Wednesday, October 09, 2013

mBio: H7N9 Naturally Adapted For Efficient Growth in Human Lung Tissue




# 7844



Although we’ve not seen a human case of H7N9 in more than two months, the results of research over the summer continues to point towards this emerging avian influenza virus as being unusually well-adapted to mammals.  A few examples include:


Nature: Limited Airborne Transmission Of H7N9 Between Ferrets
BMJ: `Probable Person-to-Person Transmission’ Of H7N9
Lancet: Tropism Of H7N9 In the Human Respiratory Tract
Science: H7N9 Transmissibility Study In Ferrets


Yesterday the open-access journal mBio published another study,  where researchers conducted in vitro studies – using human (A549) lung tissue and canine (MDCK) Kidney cells – on an H7N9 isolate (A/Anhui/1/2013) collected from a fatal human infection, and two low-pathogenic avian H7 subtype viruses.


Researchers evaluated and compared the replication, tropism, and cytokine induction of all three viruses. They found  the A/Anhui/1/2013 (H7N9) virus was already remarkably well adapted to replicate and infect human lung tissue. 

Additionally, A/H7N9’s NS1 protein suppressed (compared to the other H7 viruses tested) the natural cellular production of beta interferon (IFN-β), an antiviral produced in response to the presence of pathogens like viruses and bacteria.


First, a link to the study, and some excerpts, after which I’ll have more.


The Novel Human Influenza A(H7N9) Virus Is Naturally Adapted to Efficient Growth in Human Lung Tissue

Jessica Knepper, Kristina L. Schierhorn, Anne Becher, Matthias Budt, Mario Tönnies, Torsten T. Bauer, Paul Schneider, Jens Neudecker, Jens C. Rückert, Achim D. Gruber, Norbert Suttorp, Brunhilde Schweiger, Stefan Hippenstiel, Andreas C. Hocke, Thorsten Wolff



. . .  The A(H7N9) patient isolate replicated similarly well as a seasonal IAV in explanted human lung tissue, whereas avian H7 subtype viruses propagated poorly. Interestingly, the avian H7 strains provoked a strong antiviral type I interferon (IFN-I) response, whereas the A(H7N9) virus induced only low IFN levels. Nevertheless, all viruses analyzed were detected predominantly in type II pneumocytes, indicating that the A(H7N9) virus does not differ in its cellular tropism from other avian or human influenza viruses. Tissue culture-based studies suggested that the low induction of the IFN-β promoter correlated with an efficient suppression by the viral NS1 protein. These findings demonstrate that the zoonotic A(H7N9) virus is unusually well adapted to efficient propagation in human alveolar tissue, which most likely contributes to the severity of lower respiratory tract disease seen in many patients.

IMPORTANCE Humans are usually not infected by avian influenza A viruses (IAV), but this large group of viruses contributes to the emergence of human pandemic strains. Transmission of virulent avian IAV to humans is therefore an alarming event that requires assessment of the biology as well as pathogenic and pandemic potentials of the viruses in clinically relevant models. Here, we demonstrate that an early virus isolate from the recent A(H7N9) outbreak in Eastern China replicated as efficiently as human-adapted IAV in explanted human lung tissue, whereas avian H7 subtype viruses were unable to propagate. Robust replication of the H7N9 strain correlated with a low induction of antiviral beta interferon (IFN-β), and cell-based studies indicated that this is due to efficient suppression of the IFN response by the viral NS1 protein. Thus, explanted human lung tissue appears to be a useful experimental model to explore the determinants facilitating cross-species transmission of the H7N9 virus to humans.

(Continue . . . )


For more detail, including methods and materials, you will want to read the entire study.


While scientists know there are many types of viruses that could potentially cause a pandemic, influenza viruses – due to their ability to spread rapidly (including from carriers who are pre-symptomatic or asymptomatic), and to cause severe disease  – are the ones that keep most researchers up at night. They have a long history of causing human misery and death.


Although the news of new cases in China has been absent since early August, concerns run high that the virus will reappear this winter, or in the spring (see  FAO Warns On Bird Flu).  With temperatures dropping, and respiratory infections rising, the Chinese public health authority has already stepped up hospital surveillance for this virus (see Chinese CDC: Be Alert For H7N9).


Last week, just before the government shutdown, the CDC issued two new guidance docs on H7N9 (see H7N9: CDC Guidance On Antiviral Chemoprophylaxis & H7N9: Updated CDC Guidance For Antiviral Treatment).

The saving grace with H7N9, at least so far, is that it hasn’t demonstrated the ability spread efficiently in the human population.

Last week, in BMC: Estimating The Transmission Potential Of H7N9, we saw an encouraging study that found the virus’s R0 (R naught) or Basic Reproductive Number, was well below 1.0 last spring,  suggesting this virus doesn’t yet possess enough `legs’ to spark a major epidemic.


The concern, of course, is that influenza viruses are constantly changing, and so what was true about the virus last spring may not hold true this winter or next spring.


So we watch and we prepare (see Pandemic Preparedness: Taking Our Cue From The Experts) – not because we are convinced that H7N9 will spark the next pandemic.  It could, after all , fade back into the woodwork or simply simmer ominously for years like its H5 cousin.

We pay attention because – just like with MERS-CoV and H5N1 -  we know that it could.