Proteolytic Processing of Hendra Virus Fusion Protein in Cells of the Bat Reservoir Host

Abstract

Hendra and Nipah are recently emerged, zoonotic paramyxoviruses with high mortality rates. While the majority of paramyxovirus fusion (F) proteins are proteolytically activated by the host protease furin, Henipavirus F proteins utilize the protease cathepsin L. The primary natural reservoir of Henipaviruses is fruit bats. Interestingly, fruit bats act as reservoirs for SARS‐like coronavirus and Ebola virus, both of which use cathepsins during their life cycles. We analyzed proteolytic processing of viral glycoproteins in recently generated cell lines from the fruit bats Pteropus alecto and Rousettus aegyptus. Both the cathepsin‐dependent Hendra virus F and the furin‐dependent parainfluenza virus 5 F proteins were properly cleaved, suggesting that furin and cathepsin‐like proteases function in these cells. Syncytia formation was observed with expression of either F protein, confirming that proteolytic activation resulted in fusogenic molecules. Addition of cathepsin L inhibitors inhibited Hendra F, but not PIV5 F cleavage in all cell types. There results demonstrate that proteolytic activation of Henipavirus F proteins by cathepsin is not due to lack of furin‐like proteases in Pteropus bat cells.This work was supported by NIAID/NIH grant R01AI051517 and NIH grant #U54 AI057157 from the Southeastern Regional Center of Excellence for Emerging Infections and Biodefense.