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Cleavage of the complement system C3 component by HIV-1 proteinase
A F Kisselev1, R Mentele, K von der Helm
1Max von Pettenkofer-Institute, Munich, Germany.
Insights
The human immunodeficiency virus proteinase (HIV PR) cleaves complement factor C3 and its C3b fragment. This cleavage mimics natural complement inactivation, suggesting a biological role for HIV PR in this process.
Area of Science:
- Biochemistry
- Immunology
- Virology
Background:
- The complement system is crucial for innate immunity.
- Human immunodeficiency virus proteinase (HIV PR) is essential for viral maturation.
- Complement factor C3 is a central component of the complement cascade.
Purpose of the Study:
- To investigate the in vitro interaction between HIV PR and complement factor C3/C3b.
- To identify the cleavage sites and resulting fragments of C3/C3b by HIV PR.
- To explore the potential biological implications of HIV PR-mediated C3 cleavage in complement inactivation.
Main Methods:
- In vitro enzymatic assays using purified C3 and C3b.
- Analysis of cleavage products by SDS-PAGE.
- Identification of specific cleavage sites within the C3 alpha-chain.
Main Results:
- HIV PR effectively cleaves both C3 and C3b.
- Cleavage occurs at multiple sites in the alpha-chain, generating a 100 kDa fragment from C3 and various fragments from C3b.
- Identified scissile bonds: Ala86-Glu87, Leu310-Leu311, His641-Trp642, and Arg649-Ser650.
- Generated fragments resemble inactive C3 fragments (C3c, C3d).
Conclusions:
- HIV PR possesses enzymatic activity against complement factor C3 and C3b.
- The cleavage pattern suggests HIV PR can functionally inactivate the complement system.
- This interaction may represent a mechanism by which HIV evades host immune responses.
Abstract:
The C3 factor of the complement system and its C3b fragment are cleaved in vitro by the proteinase of the human immunodeficiency virus, type 1 (HIV PR). The cleavage occurs in the alpha-chain of both substrates at multiple sites yielding a 100 kDa fragment of the C3 alpha-chain and multiple fragments of the C3b alpha-chain. The scissile bonds are: Ala86-Glu87, Leu310-Leu311, His641-Trp642 and Arg649-Ser650. The resulting fragments resemble the physiologically occurring inactive fragments of C3: C3c and C3d, suggesting a possible biological role of the HIV-proteinase in the complement inactivation process.