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 the level of the sequence Env 105-119, contained in the C1 domain of gp120. CFH interaction with HIV was evident only after dissociation of the Env complex induced by exposure to sCD4. We hypothesized that CFH could act as a gp41 analog in the interaction with Env 105-119. A panel of partially overlapping, synthetic peptides reproducing the extracellular 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 homology 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 monoclonal antibody directed against peptide Env 580-600 and a polyclonal mouse antiserum raised against recombinant gp41 were shown to recognize CFH in Western blots and ELISA, respectively, also defining a region of antigenic homology between gp41 and CFH. These data provide evidence for interaction and molecular mimicry between an HIV structural protein and a negative regulator of the complement pathway. We show here that CFH can interact with both HIV Env proteins, suggesting a possible and efficient mechanism of downregulation of the complement cascade at the surface of infected cells.