{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T06:16:37Z","timestamp":1773296197241,"version":"3.50.1"},"reference-count":54,"publisher":"Microbiology Society","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,12,1]]},"abstract":"<jats:p>\n                  <jats:italic>In vitro<\/jats:italic> studies have established that the latency-associated nuclear antigen encoded by human Kaposi's sarcoma-associated herpesvirus and the related ORF73 gene product of herpesvirus saimiri interact with virus origins of replication to facilitate maintenance of episomal DNA. Such a function implies a critical role for ORF73 in the establishment and maintenance of latency <jats:italic>in vivo<\/jats:italic>. To determine the role of ORF73 in virus pathogenesis, the ORF73 gene product encoded by murine herpesvirus-68 (MHV-68) was disrupted by making an ORF73 deletion mutant, \u039473, and an independent ORF73 frameshift mutant, FS73. The effect of the mutations introduced in ORF73 on MHV-68 pathogenesis was analysed <jats:italic>in vivo<\/jats:italic> using a well-characterized murine model system. These studies have revealed that ORF73 is not required for efficient lytic replication either <jats:italic>in vitro<\/jats:italic> or <jats:italic>in vivo<\/jats:italic>. In contrast, a severe latency deficit is observed in splenocytes of animals infected with an ORF73 mutant, as assessed by infectious centre reactivation assay or by <jats:italic>in situ<\/jats:italic> hybridization detection of latent virus. Assessment of viral genome-positive cells in sorted splenocyte populations confirmed the absence of ORF73 mutant virus from splenic latency reservoirs, including germinal centre B cells. These data indicate a crucial role for ORF73 in the establishment of latency and for virus persistence in the host.<\/jats:p>","DOI":"10.1099\/vir.0.19594-0","type":"journal-article","created":{"date-parts":[[2003,11,26]],"date-time":"2003-11-26T23:59:02Z","timestamp":1069891142000},"page":"3405-3416","source":"Crossref","is-referenced-by-count":87,"title":["ORF73 of murine herpesvirus-68 is critical for the establishment and maintenance of latency"],"prefix":"10.1099","volume":"84","author":[{"given":"Polly","family":"Fowler","sequence":"first","affiliation":[{"name":"Division of Virology, Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK"}]},{"given":"Sofia","family":"Marques","sequence":"additional","affiliation":[{"name":"Laboratory of Microbiology, Faculty of Medicine, University of Lisbon, 1649-028 Lisbon, Portugal"},{"name":"Instituto Gulbenkian de Cie\u02c6ncia, 2780-156 Oeiras, Portugal"}]},{"given":"J. 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