Quantification of the CD55 and CD59, membrane inhibitors of complement on HIV-1 particles as a function of complement-mediated virolysis.
Previous studies have demonstrated that the murine monoclonal antibody (MoAb) NM-01 activates the human complement classical pathway resulting in lysis of human immunodeficiency virus (HIV). The present study was performed to determine the availability of the V3-loop of gp120 relative to the complement regulatory proteins, CD55 (DAF) and CD59 (HRF20) molecules on HIV. The results demonstrate that CD55 and CD59 exist on HIV virions, along with gp120 molecules. These findings suggest that activation of human complement on free viral particles is induced by MoAb NM-01 and that this occurs regardless of the presence of CD55 and CD59 molecules. The destruction of viral particles was demonstrated by a decrease in infectivity. The involvement of human complement in this process was confirmed with an immunoelectron microscopy technique by the presence of a human C9 to prove membrane attack complex (MAC). The results indicate that NM-01 can induce complement activation because of the ratios of CD55 and CD59 to gp120 molecules on HIV virions. The availability of the gp120 V3 domain on the virion is sufficient for binding of NM-01 and thereby the formation of MAC that results in virolysis.
Department of Microbiology, Jikei University School of Medicine, Tokyo, Japan.
M
M
Nakamura
H
H
Okada
H
H
Sasaki
K
K
Yoshida
M
M
Kamada
N
N
Okada
M
M
Terada
T
T
Ohno
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000914:Antibodies, Viral / Q000494:pharmacology*; D018958:CD55 Antigens / Q000032:analysis*; D018957:CD59 Antigens / Q000032:analysis*; D003167:Complement Activation; D015699:HIV Envelope Protein gp120 / Q000032:analysis*; D015497:HIV-1 / Q000737:chemistry / Q000187:drug effects / Q000276:immunology* / Q000648:ultrastructure; D006801:Humans; D016253:Microscopy, Immunoelectron; D014776:Virus Cultivation
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D018958:CD55 Antigens; D018957:CD59 Antigens; D015699:HIV Envelope Protein gp120