       Document 0684
 DOCN  M9640684
 TI    Efficient destruction of human immunodeficiency virus in human serum by
       inhibiting the protective action of complement factor H and decay
       accelerating factor (DAF, CD55).
 DT    9604
 AU    Stoiber H; Pinter C; Siccardi AG; Clivio A; Dierich MP; Institut fur
       Hygiene, Ludwig Boltzmann Institut fur AIDS; Forschung, Innsbruck,
       Austria.
 SO    J Exp Med. 1996 Jan 1;183(1):307-10. Unique Identifier : AIDSLINE
       MED/96136775
 AB    Activation of the human complement system leads to complement deposition
       on human immunodeficiency virus (HIV) and HIV-infected cells without
       causing efficient complement-mediated lysis. Even in the presence of
       HIV-specific antibodies, only a few particles are destroyed,
       demonstrating that HIV is intrinsically resistant to human complement.
       Here we report that, in addition to decay accelerating factor (DAF)
       being partially responsible, human complement factor H (CFH), a humoral
       negative regulator of complement activation, is most critical for this
       resistance. In the presence of HIV-specific antibodies, sera devoid of
       CFH (total genetic deficiency or normal human serum depleted of CFH by
       affinity chromatography) lysed free virus and HIV-infected but not
       uninfected cells. In the presence of CFH, lysis of HIV was only obtained
       when binding of CFH to gp41 was inhibited by a monoclonal antibody
       against a main CFH-binding site in gp41. Since CFH is an abundant
       protein in serum, and high local concentration of CFH can be obtained at
       the surface of HIV as the result of specific interactions of CFH with
       the HIV envelope, it is proposed that the resistance of HIV and
       HIV-infected cells against complement-mediated lysis in vivo is
       dependent on DAF and CFH and can be overcome by suppressing this
       protection. Neutralization of HIV may be achieved by antibodies against
       DAF and, more importantly, antibodies against CFH-binding sites on HIV
       envelope proteins.
 DE    Acquired Immunodeficiency Syndrome/BLOOD/IMMUNOLOGY  Antigens,
       CD55/*PHARMACOLOGY  Blood/*IMMUNOLOGY  *Complement Activation
       Complement Factor H/*PHARMACOLOGY  Human  HIV Antibodies  HIV Envelope
       Protein gp41/IMMUNOLOGY  HIV-1/*DRUG EFFECTS  Support, Non-U.S. Gov't
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

