Extensive viral mimicry of 22 AIDS-related autoantigens by HIV-1 proteins and pathway analysis of 561 viral/human homologues suggest an initial treatable autoimmune component of AIDS


C.J. Carter, PolygenicPathways, Flat 4, 20 Upper Maze Hill, St Leonard's on Sea, East Sussex, TN38 OLG, UK. Tel.: +44 (0)1424 422201; e-mail: chris_car@yahoo.com


HIV-1 viral proteins, particularly the env protein, are homologous to 22 AIDS autoantigens, suggesting their creation by antiviral antibodies subsequently targeting human homologues. They include antibodies to T-cell receptors, CD4 and CD95, complement components, IgG, TNF and other immune-related proteins. Autoantibodies may compromise the immune system via knockdown of these key proteins, and autoimmune attack on the immune system itself, as supported by immune activation in early stages of infection and during the transition to AIDS. Over 500 human proteins contain pentapeptides or longer consensi, identical to viral peptides. Such homology explains the extensive viral/human interactome, likely related to the ability of viral homologues to compete with human counterparts as binding partners. Pathway analysis of these homologous proteins revealed their involvement in immune-related networks (e.g. natural killer cell toxicity/toll, T-cell/B-cell receptor signalling/antigen processing) and viral and bacterial entry and defence pathways (phagosome/lysosome pathways, DNA sensing/NOD/RIG-1 pathways) relevant to AIDS pathogenesis. At its inception, AIDS may have an autoimmune component selectively targeting the immune system. Immunosuppressive therapy or antibody removal, which has already achieved some success, might be therapeutically beneficial, particularly if targeted at removal of the culpable antibodies, via affinity dialysis.