A novel factor I activity in Nipah virus inhibits human complement pathways through cleavage of C3b
Complement is an innate immune system that most animal viruses must face during natural infections. Given that replication and dissemination of the highly pathogenic Nipah virus (NiV) include exposure to environments rich in complement factors, we tested the in vitro sensitivity of NiV to complement-mediated neutralization. Here we show that NiV was completely resistant to in vitro neutralization by normal human serum (NHS). Treatment of purified NiV with NHS activated complement pathways, but there was very little C3 deposition on virus particles. In in vitro reconstitution experiments, NiV particles provided timeand dose-dependent factor I-like protease activity capable of cleaving C3b into inactive C3b (iC3b). NiV-dependent inactivation of C3b only occurred with the cofactors factor H and soluble CR1 but not with CD46. Purified NiV particles did not support C4b cleavage. Electron microscopy of purified NiV particles showed immunogold labeling with anti-factor I antibodies. Our results suggest a novel mechanism by which NiV evades the human complement system through a unique factor I-like activity.
|Persistent URL||dx.doi.org/10.1128/JVI.02427-14, hdl.handle.net/1765/116612|
|Journal||Journal of Virology|
Johnson, J.B. (John B.), Borisevich, V. (Viktoriya), Rockx, B, & Parks, G.D. (Griffith D.). (2015). A novel factor I activity in Nipah virus inhibits human complement pathways through cleavage of C3b. Journal of Virology, 89(2), 989–998. doi:10.1128/JVI.02427-14