title: Tissue tropism and target cells of NSs-deleted rift valley fever virus in live immunodeficient mice.
abstract: BACKGROUND
  Rift Valley fever virus (RVFV) causes disease in livestock and humans. It can be transmitted by mosquitoes, inhalation or physical contact with the body fluids of infected animals. Severe clinical cases are characterized by acute hepatitis with hemorrhage, meningoencephalitis and/or retinitis. The dynamics of RVFV infection and the cell types infected in vivo are poorly understood.
  
  
  RESULTS
  RVFV strains expressing humanized Renilla luciferase (hRLuc) or green fluorescent protein (GFP) were generated and inoculated to susceptible Ifnar1-deficient mice. We investigated the tissue tropism in these mice and the nature of the target cells in vivo using whole-organ imaging and flow cytometry. After intraperitoneal inoculation, hRLuc signal was observed primarily in the thymus, spleen and liver. Macrophages infiltrating various tissues, in particular the adipose tissue surrounding the pancreas also expressed the virus. The liver rapidly turned into the major luminescent organ and the mice succumbed to severe hepatitis. The brain remained weakly luminescent throughout infection. FACS analysis in RVFV-GFP-infected mice showed that the macrophages, dendritic cells and granulocytes were main target cells for RVFV. The crucial role of cells of the monocyte/macrophage/dendritic lineage during RVFV infection was confirmed by the slower viral dissemination, decrease in RVFV titers in blood, and prolonged survival of macrophage- and dendritic cell-depleted mice following treatment with clodronate liposomes. Upon dermal and nasal inoculations, the viral dissemination was primarily observed in the lymph node draining the injected ear and in the lungs respectively, with a significant increase in survival time.
  
  
  CONCLUSIONS
  These findings reveal the high levels of phagocytic cells harboring RVFV during viral infection in Ifnar1-deficient mice. They demonstrate that bioluminescent and fluorescent viruses can shed new light into the pathogenesis of RVFV infection.
authors.affiliation: Central Animal Facilities, Institut Pasteur, Paris, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Gommet
authors.forename: Agnès
authors.initials: A
authors.lastname: Billecocq
authors.forename: Grégory
authors.initials: G
authors.lastname: Jouvion
authors.forename: Milena
authors.initials: M
authors.lastname: Hasan
authors.forename: Tânia
authors.initials: T
authors.lastname: Zaverucha do Valle
authors.forename: Laurent
authors.initials: L
authors.lastname: Guillemot
authors.forename: Charlène
authors.initials: C
authors.lastname: Blanchet
authors.forename: Nico
authors.initials: N
authors.lastname: van Rooijen
authors.forename: Xavier
authors.initials: X
authors.lastname: Montagutelli
authors.forename: Michèle
authors.initials: M
authors.lastname: Bouloy
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Panthier
mesh_terms: D000818:Animals; D004002:Clodronic Acid; D005434:Flow Cytometry; D055786:Gene Knockout Techniques; D049452:Green Fluorescent Proteins / Q000235:genetics; D007150:Immunohistochemistry; D008081:Liposomes; D008099:Liver / Q000821:virology*; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D010179:Pancreas / Q000821:virology; D010586:Phagocytes / Q000821:virology*; D012295:Rift Valley Fever / Q000503:physiopathology / Q000821:virology*; D012296:Rift Valley fever virus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D016019:Survival Analysis; D013950:Thymus Gland / Q000821:virology; D014709:Vero Cells; D017361:Viral Nonstructural Proteins / Q000235:genetics
chemical_list: D008081:Liposomes; D017361:Viral Nonstructural Proteins; D004002:Clodronic Acid; D049452:Green Fluorescent Proteins