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Since it first emerged as a human health threat in the spring of 2013 H7N9 has undergone constant evolution, spawning dozens of genotypes spread across two major lineages, and even spinning off an HPAI version last winter.
Like its HPAI H5 cousins, H7N9 is extremely promiscuous, and reassorts easily with a number of other avian subtypes.While H7N9 has yet to achieve efficient or sustained human to human transmissibility, we've watched it make incremental and worrisome steps towards a more mammalian adapted virus over the past 5 years. A few recent blogs include:
PLoS Pathogens: Three Mutations Switch H7N9 To Human-type Receptor SpecificityWhile reassortment can introduce large, abrupt changes to an influenza virus, host adaptation can help fine tune the virus for easier infection, carriage, and spread from a specific species. In nature this typically happens through an extended chain of infection, but for research purposes it is often done in the laboratory with animals, or tissue samples.
EID Journal: 2 Expedited HPAI H7N9 Studies
Eurosurveillance: Preliminary Epidemiology & Analysis Of Jiangsu's 5th H7N9 Wave
There are a number hurdles an avian influenza virus must overcome in order to efficiently infect and spread in humans. While not all are known, two of the biggest are: it needs to bind preferentially to human (a2,6) receptor cells and it needs to replicate efficiently at the lower temperatures found in the mammalian respiratory tract.
For a more detailed look, you may wish to revisit Nature Comms: Host Adaptation Of Avian Influenza Viruses.Which brings us to a new study, published this week in Nature, which looks at the host adaptation of H7N9 after multiple passages through lung tissue.
While the virus's replication rate did not increase, it did increase its preference for biding to human receptor cells, albeit at a lower rate (53.4%) than seasonal H1N1 did (76.9%) in a parallel experiment. Additionally, later viruses in the passage study provoked a stronger inflammatory cytokine responses, suggesting increased virulence.
Adaptation of influenza A (H7N9) virus in primary human airway epithelial cells(SNIP)
Daniel Tsung-Ning Huang, Chun-Yi Lu, Ya-Hui Chi, Wan-Ling Li, Luan-Yin Chang, Mei-Ju Lai, Jin-Shing Chen, Wen-Ming Hsu & Li-Min Huang
Scientific Reports 7, Article number: 11300 (2017)
doi:10.1038/s41598-017-10749-5
Received:25 April 2017
Accepted:14 August 2017
Published online:12 September 2017
Abstract
Influenza A (H7N9) is an emerging zoonotic pathogen with pandemic potential. To understand its adaptation capability, we examined the genetic changes and cellular responses following serial infections of A (H7N9) in primary human airway epithelial cells (hAECs).
After 35 serial passages, six amino acid mutations were found, i.e. HA (R54G, T160A, Q226L, H3 numbering), NA (K289R, or K292R for N2 numbering), NP (V363V/I) and PB2 (L/R332R). The mutations in HA enabled A(H7N9) virus to bind with higher affinity (from 39.2% to 53.4%) to sialic acid α2,6-galactose (SAα2,6-Gal) linked receptors. A greater production of proinflammatory cytokines in hAECs was elicited at later passages together with earlier peaking at 24 hours post infection of IL-6, MIP-1α, and MCP-1 levels. Viral replication capacity in hAECs maintained at similar levels throughout the 35 passages.
In conclusion, during the serial infections of hAECs by influenza A(H7N9) virus, enhanced binding of virion to cell receptors with subsequent stronger innate cell response were noted, but no enhancement of viral replication could be observed. This indicates the existence of possible evolutional hurdle for influenza A(H7N9) virus to transmit efficiently from human to human.
Conclusions
Six amino acid mutations were found in A(H7N9) virus during the process of adapting to human cells, including three in HA (R54G, T160A, Q226L, H3 numbering), one in NA (K289R, or K292R for N2 numbering), one in NP (V363V/I), and one in PB2(L/R332R). Our findings showcase the extent of influenza A (H7N9) virus adaptation in human cells and can provide information for the design of vaccine and management of potential outbreak. The adapted virus can bind better to human receptor and has the potential to cause more severe diseases. However, it still cannot replicate efficiently.
(Continue . . . )Of note, this study was submitted last April, and completed before last year's record H7N9 outbreak and the emergence of an HPAI variant. The study used a relatively early Pearl River Delta version of the virus, imported to Taiwan in 2013 (A/Taiwan/1/2013(H7N9)).
The CDC's IRAT system now ranks the newly emerged Yangtze River Delta lineage as being slightly more worrying than the original Pearl River Delta Lineage (see Updating the CDC's IRAT (Influenza Risk Assessment Tool) Rankings), although both sit atop their list of viruses with the greatest pandemic potential.
