AEGiS-11IAC: Role of factor H in resistance of HIV against complement-mediated destruction.

11th International AIDS Conference


Vancouver, British Columbia — July 7-12, 1996

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Role of factor H in resistance of HIV against complement-mediated destruction.

Int Conf AIDS 1996 Jul 7-12; 11:9 (abstract no. Mo.A.272)
Stoiber H, Pinter C, Spruth M, Mullauer B, Clivio A, Manfred P; Dierich Institut fur Hygiene, Universitat Innsbruck, Insbruck, Austria.

OBJECTIVE: In the study, presented here, the binding site of complement factor H (CFH) to the HIV envelope was mapped and a new functional CFH polymorphism was analyzed

METHODS: The binding of CFH-derived peptides, covering the whole short consensus repeat (SCR) 13, to gp120 and gp41 was determined by ELISA and inhibition assays in fluid phase. Interaction of CFH with the HIV envelope proteins was investigated by Scachard blot analysis and by FACS with HIV-1 infected cells

RESULTS: We identified two regions in the SCR 13 of CFH to mediate this interaction. The first region is located at amino acids (aa) 747-767, the second at aa 773-777. Peptides representing both regions inhibited the binding of CFH to gp120 and gp41 in ELISA. Moreover, these peptides bound directly to HIV. Using 125I-labeled CFH and HIV-infected cells, we calculated a kd of 10-8. In addition we found that various polymorphic forms of CFH show differences in binding to the envelope proteins of HIV-1 in ELISA and by FACS analysis.

CONCLUSIONS: The interaction of CFH with the envelope of HIV, which protects the virus against complement-mediated destruction, might probably be disturbed by CFH-derived peptides overlapping with the CFH binding site on SCR 13. To overcome this CFH-mediated resistance against lysis by human complement might provide a new strategy for vaccine development. Acknowledgment: The work was supported by the L. Boltzmann-Gesellschaft and the Land of Tyrol, by Grant N. 6204-009 of the V, VI and VII National AIDS Projects, Ministero della Sanita, Instituto Finalizzato Chimica Fine II, Consiglio Nazionale delle Ricerche (to A.C.).

Keywords: AEGIS, Complement Factor H, Complement, HIV-1, Acquired Immunodeficiency Syndrome, Binding Sites, Peptides, Anti-HIV Agents, Enzyme-Linked Immunosorbent Assay, Complement Activation, Human, immunology, ICA11KWDaegis,complementfactorh,complement,hiv-1,acquiredimmunodeficiencysyndrome,bindingsites,peptides,anti-hivagents,enzyme-linkedimmunosorbentassay,complementactivation,human,immunology,ica11

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MoA272

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