The H1N1 flu pandemic of 2009 underscored the importance of the pig population both as a reservoir and a mixing vessel for influenza strains, and provided added impetus for comparing the biology of influenza in human and pig populations.

Examining the susceptibility to infection of pig lung (alveolar) macrophages (AM) and bone marrow-derived macrophages (BMM), we determined that while pig BMM supported productive replication of a human seasonal H3N2 virus strain, pig AM didn’t release functional viral particles. H3N2 did replicate within pig AM as shown by viral nucleoprotein immunostaining, suggesting that it could still hijack and alter the cell biology even though AM do not release functional viral particles. On the other hand, pig AM are resistant to pandemic H1N1 infection, as has been shown for human AM. Therefore, differential susceptibility of lung macrophages to infection could be a determinant of virulence and lung pathology in both humans and pigs.

In parallel, through collaboration with the RIKEN Omics Science Centre in Yokohama, the gene expression responses of human macrophages to flu infection were compared by cap-analysis of gene expression (CAGE). Key insights include an important inter-individual variation in the human response to infection, which can range from varying levels of activation of specific genes to different time courses of activation.

We are currently comparing CAGE data to pig microarray data and contrast in great detail the host response to infection in those immunologically similar organisms. The comparative analysis of human and pig response to influenza is key to understanding how host response is specifically tailored to this infection, as well as defining influenza-specific targets for therapeutic intervention.

(From a conference paper presented at the European Macrophage and Dendritic Cell Society 2012 Meeting, September 1-3, 2012, Debrecen, Hungary)