{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T14:50:14Z","timestamp":1769266214465,"version":"3.49.0"},"reference-count":31,"publisher":"American Society for Microbiology","issue":"13","license":[{"start":{"date-parts":[[2018,6,13]],"date-time":"2018-06-13T00:00:00Z","timestamp":1528848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2018,7,1]],"date-time":"2018-07-01T00:00:00Z","timestamp":1530403200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100005825","name":"USDA | National Institute of Food and Agriculture","doi-asserted-by":"publisher","award":["2009-35204-05200"],"award-info":[{"award-number":["2009-35204-05200"]}],"id":[{"id":"10.13039\/100005825","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005825","name":"USDA | National Institute of Food and Agriculture","doi-asserted-by":"publisher","award":["2015-67015-23277"],"award-info":[{"award-number":["2015-67015-23277"]}],"id":[{"id":"10.13039\/100005825","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2018,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Alphaherpesvirus envelope glycoprotein N (gN) and gM form a covalently linked complex. Bovine herpesvirus type 1 (BHV-1) U\n            <jats:sub>L<\/jats:sub>\n            49.5 (a gN homolog) contains two predicted cysteine residues, C42 and C78. The C42 is highly conserved among the alphaherpesvirus gN homologs (e.g., herpes simplex virus 1 and pseudorabies virus). To identify which cysteine residue is required for the formation of the U\n            <jats:sub>L<\/jats:sub>\n            49.5\/gM complex and to characterize the functional significance of the U\n            <jats:sub>L<\/jats:sub>\n            49.5\/gM complex, we constructed and analyzed C42S and C78S substitution mutants in either a BHV-1 wild type (wt) or BHV-1 U\n            <jats:sub>L<\/jats:sub>\n            49.5 cytoplasmic tail-null (CT-null) virus background. The results demonstrated that BHV-1 U\n            <jats:sub>L<\/jats:sub>\n            49.5 residue C42 but not C78 was essential for the formation of the covalently linked functional U\n            <jats:sub>L<\/jats:sub>\n            49.5\/gM complex, gM maturation in the Golgi compartment, and efficient cell-to-cell spread of the virus. Interestingly, the C42S and CT-null mutations separately did not affect mutant U\n            <jats:sub>L<\/jats:sub>\n            49.5 virion incorporation. However, when both of the mutations were introduced simultaneously, the U\n            <jats:sub>L<\/jats:sub>\n            49.5 C42S\/CT-null protein virion incorporation was severely reduced. Incidentally, the anti-VP22 antibody coimmunoprecipitated the U\n            <jats:sub>L<\/jats:sub>\n            49.5 C42S\/CT-null mutant protein at a noticeably reduced level compared to that of the individual U\n            <jats:sub>L<\/jats:sub>\n            49.5 C42S and CT-null mutant proteins. As expected, in a dual U\n            <jats:sub>L<\/jats:sub>\n            49.5 C42S\/VP22\u0394 virus with deletion of VP22 (VP22\u0394), the U\n            <jats:sub>L<\/jats:sub>\n            49.5 C42S virion incorporation was also severely reduced while in a gM\u0394 virus, U\n            <jats:sub>L<\/jats:sub>\n            49.5 virion incorporation was affected only slightly. Together, these results suggested that U\n            <jats:sub>L<\/jats:sub>\n            49.5 virion incorporation is mediated redundantly, by both U\n            <jats:sub>L<\/jats:sub>\n            49.5\/gM functional complex and VP22, through a putative gM-independent novel U\n            <jats:sub>L<\/jats:sub>\n            49.5 and VP22 interaction.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Bovine herpesvirus 1 (BHV-1) envelope protein U\n            <jats:sub>L<\/jats:sub>\n            49.5 is an important virulence determinant because it downregulates major histocompatibility complex class I (MHC-I). U\n            <jats:sub>L<\/jats:sub>\n            49.5 also forms a covalently linked complex with gM. The results of this study demonstrate that U\n            <jats:sub>L<\/jats:sub>\n            49.5 regulates gM maturation and virus cell-to-cell spread since gM maturation in the Golgi compartment depends on covalently linked U\n            <jats:sub>L<\/jats:sub>\n            49.5\/gM complex. The results also show that the U\n            <jats:sub>L<\/jats:sub>\n            49.5 residue cysteine 42 (C42) mediates the formation of the covalently linked U\n            <jats:sub>L<\/jats:sub>\n            49.5-gM interaction. Furthermore, a C42S mutant virus in which U\n            <jats:sub>L<\/jats:sub>\n            49.5 cannot interact with gM has defective cell-to-cell spread. Interestingly, U\n            <jats:sub>L<\/jats:sub>\n            49.5 also interacts with the tegument protein VP22 via its cytoplasmic tail (CT). The putative U\n            <jats:sub>L<\/jats:sub>\n            49.5 CT-VP22 interaction is essential for a gM-independent U\n            <jats:sub>L<\/jats:sub>\n            49.5 virion incorporation and is revealed when U\n            <jats:sub>L<\/jats:sub>\n            49.5 and gM are not linked. Therefore, U\n            <jats:sub>L<\/jats:sub>\n            49.5 virion incorporation is mediated by U\n            <jats:sub>L<\/jats:sub>\n            49.5-gM complex interaction and through a gM-independent interaction between U\n            <jats:sub>L<\/jats:sub>\n            49.5 and VP22.\n          <\/jats:p>","DOI":"10.1128\/jvi.00240-18","type":"journal-article","created":{"date-parts":[[2018,4,13]],"date-time":"2018-04-13T10:38:26Z","timestamp":1523615906000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":15,"title":["Bovine Herpesvirus 1 U\n            <sub>L<\/sub>\n            49.5 Interacts with gM and VP22 To Ensure Virus Cell-to-Cell Spread and Virion Incorporation: Novel Role for VP22 in gM-Independent U\n            <sub>L<\/sub>\n            49.5 Virion Incorporation"],"prefix":"10.1128","volume":"92","author":[{"given":"Katrin","family":"Pannhorst","sequence":"first","affiliation":[{"name":"Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huiyong","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hocine","family":"Yezid","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junyun","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences, School of Veterinary 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