# 7982
While MERS-CoV has captured most of our attention these past few weeks, we continue to keep a wary eye on the H7N9 avian flu virus in China, which last spring suddenly sprang to the top of our `worry list’. So far, the number of cases reported this fall have been small, but concerns remain that it could return with a vengeance over the winter and spring (see Chinese CDC: Be Alert For H7N9).
Over the summer we’ve seen a parade of studies that have painted this emerging virus as being better suited to mammalian hosts, and possessing greater pandemic potential, than any other avian flu studied to date. A few examples include:
Nature: Limited Airborne Transmission Of H7N9 Between Ferrets
BMJ: `Probable Person-to-Person Transmission’ Of H7N9
Although we normally hear about flu research being conducted on ferrets – due to their human-like response (sneezing, coughing) to influenza infections - in recent years a number of researchers have looked at guinea pigs as alternative mammalian model for influenza studies (see PNAS The guinea pig as a transmission model for human influenza viruses by Peter Palese et al. 2006).
Bouvier and Lowen, in Animal Models for Influenza Virus Pathogenesis and Transmission, describe the advantages of the guinea pig model below:
The strengths of the guinea pig model lie in the natural susceptibility of these animals to human influenza virus isolates, the efficiency with which human strains transmit among guinea pigs and the relative ease of obtaining, housing and working with these animals. The main drawback of the guinea pig model for influenza research is the lack of disease signs exhibited by infected animals.
Earlier this year (see CIDRAP NEWS report Study: Lab-made H5N1-H1N1 viruses spread in guinea pigs) we learned that Chinese scientists had recently used guinea pigs to study reassortant viruses, explaining:
. . . guinea pigs are comparable with ferrets as models of human flu transmission. Although guinea pigs have both avian and mammalian types of airway receptors, flu viruses that bind only to avian receptors (alpha2,3-linked sialic acids) don't spread by respiratory droplets in the animals, they report.
Which brings us to a study, published this week in the Journal of Virology, that looks at how well the newly emerging H7N9 avian flu virus replicates and transmits in guinea pigs.
And the answer . . . pretty darn well.
Jon D. Gabbard, Daniel Dlugolenski, Debby Van Riel, Nicolle Marshall, Summer E. Galloway, Elizabeth W. Howerth, Patricia J. Campbell, Cheryl Jones, Scott Johnson, Lauren Byrd-Leotis, David A. Steinhauer, Thijs Kuiken, S. Mark Tompkins, Ralph Tripp, Anice C. Lowen and John Steel
ABSTRACT
The zoonotic outbreak of H7N9 subtype avian influenza virus that occurred in eastern China in the spring of 2013 resulted in 135 confirmed human cases, 44 of which were lethal. Sequencing of the viral genome revealed a number of molecular signatures associated with virulence or transmission in mammals.
Here we report that, in the guinea pig model, a human isolate of novel H7N9 influenza virus, A/Anhui/1/2013 (An/13), is highly dissimilar to an H7N1 avian isolate and instead behaves similarly to a human seasonal strain in several respects. An/13 was found to have a low 50% infectious dose, grow to high titers in the upper respiratory tract, and transmit efficiently among co-caged guinea pigs.
The pH of fusion of the HA and the binding of virus to fixed guinea pig tissues were also examined. The An/13 HA displayed a relatively elevated pH of fusion characteristic of many avian strains, and An/13 resembled avian viruses in terms of attachment to tissues. One important difference was seen between An/13 and both the H3N2 human and H7N1 avian viruses: when inoculated intranasally at high dose, only the An/13 virus led to productive infection of the lower respiratory tract of guinea pigs.
In sum, An/13 was found to retain fusion and attachment properties of an avian influenza virus but displayed robust growth and contact transmission in the guinea pig model atypical of avian strains and indicative of mammalian adaptation.
The bottom line here is the H7N9 virus behaves more like a humanized flu virus than an avian flu virus in the guinea pig model. And the AN/13 H7N9 virus actually out performed the H3N2 human virus in some respects, traveling more readily from the upper respiratory system to the lower respiratory tract.
This study adds to the growing body of evidence showing that the H7N9 virus is better adapted to mammals than other avian flu strains that we’ve observed. Adaptations, some researchers believe, the virus most likely acquired while inhabiting an (as yet, unidentified) intermediate mammalian host.
Whether this ability means H7N9 will turn into a serious global public health threat, is something we will just have to wait to see. But its ability to infect mammals, `right out of the box’, is impressive.
One of the big unanswered questions regarding this avian virus is: how, and from what reservoir(s), it is spreading?
Poultry and wild birds are immediately suspect, but out of hundreds of thousands of birds tested, only a handful have proven positive (see Poultry Samples Around Dongguan H7N9 Case Test Negative).
Last May, the Lancet published Origin and diversity of novel avian influenza A H7N9 viruses causing human infection: phylogenetic, structural, and coalescent analyses by Liu D et al., which looked at the virus’s genomic sequences, and found:
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.
In recent years we’ve discovered a good many mammalian species are capable of hosting various influenza strains, in addition to humans, swine, and equines. The (formerly) pandemic H1N1 2009 flu virus was documented in turkeys, skunks, ferrets, cats, elephant seals and dogs. While in That Touch Of Mink Flu I wrote about 11 farms in Holstebro, Denmark that were reported to be infected with a variant of the human H3N2 virus.
Less commonly reported - camels, whales and seals have all been shown to be susceptible to influenza viruses (cite Evolution and ecology of influenza A viruses R.G. Webster et al.) In 2012, an avian flu strain was identified in New England seals (see mBio: A Mammalian Adapted H3N8 In Seals).
And last year (see EID Journal: Guinea Pigs As Reservoirs For Influenza by Leyva-Grado VH, Mubareka S, Krammer F, Cárdenas WB, Palese P.), we looked at a serological study that found that Peruvian and Ecuadorian guinea pigs – raised as livestock – are commonly infected by influenza A and B viruses.
Despite finding high seroprevalence results, the authors cautioned:
We did not determine whether guinea pigs are an incidental host for influenza virus infection or, if instead, the virus has been adapted to these animals or if guinea pigs are a natural reservoir for some influenza viruses.
And lastly, in 2010 I wrote a blog entitled Mixing Vessels For Influenza which explored research done by two wildlife disease experts from the San Diego Zoo - Mark Schrenzel and Bruce Rideout – who identified the North American Striped Skunk - along with a handful of other small carnivores - as potential hosts for influenza reassortment.
None of this brings us any closer to knowing what species – other than avian – might be serving as an intermediate host for H7N9.
But it does illustrate that there are a wide range of possibilities that ought to be explored and tested.
