Abstract
Ebola virus (EBOV) is a filamentous negative-strand RNA virus with a glycoprotein envelope and comprises four species, Zaire, Sudan, Ivory Coast and Reston. It is a highly lethal pathogen for humans as well as non-human primates, and has been responsible for numerous African epidemics of viral hemorrhagic fever over the past 29 years. There is also concern that EBOV might be used as an aerosol-transmitted bioterrorism agent. The syndrome of Ebola hemorrhagic fever (EHF) is a paradigm of multiorgan dysfunction characterized by a macular rash, disseminated intravascular coagulopathy (DIC), severe lymphocyte apoptosis, profound hypotension and a failed adaptive immune response to EBOV. Pathogenetic studies in non-human primates have shown that EHF stems from early EBOV infection of dendritic cells and that the DIC is associated with up-regulated tissue factor expression in EBOV-infected monocytes/macrophages and on microparticles released from these cells. Although there is no efficacious antiviral treatment for EHF, encouraging results have been noted in EBOV-infected monkeys treated with the anticoagulant, rNAPc2. There is also no FDA-approved Ebola vaccine for human use, but several candidate vaccines have been tested in both rodents and monkeys using a variety of delivery systems. Highly promising results have been obtained in cynomolgus macaques with one-shot vaccines using either adenovirus or attenuated vesicular stomatitis virus delivery platforms. Both vector-based vaccines were shown to be protective against a robust EBOV challenge.
| Abbreviations | ||
| ADV | = | adenovirus |
| CDC | = | Centers for Disease Control and Prevention |
| DIC | = | disseminated intravascular coagulopathy |
| DRC | = | Democratic Republic of the Congo |
| EBOV | = | Ebola virus |
| EBOV-Z | = | Zaire EBOV |
| EHF | = | Ebola hemorrhagic fever |
| FDA | = | Food and Drug Administration |
| HPMEC | = | human pulmonary microvascular endothelial cells |
| HUVEC | = | human umbilical vein endothelial cells |
| IFN | = | interferon |
| IgG | = | immunoglobulin G |
| IgM | = | immunoglobulin M |
| IL | = | interleukin |
| IRF-3 | = | interferon regulatory factor-3 |
| MBGV | = | Marburg virus |
| MHC | = | major histocompatibility complex |
| MIP-1 | = | macrophage inflammatory protein-1 |
| NK | = | natural killer |
| NP | = | nucleoprotein |
| pfu | = | plaque-forming units |
| SAH | = | S-adenosylhomocysteine hydrolase |
| sFAS | = | soluble FAS |
| TF | = | tissue factor |
| TNF | = | tumor necrosis factor |
| tPA | = | tissue type plasminogen activator antigen |
| TRAIL | = | TNF-related apoptosis-inducing ligand |
| USAMRIID | = | US Army Medical Research Institute for Infectious Diseases |
| VLP | = | virus-like particle |
| VSV | = | vesicular stomatitis virus |
| Abbreviations | ||
| ADV | = | adenovirus |
| CDC | = | Centers for Disease Control and Prevention |
| DIC | = | disseminated intravascular coagulopathy |
| DRC | = | Democratic Republic of the Congo |
| EBOV | = | Ebola virus |
| EBOV-Z | = | Zaire EBOV |
| EHF | = | Ebola hemorrhagic fever |
| FDA | = | Food and Drug Administration |
| HPMEC | = | human pulmonary microvascular endothelial cells |
| HUVEC | = | human umbilical vein endothelial cells |
| IFN | = | interferon |
| IgG | = | immunoglobulin G |
| IgM | = | immunoglobulin M |
| IL | = | interleukin |
| IRF-3 | = | interferon regulatory factor-3 |
| MBGV | = | Marburg virus |
| MHC | = | major histocompatibility complex |
| MIP-1 | = | macrophage inflammatory protein-1 |
| NK | = | natural killer |
| NP | = | nucleoprotein |
| pfu | = | plaque-forming units |
| SAH | = | S-adenosylhomocysteine hydrolase |
| sFAS | = | soluble FAS |
| TF | = | tissue factor |
| TNF | = | tumor necrosis factor |
| tPA | = | tissue type plasminogen activator antigen |
| TRAIL | = | TNF-related apoptosis-inducing ligand |
| USAMRIID | = | US Army Medical Research Institute for Infectious Diseases |
| VLP | = | virus-like particle |
| VSV | = | vesicular stomatitis virus |