Pathogenesis of filoviral haemorrhagic fevers Siddhartha Mahanty, Dr Mike Bray  The Lancet Infectious Diseases  Volume 4, Issue 8, Pages 487-498 (August 2004) DOI: 10.1016/S1473-3099(04)01103-X Copyright © 2004 Elsevier Ltd Terms and Conditions

Figure 1 Zaire ebolavirus. (A) Transmission electron micrograph of virions. (B) Transmission electron micrograph of viral nucleocapsids in a cytoplasmic inclusion body within an infected hepatocyte. (C) Scanning electron micrograph of virions budding from the surface of an infected primary human umbilical-vein endothelial cell. (D) Arrangement of the seven filovirus genes along the single-stranded negative-sense RNA genome; IR=intergenic regions; GP=glycoprotein; NP=nucleoprotein; VP=viral protein; L=large protein (RNA-dependent RNA polymerase). (E) Structure of a filovirus virion. A-C reproduced with permission from T Geisbert (US Army Medical Research Institute of Infectious Diseases). The Lancet Infectious Diseases 2004 4, 487-498DOI: (10.1016/S1473-3099(04)01103-X) Copyright © 2004 Elsevier Ltd Terms and Conditions

Figure 2 Filovirus replication. The steps in replication are described in the text. The Lancet Infectious Diseases 2004 4, 487-498DOI: (10.1016/S1473-3099(04)01103-X) Copyright © 2004 Elsevier Ltd Terms and Conditions

Figure 3 A model of the pathogenesis of filoviral haemorrhagic fever, based on studies of Zaire ebolavirus infection. Infection causes lysis of monocytes/macrophages, dendritic cells, and hepatocytes and suppresses innate immune responses in these cells, aiding further dissemination. Direct injury to infected cells is accompanied by indirect effects that are mediated by proinflammatory and anti-inflammatory effector molecules, including interleukin 1β (IL1β), interleukin 6 (IL6), TNFα, interleukin 10 (IL10), and type I interferons (IFN). The severe illness results from the combined effects of widespread viral cytolysis and massive release of proinflammatory mediators. Proinflammatory cytokines and chemokines are also produced by activated endothelial cells, resulting in a feedback loop to the monocytes/macrophages. Lymphocyte apoptosis is also apparently brought about through effects of proinflammatory mediators; it may contribute to immunosuppression by weakening adaptive immune responses. The cell-surface expression of tissue factor by virus-infected monocytes/macrophages induces disseminated intravascular coagulation (DIC). MCP=monocyte chemoattractant protein; IL1RA=interleukin-1 receptor antagonist. The Lancet Infectious Diseases 2004 4, 487-498DOI: (10.1016/S1473-3099(04)01103-X) Copyright © 2004 Elsevier Ltd Terms and Conditions