{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T21:40:10Z","timestamp":1762033210813},"reference-count":67,"publisher":"American Society for Microbiology","issue":"16","license":[{"start":{"date-parts":[[2014,8,15]],"date-time":"2014-08-15T00:00:00Z","timestamp":1408060800000},"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":[[2014,8,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The UL128 complex of human cytomegalovirus (CMV) is a major determinant of viral entry into epithelial and endothelial cells and a target for vaccine development. The UL\/b\u2032 region of rhesus CMV contains several open reading frames, including orthologs of the UL128 complex. We recently showed that the coding content of the rhesus CMV (RhCMV) UL\/b\u2032 region predicts acute endothelial tropism and long-term shedding<jats:italic>in vivo<\/jats:italic>in the rhesus macaque model of CMV infection. The laboratory-passaged RhCMV 180.92 strain has a truncated UL\/b\u2032 region but an intact UL128 complex. To investigate whether the presence of the UL128 complex alone was sufficient to confer endothelial and epithelial tropism<jats:italic>in vivo<\/jats:italic>, we investigated tissue dissemination and viral excretion following experimental RhCMV 180.92 inoculation of RhCMV-seronegative rhesus macaques. We show the presence of at least two virus variants in the RhCMV 180.92 infectious virus stock. A rare variant noted for a nontruncated wild-type-virus-like UL\/b\u2032 region, rapidly emerged during<jats:italic>in vivo<\/jats:italic>replication and showed high-level replication in blood and tissues and excretion in urine and saliva, features similar to those previously reported in naturally occurring wild-type RhCMV infection. In contrast, the predominant truncated version of RhCMV 180.92 showed significantly lower plasma DNAemia and limited tissue dissemination and viral shedding. These data demonstrate that the truncated RhCMV 180.92 variant is attenuated<jats:italic>in vivo<\/jats:italic>and suggest that additional UL\/b\u2032 genes, besides the UL128 complex, are required for optimal<jats:italic>in vivo<\/jats:italic>CMV replication and dissemination.<\/jats:p><jats:p><jats:bold>IMPORTANCE<\/jats:bold>An effective vaccine against human CMV infection will need to target genes that are essential for virus propagation and transmission. The human CMV UL128 complex represents one such candidate antigen since it is essential for endothelial and epithelial cell tropism, and is a target for neutralizing antibodies in CMV-infected individuals. In this study, we used the rhesus macaque animal model of CMV infection to investigate the<jats:italic>in vivo<\/jats:italic>function of the UL128 complex. Using experimental infection of rhesus macaques with a rhesus CMV virus variant that contained an intact UL128 complex but was missing several other genes, we show that the presence of the UL128 complex alone is not sufficient for widespread tissue dissemination and virus excretion. These data highlight the importance of<jats:italic>in vivo<\/jats:italic>studies in evaluating human CMV gene function and suggest that additional UL\/b\u2032 genes are required for optimal CMV dissemination and transmission.<\/jats:p>","DOI":"10.1128\/jvi.00162-14","type":"journal-article","created":{"date-parts":[[2014,6,5]],"date-time":"2014-06-05T01:56:57Z","timestamp":1401933417000},"page":"9310-9320","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":21,"title":["Limited Dissemination and Shedding of the UL128 Complex-Intact, UL\/b\u2032-Defective Rhesus Cytomegalovirus Strain 180.92"],"prefix":"10.1128","volume":"88","author":[{"given":"Basel T.","family":"Assaf","sequence":"first","affiliation":[{"name":"Division of Comparative Pathology, New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts, USA"},{"name":"Center for Comparative Medicine, University of California, Davis, Davis, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith G.","family":"Mansfield","sequence":"additional","affiliation":[{"name":"Division of Comparative Pathology, New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Strelow","sequence":"additional","affiliation":[{"name":"Center for Comparative Medicine, University of California, Davis, Davis, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan V.","family":"Westmoreland","sequence":"additional","affiliation":[{"name":"Division of Comparative Pathology, New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter A.","family":"Barry","sequence":"additional","affiliation":[{"name":"Center for Comparative Medicine, University of California, Davis, Davis, California, USA"},{"name":"Department of Pathology and Laboratory Medicine, University of California, Davis, Davis, California, USA"},{"name":"California National Primate Research Center, University of California, Davis, Davis, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amitinder","family":"Kaur","sequence":"additional","affiliation":[{"name":"Division of Immunology, New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/rmv.655"},{"key":"e_1_3_2_3_2","volume-title":"Fields virology","author":"Fields BN","year":"2007","unstructured":"FieldsBNKnipeDMHowleyPM. 2007. 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