Interaction of the envelope glycoprotein of human immunodeficiency virus with C1q and fibronectin under conditions present in human saliva.
Human saliva has been shown to reduce the infectivity of human immunodeficiency virus (HIV) particles in vitro. The factors in human saliva involved in this inhibition of HIV infectivity are unknown, although the salivary sediment of normal individuals has the major HIV neutralizing activity. Interestingly, the first complement component (C1) has been detected on the surface of the salivary sediment in the whole saliva of normal individuals. At the relatively low ionic strength of saliva, we determined that purified human C1q bound with high affinity to the envelope glycoprotein of HIV. Normally, the interaction of the C1q globular heads with immune complexes causes C1 activation. However, direct interactions between C1 and rgp120 (or rgp160) did not lead to C1 fixation, as determined by hemolytic studies with rate-limiting levels of C1, nor did rgp120 cause C1 activation as determined by activated C1s-mediated C4 conversion in normal human serum. Using ELISA, it was observed that intact C1, with the C1r2C1s2 tetramer associated with the collagen-like stem of C1q, did not bind to immobilized rgp120, whereas free C1q did bind. In addition, digestion of the C1q stem portion with collagenase completely eliminated its binding to rgp120. These findings suggest that the collagen-like stem region of C1q, rather than the globular heads, may participate in the binding to the envelope glycoprotein of HIV. Fibronectin, which is present in submandibular saliva, appeared to bind to rgp120 and to enhance the interaction of C1q with rgp120. It is conceivable that C1q and fibronectin, in binding and sequestering HIV particles (i.e. to the salivary sediment), may play an important role in the reduction of HIV transmission via saliva. Further studies will be needed to test the latter speculation.
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Department of Microbiology and Immunology, Medical University of South Carolina, Charleston 29425-2230.
Boackle
R J
RJ
D015153:Blotting, Western; D003167:Complement Activation; D003172:Complement C1 / Q000494:pharmacology; D015922:Complement C1q / Q000378:metabolism*; D003181:Complement C4 / Q000096:biosynthesis; D015941:Complement Hemolytic Activity Assay; D004797:Enzyme-Linked Immunosorbent Assay; D005353:Fibronectins / Q000378:metabolism*; D015686:Gene Products, env / Q000378:metabolism*; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D019302:HIV Envelope Protein gp160; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D066298:In Vitro Techniques; D011498:Protein Precursors / Q000378:metabolism*; D011994:Recombinant Proteins; D012463:Saliva / Q000378:metabolism*
D003172:Complement C1; D003181:Complement C4; D005353:Fibronectins; D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D007074:Immunoglobulin G; D011498:Protein Precursors; D011994:Recombinant Proteins; D015922:Complement C1q