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Web app for visualizing pathogen evolution
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title: Twenty years of West Nile virus
authors: James Hadfield, Anderson F. Brito, Daniele M. Swetnam, Chantal B.F. Vogels, Ryan E. Tokarz, Kristian G. Andersen, Ryan C. Smith, Trevor Bedford, Nathan D. Grubaugh
date: "June 2019"
dataset: "https://nextstrain.org/WNV/NA?d=map"
abstract: "It has been twenty years since West Nile virus first emerged in the Americas, and since then, little progress has been made to control outbreaks caused by this virus. Using Nextstrain, we investigate the emergence of West Nile virus in the United States, followed by its rapid spread, evolution in a new environment, establishment of endemic transmission, and subsequent international spread."
# [Emergence of an exotic virus](https://nextstrain.org/WNV/NA?c=num_date&dmax=1998-12-01&dmin=1995-11-18&f_country=Israel,USA&d=map)
### When was West Nile virus first introduced?
Genomic investigations revealed that West Nile virus was likely first introduced in the United States 1 year before the outbreak in New York in 1999.
### Where did the virus come from?
Phylogenetic comparisons showed that West Nile virus sequences isolated from New York in 1999 were most closely related to a WNV isolate from Israel, suggesting a potential origin from the Middle East.
### How did it get there?
Although it is impossible to determine exactly how WNV was introduced, human transportation of infected birds or mosquitoes, is the more plausible mechanism for the introduction of WNV from the Middle East into the U.S.
# [Conquering a continent: Part I](nextstrain.org/WNV/NA?animate=1997-12-01,2018-08-27,1,0,30000&c=num_date&d=map&f_country=USA)
You are now seeing a the spread of WNV between 1998 - 2019 as an animation. The color represents the time, starting with blues & greens in the 90s and early 2000s through to oranges & reds in the past decade.
### When did West Nile virus spread to the West Coast?
Based on spatial and phylogenetic data, it is estimated that West Nile virus initially moved at an average dispersal velocity of ~1,000 km/year. The virus likely arrived at the West Coast in 2002 (light blue colored lines), a year before it was detected by local surveillance systems.
# [Conquering a continent: Part II](nextstrain.org/WNV/NA?c=num_date&f_country=USA&d=map)
### What factors aided its rapid spread?
It is likely that a large population of naive and susceptible bird hosts and mosquito vectors already present in the United States helped West Nile virus to quickly spread across the continent despite the varied landscapes that it needed to traverse.
### How did the virus spread rapidly across long distances?
Laboratory, field, and phylogenetic studies support the hypothesis that the long-distance spread of West Nile virus was facilitated by the movement of infected migratory birds; however, it was likely not the only mechanism.
# [Aided by evolution? Part I](https://nextstrain.org/WNV/NA?c=lineage&d=tree)
Looking at the phylogenetic tree, with clades colored by strain (sometimes called genotype).
### Did West Nile virus adapt to a new environment?
The virus genomic data shows that the introduced West Nile virus genotype (termed NY99) was displaced by locally derived genotypes (WN02 and SW03), suggesting that the virus may have undergone adaptive evolution in the United States.
# [Aided by evolution? Part II](https://nextstrain.org/WNV/NA?c=lineage&d=tree&l=clock)
Moving to a root-to-tip plot, where the horizontal axis represents sampling time and the vertical axis represents genomic divergence, we can see a clock-like accumulation of mutations over the past 20 years.
### What was the role of evolution during emergence?
It is hypothesized that adaptation of West Nile virus to mosquitoes in the Americas facilitated its westwardly spread. However, additional studies are required to determine how differences in transmission efficiencies among West Nile virus genotypes can impact spread.
# [Becoming an entrenched virus: part I](https://nextstrain.org/WNV/NA?f_state=NY&d=tree)
We are now looking only at isolates from New York State (purple tips).
### Is West Nile virus a threat every year?
Since its introduction and spread across the continent, cases of West Nile virus are reported annually in the United States. Evidence for endemicity from the genomic data is clear in, for instance, New York, with some local transmission chains (i.e. branches on the phylogenetic tree) persisting for at least 10 years.
# [Becoming an entrenched virus: part II](https://nextstrain.org/WNV/NA?f_state=CA,CO,TX&d=tree)
We now look at samples from California (pink), Texas (Yellow) and Colorado (light pink).
### Are cases evenly distributed throughout the United States?
The majority of cases have occurred in just a handful of states that includes Colorado, California, and Texas. However, the highest incidence of West Nile virus can be found in the Great Plains region of the United States.
### What factors cause these differences in human cases?
Rainfall and temperature have a large impact on West Nile virus intensity from year to year by influencing mosquito and bird populations. Differences in climate and regional ecology shape the resident mosquito and bird populations resulting in distinct transmission networks at the local and regional level.
# [An international concern](https://nextstrain.org/WNV/NA?c=country&f_country=Argentina,Brazil,British-Virgin-Islands,Colombia,Mexico&d=map&r=division)
### Did West Nile virus spread outside of the United States?
The virus genomic data shows that there were multiple, southwards West Nile virus introductions since early stages of outbreak in the United States. Now West Nile virus is endemic in Central America, the Caribbean, South America, as well as several southern Canadian provinces.
### How did it spread across the Americas?
The limited West Nile virus genomic data from the Americas outside of the United States makes it difficult to understand the mechanisms that facilitate its spread. However, some serological evidence from migratory birds suggests that they may be important disseminators of West Nile virus throughout the Americas.
### Why have major human outbreaks not been reported in Latin America?
The apparent lack of large outbreaks in Latin America may be explained by (1) West Nile virus cases being masked or misdiagnosed as other flavivirus infections, or by (2) immune cross-protection provided by other endemic flaviviruses.
# [Future role of genomics](https://nextstrain.org/WNV/NA?c=lineage&d=map&r=division)
### How to fill the gaps?
Significant national investment is required in sustained and collaborative efforts to fill in the many gaps in West Nile virus genomic sampling throughout the country, especially from the last 10 years, to better understand endemic West Nile virus transmission using virus genomics approaches.
### How to control the next outbreak?
Systematically searching for connections among West Nile virus outbreaks around the country may reveal endemic ‘transmission networks’, which could be exploited for control and forecasting purposes. Vector control efforts can be maximized by strategically focusing resources at a precise time and location to limit potential outbreaks.