Influenza A(H7N9) virus infects cells from the upper and lower respiratory tract...

Chan and colleagues from the University of Hong Kong (HKU) used tissue taken from (explanted) different parts of the conducting airways and respiratory epithelium to demonstrate the ability of H7N9 (A/Shanghai/1/2013 [Sh1],  A/Shanghai/2/2013 [Sh2] and duck) to replicate in different regions and how well it does that compared to highly pathogenic avian influenza (HPAI) A/H5N1,  and HPAI A/H7N7 and pandemic human A/H1N1.

Some key findings...

• Bronchus, lung nasopharyngeal and tonsil tissues were stained using an antibody to influenza nucleoprotein
• Lung tissue growth
• A/Shanghai/1/2013 > A/Shanghai/2/2013
• A/Shanghai > H5N1
• A/Shanghai/1/2013 > H1N1pdm
• Duck/H7N9 did not replicate
• A/Shanghai/1/2013 > NL/219/H7N7 > H5N1
• Bronchus tissue growth
• A/Shanghai/1/2013 similar to A/Shanghai/2/2013
• A/Shanghai > H5N1
• A/Shanghai similar to H1N1pdm
• Duck/H7N9 did not replicate
• A/Shanghai/1/2013 > NL/219/H7N7 > H5N1
• Nasopharyngeal tissue (33° C) growth
• A/Shanghai/2/2013 replicated
• Primary human pneumocyte growth
• A/Shanghai/1/2013 similar to A/Shanghai/2/2013 but > H5N1 and H1N1pdm
• cDNA PCR was used to gauge the changes in mRNA expression of a range of genes related to interferon (IFN) and IFN signalling, after infection of peripheral blood  monocyte-derived macrophages.
• A/Shanghai upregulated MX1, ISG15, IFI35, IFI44, IFIH1 and OAS1
• Compared to H1N1pdm, A/Shanghai more strongly upregulated IL20RB, IFNAR1, IL20RA, IL22RA2, IL2RB, IL9R and IRF4
• Compared to H1N1pdm, A/Shanghai more strongly downregulated IL10RB and IL4R
• H5N1 & A/Shanghai upregulated IFNβ, IL29, CCL5 and CXCL10 >H1N1pdm
• A/Shanghai upregulated FNβ, IL29, CCL5 < H5N1

The cytokine PCR studies revealed an inflammatory potential between H1N1pdm (milder inflammation) and H5N1 (stronger inflammation).

Understanding which cells and tissues the virus grows in provides some clues as to what to expect from this version of H7N9 in terms of how easily it could be spread and how easily our upper airway tissues (the point of likely first contact with virus) they are to support an animal virus, thus providing a mechanism for animal to human transmission.

The team concluded that Shanghai 2/2013-like H7N9 viruses are well suited to infecting humans and that their major role in disease may not be as relatively strong initiators of inflammation as much their initiation of inflammation in the lower airways.

As Zhu and colleagues previously described, Shanghai 2/2013 also hosted infection in 2/3 ferrets who developed antibodies after airborne exposure to an infected ferret. 

Yet more evidence that H7N9 has the right stuff to cause human harm via attack of the lower airways. 

I still wonder whether it starts off down there - being inhaled as small particle aerosols - or whether it ends up there after establishing itself in the upper airways?