Lung Epithelial TLR7 is a Factor in Viral Replication and Pathogenesis

Lung infections by viruses such as RSV and influenza are the primary causes of illness and death among infants and the elderly. The mechanisms by which these viruses interact with the immune system are not fully understood. This study reveals that ERK MAP kinase signaling, initiated by TLR7 detecting viral RNA, plays a crucial role in the replication of RSV and influenza in bronchial epithelial cells.

TLR7, a pattern recognition receptor, binds to single-stranded RNA viral intermediates in late endosomes. The virus detects and signals through TLR7, leading to the activation of ERK MAP kinase, which in turn promotes viral replication. However, this mechanism is not effective against HPIV3. Blocking TLR7 binding or downstream signaling reduced RSV and influenza replication without affecting HPIV3.

The study also found that RSV viral loads were higher in females than males, likely due to higher expression of the TLR7 gene in females. Mice with a gain of function in TLR7 exhibited increased RSV replication and markers of RSV-associated disease, such as eosinophils and Th2 cells. In conclusion, TLR7, expressed in human lung BECs, acts as a factor in RSV and influenza replication and disease pathogenesis, contributing to sex disparities in viral disease.