{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T02:19:01Z","timestamp":1717726741095},"reference-count":54,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2014,3,26]],"date-time":"2014-03-26T00:00:00Z","timestamp":1395792000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"},{"start":{"date-parts":[[2014,4,15]],"date-time":"2014-04-15T00:00:00Z","timestamp":1397520000000},"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":[[2014,4,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Lymphocyte colonization by gammaherpesviruses (\u03b3HVs) is an important target for cancer prevention. However, how it works is not clear. Epstein-Barr virus drives autonomous B cell proliferation<jats:italic>in vitro<\/jats:italic>but<jats:italic>in vivo<\/jats:italic>may more subtly exploit the proliferative pathways provided by lymphoid germinal centers (GCs). Murid herpesvirus 4 (MuHV-4), which realistically infects inbred mice, provides a useful tool with which to understand further how a \u03b3HV colonizes B cells<jats:italic>in vivo<\/jats:italic>. Not all \u03b3HVs necessarily behave the same, but common events can with MuHV-4 be assigned an importance for host colonization and so a potential as therapeutic targets. MuHV-4-driven B cell proliferation depends quantitatively on CD4<jats:sup>+<\/jats:sup>T cell help. Here we show that it also depends on T cell-independent survival signals provided by the B cell-activating factor (BAFF) receptor (BAFF-R). B cells could be infected in BAFF-R<jats:sup>\u2212\/\u2212<\/jats:sup>mice, but virus loads remained low. This corresponded to a BAFF-R-dependent defect in GC colonization. The close parallels between normal, antigen-driven B cell responses and virus-infected B cell proliferation argue that<jats:italic>in vivo<\/jats:italic>, \u03b3HVs mostly induce infected B cells into normal GC reactions rather than generating large numbers of autonomously proliferating blasts.<\/jats:p><jats:p><jats:bold>IMPORTANCE<\/jats:bold>\u03b3HVs cause cancers by driving the proliferation of infected cells. B cells are a particular target. Thus, we need to know how virus-driven B cell proliferation works. Controversy exists as to whether viral genes drive it directly or less directly orchestrate the engagement of normal, host-driven pathways. Here we show that the B cell proliferation driven by a murid \u03b3HV requires BAFF-R. This supports the idea that \u03b3HVs exploit host proliferation pathways and suggests that interfering with BAFF-R could more generally reduce \u03b3HV-associated B cell proliferation.<\/jats:p>","DOI":"10.1128\/jvi.03497-13","type":"journal-article","created":{"date-parts":[[2014,2,6]],"date-time":"2014-02-06T03:09:48Z","timestamp":1391656188000},"page":"3965-3975","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["BAFF Receptor Deficiency Limits Gammaherpesvirus Infection"],"prefix":"10.1128","volume":"88","author":[{"given":"Bruno","family":"Frederico","sequence":"first","affiliation":[{"name":"Division of Virology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janet S.","family":"May","sequence":"additional","affiliation":[{"name":"Division of Virology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stacey","family":"Efstathiou","sequence":"additional","affiliation":[{"name":"Division of Virology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip G.","family":"Stevenson","sequence":"additional","affiliation":[{"name":"Division of Virology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom"},{"name":"SASVRC\/CMVC, University of Queensland, Royal Children's Hospital, Herston, Brisbane, Queensland, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.81598-0"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.190.4.567"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.10.5194-5204.2004"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0509311102"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002220"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-78-7-1675"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20020890"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.13.7308-7318.2003"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.77.15.8310-8321.2003"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7725108"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0952-7915(94)90141-4"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1099\/vir.0.013300-0"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-072710-081639"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.2.1075-1079.1999"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.4.1820"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-77-4-627"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.73.11.9650-9654.1999"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.2.886"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1061964"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2011.01067.x"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830210506"},{"key":"e_1_3_2_23_2","doi-asserted-by":"crossref","first-page":"598","DOI":"10.4049\/jimmunol.157.2.598","article-title":"Bcmd governs recruitment of new B cells into the stable peripheral B cell pool in the A\/WySnJ mouse","volume":"157","author":"Lentz VM","year":"1996","unstructured":"LentzVMCancroMPNasholdFEHayesCE. 1996. 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