Infection of human lung tissue with influenza A and MERS-corona virus

Zoonotic respiratory pathogens like influenza A (IAV) or corona viruses causing epidemic and pandemic outbreaks with high fatality rates frequently stresses public health systems worldwide. It remained an open debate whether the efficiency of viral propagation and disease outcome is determined by differences in the receptor dependent cellular tropism of viral subtypes. For IAV, we have shown that independent of human and avian receptor distribution different types of human, avian, and swine viruses almost exclusively replicate in alveolar type II cells. However, the replication rates of the strains showed significant differences corresponding to clinical observations.

At present, a novel avian H7N9 as well as a Middle East respiratory syndrome corona virus (MERS-CoV) originating from bats have been isolated from severely diseased patients with pneumonia and ARDS in Eastern China or the Middle East, respectively. For H7N9 we evaluated replication, tropism and cytokine induction in a human lung organ culture. Again, a strong type II tropism and an efficient replication as for human adapted IAV was found. Moreover, the robust replication correlated with a low induction of antiviral IFN caused by the viral NS1 protein.

For MERS-CoV essential information about virus- and host-dependent disease processes is also still missing. Therefore, we used a BAL sample from an infected patient and human lung tissue to describe replication, tropism, DPP4 receptor expression and alveolar damage. Interestingly, MERS-CoV propagation was as efficient as for highly pathogenic avian H5N1. However, next to type II cells, nearly all cell types of the respiratory tract got infected correlating with the ubiquitous expression of the DPP4 receptor. In the alveolar compartment as well as in BAL, infected cells underwent apoptosis and detached from the alveolar wall which might trigger the acute lung injury. A similar cell lytic infection pattern has also been found for IAV.

Taken together, pathogenic respiratory viruses show distinct types of cellular tropism with an emphasis for type II cells and the postulated receptors seem to be essential for viral entry. However, additional mechanisms like the suppression of anti-viral host responses based on changed genetic viral background seems to be of high importance for determining the disease severity and have to be further elucidated.