Abstract
The complement system has developed different strategies to clear infections by several effector mechanisms, such as opsonization, which supports phagocytosis, attracting immune cells by C3 and C5 cleavage products, or direct killing of pathogens by the formation of the membrane attack complex (MAC). As the Zika virus (ZIKV) activates the classical complement pathway and thus has to avoid clearance by the complement system, we analyzed putative viral escape mechanisms, which limit virolysis. We identified binding of the recombinant viral envelope E protein to components of the terminal pathway complement (C5b6, C7, C8, and C9) by ELISA. Western blot analyses revealed that ZIKV E protein interfered with the polymerization of C9, induced on cellular surfaces, either by purified terminal complement proteins or by normal human serum (NHS) as a source of the complement. Further, the hemolytic activity of NHS was significantly reduced in the presence of the recombinant E protein or entire viral particles. This data indicates that ZIKV reduces MAC formation and complement-mediated lysis by binding terminal complement proteins to the viral E protein.
Highlights
The complement system is an effective arm of innate immunity
As Zika virus (ZIKV) activates the classical pathway of complement, we were interested in whether the virus adapted means to reduce virolysis
Viral particles interfere with membrane attack complex (MAC) formation
Summary
The complement system is an effective arm of innate immunity. It is a family of membraneanchored and soluble proteins circulating in the blood in their inactive form [1, 2]. All three pathways result in C3 activation and the formation of C3 convertases, and they merge in the induction of the terminal pathway. This final step generates the membrane attack complex (MAC) consisting of C5b-8 and 12–18 molecules of C9, which makes a pore on the cell surface to kill pathogens or infected cells [1, 2]. To avoid destruction by the complement system, viruses have acquired strategies that can be condensed to a few successful mechanisms: 1) inactivation by enzymatic
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
