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1996-03-04
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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).