A recent study shows that a mouse model of Ebola produces a variety of different symptoms in each model mimicking the variations in degree of Ebola’s symptoms in humans. Nineteen percent of the mouse models remained unaffected by the disease while many mice died from it. The different outcomes of symptoms in mice and humans are likely contributed to differences in genes between the mice. In particular different genes for blood coagulation and clotting affected the severity of Ebola’s symptoms.
Until recently a mouse model did not exist for Ebola, and thus the researchers used a mouse-adaptaed (MA-EBOV) strain of the virus. The mouse model is easier and less ethically controversial model than non-human primates for studying the disease. Hopefully the use of a new animal model will accelerate advances in research about the Ebola Virus. However, MA-EBOV does not progress to Ebola Hemorrhagic Fever (EHF) but still causes lethal disease with other similar symptoms to humans. EHF is actually not apparent in most humans, but the disease is still lethal as people’s immune response overreacts to the virus, causing an inflammatory response that deteriorates internal organs.
This deterioration of organs is due to the increased vascularization of epithelial cells. Ebola and similar viruses interfere with the coagulation pathway notoriously causing vascular leakage and difficulty clotting. Some mice are able to better counteract the virus by increasing expression of the TIE1 and TEK pathway, which activate blood clotting chemicals such as thrombin and tissue factor. Analysis revealed that certain Tek and Tie1 alleles had a greater propensity to ward off symptoms or sickness altogether.
EHF exists in 30-50% of the human population with Ebola. Immunity to other viruses has been theorized as the primary reason some people get less severe symptoms. But this study reveals a significant advance in the understanding of the genetic contribution to Ebola survival. However, the study ignores any environmental component that may influence disease factors, but nonetheless represents a great step forward and a promising launching point for further research.
--Will St. Amant