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Epstein-Barr virus regulates activation and processing of the third component of complement
C Mold1, B M Bradt, G R Nemerow
1Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.
The Journal of Experimental Medicine
|September 1, 1988
Summary
Epstein-Barr virus (EBV) demonstrates complement regulatory activities, acting as a cofactor for factor I to cleave C3 and C4. These functions, distinct from CR1, likely help EBV evade host defenses.
Area of Science:
- Immunology
- Virology
- Complement System
Background:
- The Epstein-Barr virus (EBV) is a human herpesvirus known to infect B cells and epithelial cells.
- The complement system is a crucial part of innate immunity that can be activated by pathogens, including viruses.
- EBV's interaction with the complement system is not fully understood, particularly its potential to evade immune responses.
Purpose of the Study:
- To investigate the complement regulatory activities of purified Epstein-Barr virus (EBV).
- To determine if EBV possesses cofactor activity for factor I-mediated cleavage of complement proteins C3 and C4.
- To differentiate EBV's complement regulatory functions from those of human complement receptor 1 (CR1).
Main Methods:
- Incubation of purified EBV with serum to analyze complement C3 cleavage fragments.
- Testing purified EBV for factor I cofactor activity in the breakdown of C3b and C4b.
- Assessing EBV's effect on the decay of alternative and classical pathway C3 convertases.
- Utilizing functional assays, immunological detection, and monoclonal antibodies to rule out CR1 involvement.
Main Results:
- Purified EBV exhibited cofactor activity for factor I, mediating the breakdown of C3b to iC3b, C3c, and C3dg, and C4b to iC4b, C4c, and C4d.
- EBV accelerated the decay of the alternative pathway C3 convertase but did not affect the classical pathway C3 convertase.
- Evidence strongly excluded CR1 as the source of these activities, as EBV lacked CR1-specific functions like rosetting and did not bind CR1 antibodies.
Conclusions:
- Purified EBV possesses multiple complement regulatory activities, including factor I cofactor function and alternative pathway C3 convertase decay acceleration.
- These activities are distinct from those of CR1 and represent novel functions for EBV.
- These EBV-mediated complement evasion mechanisms likely contribute to the virus's survival and pathogenesis by subverting host immune defenses.