HIV GLYCOPROTEIN-41 AND COMPLEMENT FACTOR-H INTERACT WITH EACH OTHER AND SHARE FUNCTIONAL AS WELL AS ANTIGENIC HOMOLOGY

We have shown that complement factor H (CFH) interacts with HIV-1 at t he level of the sequence Env 105-119, contained in the C1 domain of gp 120. CFH interaction with HIV was evident only after dissociation of t he Env complex induced by exposure to sCD4, We hypothesized that CFH c ould act as a gp41 analog in the interaction with Env 105-119. A panel of partially overlapping, synthetic peptides reproducing the extracel lular portion of gp41 was therefore used to compete the binding of CFH to Env 105-119. Three sets of peptides that competed this interaction were identified. These peptides defined a region of functional homolo gy between the gp41 molecule and CFH (Env 580-600), and two regions of interaction (Env 620-640 and Env 650-670), In addition to this, a mon oclonal antibody directed against peptide Env 580-600 and a polyclonal mouse antiserum raised against recombinant gp41 were shown to recogni ze CFH in Western blots and ELISA, respectively, also defining a regio n of antigenic homology between gp41 and CFH. These data provide evide nce for interaction and molecular mimicry between an HIV structural pr otein and a negative regulator of the complement pathway. We show here that CFH can interact with both HIV Env proteins, suggesting a possib le and efficient mechanism of downregulation of the complement cascade at the surface of infected cells.