","affiliation":[{"name":"Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Coutard","sequence":"additional","affiliation":[{"name":"CNRS, AFMB UMR 7257, Marseille, France"},{"name":"Aix-Marseille Universit\u00e9, AFMB UMR 7257, Marseille, 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