Opposing roles of ACE2 and TMPRSS2 in IBV Beaudette infection

Infectious bronchitis virus (IBV) is a significant concern for the poultry industry due to its economic impact. This virus employs sialic acids and heparan sulfate for its cellular attachment, but the specific host proteins involved in its infection are not well understood. A recent study delved into the roles of two host proteins, angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), during the infection caused by the IBV Beaudette (IBV BD) strain.

The researchers found that inhibiting ACE2 in DF-1 cells reduced IBV replication, but reintroducing ACE2 restored the virus's ability to infect the cells. Moreover, increasing ACE2 expression boosted IBV infection in DF-1 and primary chicken embryo kidney cells, suggesting that chicken ACE2 acts as a proviral host factor. On the other hand, TMPRSS2 played a different role in IBV BD infection.

Its absence in DF-1 cells led to a significant increase in infection, while pharmacological inhibition of TMPRSS2 also enhanced infection in DF-1 and Vero cells.

Further investigation through RNA sequencing revealed that alterations in lipid metabolism and membrane-related processes occurred following TMPRSS2 knockout and pharmacological inhibition. These findings underscore the contrasting roles of ACE2 and TMPRSS2 in the IBV BD infection process. The study emphasizes the combined influence of proviral host factors, protease activity, and the cellular membrane environment on gammacoronavirus infections.