Fibroblastic reticular cell infection by hemorrhagic fever viruses.
Viral hemorrhagic fevers (VHFs) often cause high mortality with high infectivity, multiorgan failure, shock and hemorrhagic diathesis. Fibroblastic reticular cells (FRCs) within secondary lymphoid organs provide a supporting scaffold to T-lymphocyte areas. These cells regulate the movement of various immune cells and soluble molecules that promote T-lymphocyte homeostasis. We previously reported Ebola virus infection of FRCs, but ascribed little significance to this finding. Here, we studied infection of FRCs by Ebola, Marburg and Lassa viruses. We demonstrate that FRCs, or the extracellular 'conduit' of the fibroblastic reticulum of nonhuman primates, are targets of Ebola, Marburg and Lassa viruses. Furthermore, we observed that FRC damage correlates temporally and spatially with lymphocyte damage and that FRCs serve as nidi of fibrin deposition. In addition, we show that nonhuman primate FRCs express p75 NGF receptor and tissue transglutaminase. Our data suggest that viral infection of FRCs may be crucial to the immunological dysfunction and coagulopathy characteristic of VHFs. We further propose that p75 NGF receptor and tissue transglutaminase may be involved in FRC-associated dysfunction during the course of infection.
Steele
Keith E
KE
Division of Pathology, US Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Frederick, MD 21702, USA. keith.steele1@us.army.mil
Anderson
Arthur O
AO
Mohamadzadeh
Mansour
M
D000818:Animals; D001778:Blood Coagulation Disorders; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005347:Fibroblasts / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D006482:Hemorrhagic Fevers, Viral / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology*; D018613:Microscopy, Confocal; D010446:Peptide Fragments / Q000378:metabolism; D011323:Primates; D012328:RNA Viruses / Q000276:immunology* / Q000472:pathogenicity; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000821:virology
D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; D020800:Receptor, Nerve Growth Factor; C033786:fibrinogen Bbeta (15-42)