It’s only taken 30 years, but information about Ebola in nature is finally starting to snowball. First, after almost 15 years of disappearing from the human population, Ebola returned with a vengeance in the mid 1990s, causing illness in 6 separate outbreaks in Gabon, Ivory Coast, Democratic Republic of Congo (DRC), and South Africa (imported case) between 1994 and 1996. As doctors and scientists rushed in to contain the outbreaks, they were also able to collect viral samples, and trap animals and insects in the area, searching for a reservoir for the virus. In this decade, there have been almost yearly outbreaks of Ebola and/or the closely related Marburg virus in Africa, resulting in the discovery of both Ebola and Marburg infection in species of fruit bats–suggesting these animals may be a reservoir species for filoviruses (though more work remains to be done to confirm this).
As I blogged about previously, prior work has suggested that the most deadly Ebola subtype, known as Ebola-Zaire (EBO-Z) after its initial site of isolation, has been spreading steadily eastward across the central African continent. This was tracked by examining isolates of the virus obtained during human epidemics, which introduces a bias into the sample. However, viral isolates from other sources have been quite difficult to obtain, despite many years of searching. A new paper examines viral isolates collected from dead gorillas and reconstructs their phylogeny in an effort to fill in some of these gaps; more after the jump.
Though human Ebola outbreaks get most of the attention, the virus has actually been far worse on other primates, particularly chimps and gorillas. Unfortunately though, we’ve mostly only seen the carnage in these primate populations after the fact, when workers at wildlife sanctuaries stopped seeing apes they’d become familiar with, or researchers happened upon their corpses in the forest.
The latest paper used some of these tragic deaths to further our understanding about Ebola. Over a 5 year time period, researchers found 47 dead animals in the Gabon/Republic of Congo region–17 of these were determined to be infected with Ebola-Zaire. Using the polymerase chain reaction, they were able to amplify portions of the glycoprotein gene (GP) from 6 gorillas and a chimpanzee, and compare the sequences to those previously identified in humans. When they compared the sequence to other EBO-Z GP sequences published to date, they found that these new genes were divergent enough to constitute a new group within the EBO-Z subtype–and that recent human cases from the Republic of Congo during the same time frame also fit into this new group (designated group B; the previous identified groups were group A, which included sequences from the 1976 outbreak and several outbreaks in the mid-1990s, and group R, from outbreaks between 2001-3).
They also sequenced a second viral gene, encoding the nucleoprotein (NP). For this they were only able to get sequence from 2 gorillas, as well as from human outbreaks during this time period. They found again that the sequences from this gene were closely related to each other, but more divergent from previously deposited sequences. Interestingly, some of the viruses that fit into group A by virtue of their GP sequence weren’t found to be genetically distinct from the group B viruses when looking at the NP sequence, which the authors suggest could be due to a recombination event.
They next track the recent outbreaks across Africa by EBO-Z group (green: oldest lineages, group A; blue, group R; red, group B.)
While upon initial glance this appears to support the previous research regarding Ebola’s eastward spread, the authors argue against this simpler explanation, noting that their new data show that the most recent outbreaks weren’t caused by descendants of previously emerging viruses, but by genetically different types of EBO-Z. Therefore, this draws into question the previous research painting EBO-Z emergence as the radiation of a single viral lineage (acquiring minor mutations along the way), and instead suggests the spread is due to multiple introductions of related viruses (perhaps moved along by a reservoir species?)
They also note that even for corpses found in the same place, infections from several independent sources may have occurred. For example, they describe a 2002 find of 2 gorillas in the Lossi park, which were found next to each other and likely died around the same time. However, when they examined the GP gene sequences, they were found to differ at 11 bases, suggesting “independent evolution for a minimum of 8 months” based on their molecular clock analysis. Extending this analysis to all viruses, they hypothesize a common ancestor of all Ebola examined in this study existed only ~30 years ago–or right around the time of the first identified human outbreak in the Democratic Republic of Congo (then Zaire).
Though this new research is interesting, it once again highlights the glaring gaps in our knowledge. They conclude:
What remains unclear is how often such introductions have occurred and to what extent transmission among susceptible animal hosts, such as great apes, may have subsequently contributed to the spatial propagation of outbreaks. Similarly, it remains to be resolved whether the temporal-spatial patterns of EBO-Z emergence, which are in many ways suggestive of a spreading process, could be the result of transmission processes in the reservoir species or whether other factors could have generated such patterns.
This research and the previous transmission paper they build on are starting to plug some holes, as did the discovery of the virus in fruit bats, long thought to be potential reservoirs or carriers of Ebola. It’s still baby steps for now, but at least it’s progress toward a better understanding of this still-mysterious pathogen.
Image from http://www.pnas.org/content/vol104/issue43/images/large/zpq0410779330003.jpeg