Human and avian influenza viruses target different cells in the lower respiratory tract of humans and other mammals

Researchers have identified which sites and cell types within the respiratory tract are targeted by human versus avian influenza viruses, providing valuable insights into the pathogenesis of these divergent diseases.

The report by van Riel et al, “Human and avian influenza viruses target different cells in the lower respiratory tract of humans and other mammals,” appears in the October issue of The American Journal of Pathology and is accompanied by a commentary and highlighted on the cover.

Differences in cellular expression of target molecules correspond to host specificity of influenza viruses. They also define which organs or tissues are infected within the host. For example, highly pathogenic H5N1 avian influenza virus targets cells deep within the lower respiratory tract whereas human influenza virus is thought to target cells of the upper respiratory tract, including the trachea.

To better elucidate the differences between low and highly pathogenic avian influenza virus versus human influenza virus, researchers led by Dr. Thijs Kuiken of Erasmus MC, Rotterdam, The Netherlands, used a technique called virus histochemistry. This method examines the attachment pattern of influenza virus to isolated respiratory tissues, thus identifying the cells targeted by the virus.

When human viruses were tested, both attached strongly to the trachea and bronchi, but virus binding to the bronchioles and alveoli (deeper within the lung) was less abundant in comparison. In contrast, viral attachment of avian viruses was rare in the trachea but more abundant in the bronchioles and alveoli. Further, the cellular targets in the alveoli also differed: human virus preferred type I pneumocytes whereas avian virus bound type II pneumocytes and alveolar macrophages. Interestingly, low and highly pathogenic avian influenza viruses attached to the same cell types, demonstrating that factors other than binding ability must contribute to the pathogenicity.

These data are consistent with the differences in human disease presentation, with human influenza causing tracheobronchitis and highly pathogenic avian influenza causing severe pneumonia. But which animal models are the best for studying the disease in humans" To answer this question, the authors next assessed the pattern of virus attachment in animal models used for influenza studies. Of several mammals tested, ferrets, cats, and pigs most closely resembled the human patterns of virus attachment for avian influenza viruses, thus demonstrating their usefulness as models of infection and disease.

These studies “improve our understanding of the pathogenesis of human respiratory tract disease from both human and avian influenza A virus infection,” state the authors. Combined with the results obtained with different animal models, they may lead to a better understanding of the factors that are critical for virus binding and infection, enabling the future development and testing of feasible control strategies.