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Interaction of C1 with HIV-1
N M Thielens1, I M Bally, C F Ebenbichler
1Institut de Biologie Structurale, Laboratire d'Enzymologie Moleculaire, Grenoble, France.
Behring Institute Mitteilungen
|December 1, 1993
Summary
Human immunodeficiency virus type 1 (HIV-1) activates the complement system independently of antibodies. This interaction involves direct binding between the C1q protein and the viral glycoprotein 41 (gp41).
Area of Science:
- Immunology
- Virology
- Complement System
Background:
- Animal retroviruses are lysed by human complement, but Human Immunodeficiency Virus type 1 (HIV-1) is resistant.
- HIV-1 can activate the classical complement pathway without the need for antibodies.
Purpose of the Study:
- To investigate the mechanism by which HIV-1 activates the complement system.
- To identify the specific molecular interactions between HIV-1 and complement component C1q.
Main Methods:
- Activation of reconstituted C1 complex by HIV-1.
- Direct interaction studies between C1q and viral glycoprotein 41 (gp41).
- Utilized C1q fragments and synthetic peptides to map interaction sites.
Main Results:
- HIV-1 directly activates the C1 complex, a key component of the classical complement pathway.
- The interaction involves direct binding between C1q and the external region of gp41.
- Identified specific interaction sites on both C1q (between collagen-like and globular regions) and gp41 (residues 601-613).
Conclusions:
- HIV-1 activates the complement system via direct interaction of C1q with viral gp41, independent of antibodies.
- The identified interaction site on gp41 is within the immunodominant domain and shows homology with HIV-2.
- This interaction provides a novel mechanism for complement activation by enveloped viruses.