Wave-Like Spread of Ebola Zaire

Abstract

In the past decade the Zaire strain of Ebola virus (ZEBOV) has emerged repeatedly into human populations in central Africa and caused massive die-offs of gorillas and chimpanzees. We tested the view that emergence events are independent and caused by ZEBOV variants that have been long resident at each locality. Phylogenetic analyses place the earliest known outbreak at Yambuku, Democratic Republic of Congo, very near to the root of the ZEBOV tree, suggesting that viruses causing all other known outbreaks evolved from a Yambuku-like virus after 1976. The tendency for earlier outbreaks to be directly ancestral to later outbreaks suggests that outbreaks are epidemiologically linked and may have occurred at the front of an advancing wave. While the ladder-like phylogenetic structure could also bear the signature of positive selection, our statistical power is too weak to reach a conclusion in this regard. Distances among outbreaks indicate a spread rate of about 50 km per year that remains consistent across spatial scales. Viral evolution is clocklike, and sequences show a high level of small-scale spatial structure. Genetic similarity decays with distance at roughly the same rate at all spatial scales. Our analyses suggest that ZEBOV has recently spread across the region rather than being long persistent at each outbreak locality. Controlling the impact of Ebola on wild apes and human populations may be more feasible than previously recognized.

Isolates of Zaire ebolavirus from wild apes reveal genetic lineage and recombinants

“…However, our new genetic data reveal that the more recent outbreaks are not caused by genetic descendents of previously emerging viruses, as seen in previous data, but instead involve a genetically different type of ZEBOV. Thus, because outbreaks do not appear to be epidemiologically linked in a consistent fashion, these findings challenge the notion of ZEBOV emergence in recent years being driven by a single viral lineage spreading through the affected area of Gabon/RC (9).…”

“…This finding suggests the existence of some underlying ecological factor that connects all outbreaks regardless of the genetic type of virus involved. Movement and contact processes among animals involving either reservoir or susceptible species, or both, may be potential mechanisms for this (8,9).…”

“…This tree topology, combined with the temporal-spatial pattern of ZEBOV emergence over the last two decades, led some authors to suggest that outbreaks are epidemiologically linked and occur at the front of an advancing wave that emerged ca. 1976 in the Democratic Republic of the Congo (9). However, the identification of multiple strains during the 2001 Gabon/ Republic of the Congo (RC) outbreak led other authors to deduce that ZEBOV repeatedly and independently spilled over from the reservoir species (most likely bats) (10) into wildlife and human populations (3).…”

Unifying the spatial population dynamics and molecular evolution of epidemic rabies virus

“…The detection and analysis of molecular evolutionary change in RNA viral populations will be a critical tool in establishing these linkages, because evolutionary and ecological dynamics in these organisms occur on the same timescale. Statistical analysis of sequence evolution in space and time has been successfully used to detect wave-like patterns of spread in the Central African emergence of the Ebola Zaire virus variant (35) and the rapid spread of both European Bat Lyssaviruses 1 and 2 throughout Western Europe (E. Holmes, personal communication). We suspect that, as more gene sequence information becomes readily available, the use of integrated approaches such as the geographical analysis of sequence variants will become an indispensable aid in understanding patterns of disease emergence.…”

Molecular Evolution of Viruses of the Family Filoviridae Based on 97 Whole-Genome Sequences

“…Further confusing the issue, some authors have presented data indicating that viruses of at least one filovirus species (Zaire ebolavirus) share a most recent common ancestor (MRCA) in the very recent past (29)(30)(31)(32). Previous studies have attempted to estimate rates of nonsynonymous substitutions and divergence times among viruses within the Filoviridae; however, most have been limited in terms of sample size (25) or have examined only a single species, in particular, Zaire ebolavirus (29,31,32). Here, we perform detailed Bayesian coalescent phylogenetic analyses on 97 virus whole-genome sequences (55 of which are newly reported here) to comprehensively examine the evolutionary rates of the filoviruses and estimate dates of common ancestry within this family.…”