Researchers have discovered that the influenza D virus-primarily found in cattle and swine-can efficiently infect human respiratory cells while largely evading early immune detection. The findings raise concerns the virus may spill over into humans with only minimal evolutionary changes.
Using advanced laboratory models, including lung epithelial cells and precision-cut lung tissue samples, scientists tested multiple influenza D isolates collected from livestock between 2011 and 2020. The virus replicated effectively in human-derived tissues, in some cases matching levels seen with seasonal human influenza A.
A key finding: influenza D triggers a weak early immune response in human respiratory cells. It showed reduced activation of interferon signaling pathways, which normally help detect and fight viral infections. This resulted in lower production of antiviral signals compared to human influenza viruses.
However, when an antiviral state was artificially induced, the virus became more vulnerable-suggesting it is not fully resistant to immune defenses but may initially evade detection.
The study highlights that only small genetic changes might be needed for sustained transmission in humans, though this has not yet been observed. People in regular contact with cattle and swine may already be exposed, as suggested by antibody responses in agricultural workers.
The research underscores the need for enhanced surveillance at the animal-human interface to better assess pandemic potential before widespread adaptation occurs.