Human immunodeficiency virus type 1 induces expression of complement factors in human astrocytes

Since the brain is separated from the blood immune system by a tight barrie r, the brain-resident complement system may represent a central player in t he immune defense of this compartment against human immunodeficiency virus (HIV). Chronic complement activation, however, may participate in HIV-assoc iated neurodegeneration. Since the level of complement factors in the cereb rospinal fluid is known to be elevated in AIDS-associated neurological diso rders, we evaluated the effect of HIV type 1 (HIV-1) on the complement synt hesis of brain astrocytes. Incubation of different astrocytic cell lines an d primary astrocytes with HIV-1 induced a marked upregulation of the expres sion of the complement factors C2 and C3. The synthesis of other secreted o r membrane-bound complement proteins was not found to be altered. The enhan cement of C3 production was measured both on the mRNA level and as secreted protein in the culture supernatants. HIV-1 laboratory strains as well as p rimary isolates were capable of inducing C3 production with varied effectiv eness. The usage of viral coreceptors by HIV-1 was proved to be a prerequis ite for the upregulation of C3 synthesis, which was modulated by the simult aneous addition of cytokines. The C3 protein which is secreted after incuba tion of the cells with HIV was shown to be biologically active as it can pa rticipate in the complement cascade.