Complement decay-accelerating factor, also known asCD55 orDAF, is aprotein that, in humans, is encoded by theCD55gene.[5]
DAF regulates thecomplement system on thecell surface. It recognizes C4b and C3b fragments that are created during activation of C4 (classical orlectin pathway) or C3 (alternative pathway). Interaction of DAF with cell-associated C4b of the classical and lectin pathways interferes with the conversion of C2 to C2b, thereby preventing formation of the C4b2aC3-convertase, and interaction of DAF with C3b of the alternative pathway interferes with the conversion of factor B to Bb by factor D, thereby preventing formation of the C3bBb C3 convertase of the alternative pathway. Thus, by limiting the amplification convertases of the complementcascade, DAF indirectly blocks the formation of themembrane attack complex.[6]
Thisglycoprotein is broadly distributed amonghematopoietic and non-hematopoietic cells. It is a determinant for the Cromer blood group system.
DAF contains fourcomplement control protein (CCP) repeats with a single N-linked glycan positioned between CCP1 and CCP2. CCP2, CCP3, CCP4 and three consecutivelysine residues in a positively charged pocket between CCP2 and CCP3 are involved in its inhibition of thealternate complement pathway. CCP2 and CCP3 alone are involved in its inhibition of theclassical pathway.[7]
Because DAF is aGPI-anchored protein, its expression is reduced in persons with mutations that reduce GPI levels such as those withparoxysmal nocturnal hemoglobinuria (PNH). In PNH disorder,red blood cells with very low levels of DAF andCD59 undergocomplement-mediated hemolysis. Symptoms include low red blood cell count (anemia), fatigue, and episodes of dark colored urine and other complications.[8]
DAF is used as a receptor by somecoxsackieviruses and otherenteroviruses.[9] Recombinant soluble DAF-Fc has been tested in mice as an anti-enterovirus therapy for heart damage;[10] however, the human enterovirus that was tested binds much more strongly to human DAF than tomouse orrat DAF. Echoviruses and coxsackie B viruses that use human decay-accelerating factor (DAF) as a receptor do not bind the rodent analogues of DAF.[11] and DAF-Fc has yet to be tested in humans.
Binding of DAF to human HIV-1 when the virons are budding from the surface of infected cells protects HIV-1 from complement mediated lysis.[12][13]
Selinka HC, Wolde A, Sauter M, et al. (2004). "Virus-receptor interactions of coxsackie B viruses and their putative influence on cardiotropism".Med. Microbiol. Immunol.193 (2–3):127–31.doi:10.1007/s00430-003-0193-y.PMID12920584.S2CID21083098.
