title: Subcapsular sinus macrophages limit acute gammaherpesvirus dissemination.
abstract: Lymphocyte proliferation, mobility and longevity make them prime targets for virus infection. Myeloid cells that process and present environmental antigens to lymphocytes are consequently an important line of defence. Subcapsular sinus macrophages (SSMs) filter the afferent lymph and communicate with B-cells. How they interact with B-cell-tropic viruses is unknown. We analysed their encounter with murid herpesvirus-4 (MuHV-4), an experimentally accessible gammaherpesvirus related to Kaposi's sarcoma-associated herpesvirus. MuHV-4 disseminated via lymph nodes, and intranasally or subcutaneously inoculated virions readily infected SSMs. However, this infection was poorly productive. SSM depletion with clodronate-loaded liposomes or with diphtheria toxin in CD169-diphtheria toxin receptor transgenic mice increased B-cell infection and hastened virus spread to the spleen. Dendritic cells provided the main route to B-cells, and SSMs slowed host colonization, apparently by absorbing virions non-productively from the afferent lymph.
authors: Division of Virology, Department of Pathology, University of Cambridge, Cambridge, UK.
authors: Bruno
authors: B
authors: Frederico
authors: Division of Virology, Department of Pathology, University of Cambridge, Cambridge, UK.
authors: Brittany
authors: B
authors: Chao
authors: Sir Albert Sakzewski Virus Research Centre, Clinical Medical Virology Centre, School of Chemistry and Molecular Biosciences, Royal Children's Hospital and University of Queensland, Brisbane, Australia.
authors: Clara
authors: C
authors: Lawler
authors: Division of Virology, Department of Pathology, University of Cambridge, Cambridge, UK.
authors: Janet S
authors: JS
authors: May
authors: Division of Virology, Department of Pathology, University of Cambridge, Cambridge, UK.|Sir Albert Sakzewski Virus Research Centre, Clinical Medical Virology Centre, School of Chemistry and Molecular Biosciences, Royal Children's Hospital and University of Queensland, Brisbane, Australia.
authors: Philip G
authors: PG
authors: Stevenson
mesh_terms: D000818:Animals; D006566:Herpesviridae Infections / Q000276:immunology / Q000821:virology*; D006801:Humans; D008198:Lymph Nodes / Q000821:virology; D008264:Macrophages / Q000276:immunology / Q000821:virology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018144:Rhadinovirus / Q000235:genetics / Q000276:immunology / Q000502:physiology*