title: Retroviruses use CD169-mediated trans-infection of permissive lymphocytes to establish infection.
abstract: Dendritic cells can capture and transfer retroviruses in vitro across synaptic cell-cell contacts to uninfected cells, a process called trans-infection. Whether trans-infection contributes to retroviral spread in vivo remains unknown. Here, we visualize how retroviruses disseminate in secondary lymphoid tissues of living mice. We demonstrate that murine leukemia virus (MLV) and human immunodeficiency virus (HIV) are first captured by sinus-lining macrophages. CD169/Siglec-1, an I-type lectin that recognizes gangliosides, captures the virus. MLV-laden macrophages then form long-lived synaptic contacts to trans-infect B-1 cells. Infected B-1 cells subsequently migrate into the lymph node to spread the infection through virological synapses. Robust infection in lymph nodes and spleen requires CD169, suggesting that a combination of fluid-based movement followed by CD169-dependent trans-infection can contribute to viral spread.
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Xaver
authors.initials: X
authors.lastname: Sewald
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Ladinsky
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Pradeep D
authors.initials: PD
authors.lastname: Uchil
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Jagadish
authors.initials: J
authors.lastname: Beloor
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Ruoxi
authors.initials: R
authors.lastname: Pi
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Christin
authors.initials: C
authors.lastname: Herrmann
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Nasim
authors.initials: N
authors.lastname: Motamedi
authors.affiliation: Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Thomas T
authors.initials: TT
authors.lastname: Murooka
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Brehm
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01655, USA.
authors.forename: Dale L
authors.initials: DL
authors.lastname: Greiner
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME 04609, USA..
authors.forename: Leonard D
authors.initials: LD
authors.lastname: Shultz
authors.affiliation: Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Thorsten R
authors.initials: TR
authors.lastname: Mempel
authors.affiliation: Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Bjorkman
authors.affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Priti
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Walther
authors.initials: W
authors.lastname: Mothes
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D009052:Leukemia Virus, Murine / Q000502:physiology*; D008198:Lymph Nodes / Q000276:immunology / Q000821:virology; D008214:Lymphocytes / Q000276:immunology / Q000821:virology*; D008264:Macrophages / Q000276:immunology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012192:Retroviridae Infections / Q000276:immunology*; D063267:Sialic Acid Binding Ig-like Lectin 1 / Q000235:genetics / Q000502:physiology*; D013154:Spleen / Q000276:immunology / Q000821:virology; D053586:Virus Internalization
chemical_list: D063267:Sialic Acid Binding Ig-like Lectin 1; C571167:Siglec1 protein, mouse