By Amesh A. Adalja, MD, FACP, May 6, 2013
The tide of reported cases of H7N9 in China seems to have slowed, possibly because the live poultry market in Shanghai was closed last month. The current case count is 130, and all cases have been linked to mainland China. There have been 31 deaths to date. Study of the virus itself has now provided some information about how H7N9 may behave in the future.
The PB2 gene in the H7N9 virus facilitates viral reproduction. Of the 8 human cases in which the PB2 gene has been sequenced, 8 have the E627K, D701N mutations, which are considered adaptations to humans. By contrast, none of the avian H7N9 isolates with available genetic sequences harbor this mutation. The presence of mutations that are adaptations to human hosts is leading researchers to conclude that the virus may be spreading from person to person because the mutations did not arise in birds.
Additionally, as reported in the medical journal, Lancet, it appears that the H7N9 virus that is infecting humans is the product of reassortment of 4 other influenza viruses, with 1 gene of the new virus coming from ducks, another from migratory birds, and the last 2 genes coming from 2 different H9N2 bird viruses. Reassortment is the process by which influenza viruses exchange segments of genes among themselves, creating new hybrid viruses. Additional genetic sequence analysis also points to the possibility that 2 human strains of the virus are spreading. If that is the case, it would suggest that the virus has been infecting humans for some time and has mutated to adapt to human hosts.
The Shanghai Public Health Clinical Center has published clinical details on 4 of its patients with H7N9 infection, all of whom had been exposed to poultry, the presumed source of their infections. One important detail in this report is that all 4 patients were treated with the antiviral oseltamivir, sometimes with double the usual treatment dose. However, the time to start of treatment ranged from 4 to 16 days after the onset of illness. Oseltamivir is most effective when given soon after the onset of symptoms, so it’s not clear that antiviral treatment had any benefit for these 4 patients.
The finding that human isolates contain specific human-adapting mutations that are not found in bird isolates is worrisome. It points to the possibility that the virus is spreading within human populations at a rate higher than what has been reported since, to date, it has been thought that human transmission is not occurring. Because these mutations are not found in bird isolates, human-to-human spread remains the most likely explanation.
Another hypothesis, although less likely, is that the virus is being spread to humans from another animal species that has not yet been identified. Finally, it could be that the mutations are occurring during reproduction of the virus within humans.
As a greater quantity of genetic sequence data is released, the comparison of isolates from bids and humans with varying severity of illness will be essential to gauge the potential for spread of this virus.
1.Evidence for sustained human H7N9 transmission. April 30, 2013. Recombinomics, Inc., Web site. http://www.recombinomics.com/News/04301301/H7N9_Sustained.html. Accessed May 6, 2013.
2.Liu D, Shi W, Shi Y, et al. Origin and diversity of novel avian influenza A H7N9 causing human infection: phylogenetic, structural, and coalescent analyses. Lancet. May 1, 2013. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2960938-1/fulltext?_eventId=login#fig2. Accessed May 6, 2013.
3.Lu S, Zheng Y, Li T, et al. Clinical findings for early human cases of influenza A(H7N9) virus infection, Shanghai, China. Emerg Infect Dis. 2013.