In Mice, Genetics Dictates Ebola Infection Outcomes

The Outcome of Ebola Infections Often Depends on a Patient's Access to Sophisticated Medical Care. But, there's the Possibility that it Could be Influenced by Genetics as well. That Suggestion Comes from the Authors of a New Paper that Looked at What Happens When Genetically Diverse Groups of Mice were Exposed to the Virus. As it Turns Out, the Results Ranged from Losing a Bit of Weight to Complete Mortality. The Work Doesn't Seem to Have been Inspired by Looking for Insight into the Progression of Hemorrhagic Fever in Humans. Instead, the Researchers Involved, Appear to Have been Frustrated by the Fact that, the Most Convenient Research Mammal, the Mouse, Doesn't Experience the Symptoms Typical of Ebola Infections in Humans: No Problems with Blood Coagulation, No Hemorrhages and No Shock. So, they Decided to See if they Could Find a Mouse Strain that did Show these Symptoms (and Would thus Enable Convenient Studies).


To do so, they Started with Something Called the Collaborative Cross Collection. Most of the Mouse Strains Used in Research Have been Inbred until All Members of the Strain are Genetically Identical. There are, however, Differences between Strains; C57 Mice are Genetically Distinct from 129 Mice. So, it's Possible to See Very Different Things Happen if you do the Same Experiment in Different Strains. The Collaborative Cross Collection Takes this a Step further. In Addition to Having 5 of the Traditional Lab Strains, it has 3 Strains Recently Isolated from Wild Populations and then it Breeds Every Pairwise Combination of the 8 Strains. The Result is a Very Large Collection of Mice that are Genetic Hybrids. Infecting the Hybrids Produced All Sorts of Results. In Some Strains, the Virus had No Effect Whatsoever. In Others, it Killed without Causing any Obvious Symptoms. Still Others Showed a Human-Like Progression through Hemorrhagic Fever to Death. Focusing on 2 Specific Strains, the Authors Found that, Both Lost about 15% of their Body Weight within the 1st 5 Days of Infection.


But on Day 6, One Strain Started to Die, while the Other Recovered. There were Similar Levels of Viral RNA in Both Strains; the Susceptible One just Made Far More Viruses Using that RNA. The Authors were Able to See Differences in Gene Activity Following Infection in the 2 Strains, including Some Indicating that, the Resistant Strain Begins to Activate Genes Needed to Repair Blood Vessels as the Infection Proceeds. In Addition to Indicating that, we Can Now Study Hemorrhagic Fever in Mice, the Results May Tell us Something about the Trajectory of Outbreaks in Humans. Follow-Up Studies Have Shown that, Even in the Same Outbreak, Ebola Infection, Causes Different Responses in Humans. As the Authors Note, "This suggests that the host response may determine disease severity after EBOV infection". In Situations like this, there is Always a Range of Factors that Can Contribute — Health Status Prior to Infection, Quality of Care, Speed of Diagnosis, Genetic Changes in the Virus and so on. But, the New Work Suggests that, Genetic Contributions of the Host, May Influence Disease Progression as well.