The H7N9 Reassortment – Credit Eurosurveillance
# 7212
Two weeks ago, in Eurosurveillance: Sequence Analysis Of H7N9 Suggests `Widespread Circulation’, we looked at research that examined 7 early H7N9 virus samples collected in China’s outbreak and calculated the genetic distance between them.
Simply put, the genetic distance is the accumulated genetic difference between species or between different samples taken within a species.
We know that viruses circulating in the wild pick up mutations at a roughly determinable rate. Once you figure out that rate (it varies among viruses), you can compare two similar viruses, and count the number differences between them.
With that information you can get an idea of how long it has been since their tMRCA (Time To Most Recent Common Ancestor).
The Eurosurveillance study (above) – which utilized mutation rates from two previous H7 outbreaks (in 1999 and 2003) – calculated that H7N9 may have been widely circulating for months before it was finally detected.
But, in exactly what host, remains a subject of debate.
Today the Lancet has the most complete phylogenic analysis of the H7N9 virus to date, that not only suggests this virus evolved through multiple reassortments (likely involving wild birds -> wild ducks -> domesticated ducks -> poultry), it pushes back its estimated tMRCA to roughly January 2012.
doi:10.1016/S0140-6736(13)60938-1
Origin and diversity of novel avian influenza A H7N9 viruses causing human infection: phylogenetic, structural, and coalescent analyses
Di Liu PhD , Weifeng Shi PhD , Yi Shi PhD, Dayan Wang PhD , Haixia Xiao , Wei Li MSc , Yuhai Bi PhD , Ying Wu PhD , Xianbin Li BS, Prof Jinghua Yan PhD , Prof Wenjun Liu PhD, Prof Guoping Zhao PhD , Prof Weizhong Yang MD , Prof Yu Wang MD , Prof Juncai Ma PhD , Prof Yuelong Shu PhD , Prof Fumin Lei PhD , Prof George F Gao DPhil
Summary
Background
On March 30, 2013, a novel avian influenza A H7N9 virus that infects human beings was identified. This virus had been detected in six provinces and municipal cities in China as of April 18, 2013. We correlated genomic sequences from avian influenza viruses with ecological information and did phylogenetic and coalescent analyses to extrapolate the potential origins of the virus and possible routes of reassortment events.
<SNIP>
Findings
The novel avian influenza A H7N9 virus originated from multiple reassortment events. The HA gene might have originated from avian influenza viruses of duck origin, and the NA gene might have transferred from migratory birds infected with avian influenza viruses along the east Asian flyway. The six internal genes of this virus probably originated from two different groups of H9N2 avian influenza viruses, which were isolated from chickens. Detailed analyses also showed that ducks and chickens probably acted as the intermediate hosts leading to the emergence of this virulent H7N9 virus. Genotypic and potential phenotypic differences imply that the isolates causing this outbreak form two separate subclades.
Interpretation
The novel avian influenza A H7N9 virus might have evolved from at least four origins. Diversity among isolates implies that the H7N9 virus has evolved into at least two different lineages. Unknown intermediate hosts involved might be implicated, extensive global surveillance is needed, and domestic-poultry-to-person transmission should be closely watched in the future.
There is a lot here to digest (and I’ve only hit the highlights), so follow the link to read this paper in its entirety (free registration req.).
There also remains a lot we don’t know about this virus, including where it spends its time when its not infecting people. While linked to poultry exposure, questions remain over exactly what host (or hosts) are silently carrying this virus and giving it to humans.
The authors conclude by writing:
. . . on the basis of available evidence, we believe that the novel avian influenza A H7N9 virus was a multiple reassortant. The HA and NA genes might originate from duck avian influenza viruses, which might have obtained the viral genes from migratory birds a year previously, whereas the internal genes might come from chicken avian influenza viruses. We believe that the estimated times to most recent common ancestor for the eight genomic fragments and the frequent poultry transportation in China account for the increased number of confirmed sporadic cases of human infection. In particular, this novel H7N9 virus has diversified into different lineages since its emergence several months ago.