title: BAFF receptor deficiency limits gammaherpesvirus infection.
abstract: Lymphocyte colonization by gammaherpesviruses (γHVs) is an important target for cancer prevention. However, how it works is not clear. Epstein-Barr virus drives autonomous B cell proliferation in vitro but in vivo 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 γHV colonizes B cells in vivo. Not all γHVs 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(+) 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(-/-) 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 in vivo, γHVs mostly induce infected B cells into normal GC reactions rather than generating large numbers of autonomously proliferating blasts.
  
  
  OBJECTIVE
  γHVs 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 γHV requires BAFF-R. This supports the idea that γHVs exploit host proliferation pathways and suggests that interfering with BAFF-R could more generally reduce γHV-associated B cell proliferation.
authors: Division of Virology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors: Bruno
authors: B
authors: Frederico
authors: Janet S
authors: JS
authors: May
authors: Stacey
authors: S
authors: Efstathiou
authors: Philip G
authors: PG
authors: Stevenson
mesh_terms: D000818:Animals; D053264:B-Cell Activating Factor / Q000378:metabolism*; D053265:B-Cell Activation Factor Receptor / Q000172:deficiency* / Q000235:genetics; D001402:B-Lymphocytes / Q000378:metabolism / Q000821:virology; D005260:Female; D018142:Gammaherpesvirinae / Q000235:genetics / Q000502:physiology; D006566:Herpesviridae Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018144:Rhadinovirus / Q000235:genetics / Q000502:physiology*
chemical_list: D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor