Complement-dependent virolysis of HIV-1 with monoclonal antibody NM-01.
Previous studies have described the isolation of monoclonal antibodies that neutralize human immunodeficiency virus type 1 (HIV-1). However, although certain antibodies are capable of blocking infection of CD4+ cells, the antibody-HIV-1 complex could potentially remain infectious and enter cells by an Fc receptor-mediated mechanism. Indeed, one goal of HIV-1 therapy with antibodies is the development of reagents capable of killing virus. The present studies with murine monoclonal antibody (MoAb) NM-01 demonstrate complement-mediated lysis of HIV-1. NM-01-dependent virolysis has been visualized by electron microscopy. Virus particles treated with NM-01 and rabbit or human complement undergo a process of outer envelope rupture and loss of the electron-dense core. The involvement of human complement in this process was confirmed by the presence of C9 in association with MoAb NM-01 immune complexes. In contrast, virolysis was not detectable with antibody or complement alone. Moreover, although MoAb NM-01 alone is capable of neutralizing HIV-1, the presence of rabbit complement was associated with over a 10-fold decrease in infectivity. Similar but less pronounced effects were observed with human complement. These findings support a potential role for antibody-dependent complement-mediated virolysis in HIV-1 therapy.
Nakamura
M
M
Department of Microbiology, Jikei University School of Medicine, Tokyo, Japan.
Sasaki
H
H
Terada
M
M
Ohno
T
T
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002460:Cell Line; D003165:Complement System Proteins / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology / Q000648:ultrastructure; D006801:Humans; D051379:Mice; D008854:Microscopy, Electron; D016253:Microscopy, Immunoelectron; D008969:Molecular Sequence Data; D014779:Virus Replication
D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D003165:Complement System Proteins