Complement-mediated, antibody-dependent enhancement of HIV-1 infection in vitro is characterized by increased protein and RNA syntheses and infectious virus release.
Antibody-dependent enhancement (ADE) of human immunodeficiency virus type 1 (HIV-1) infection in vitro has been described recently and was shown to occur by two mechanisms: either participation of the alternative pathway of complement or to involve an Fc receptor-mediated, complement-independent mechanism. Complement-mediated ADE results in an accelerated cytopathic effect in target cells that can abrogate the protective properties of neutralizing antibodies. This study characterizes the surface antigens of MT-2 cells using flow cytometric analysis and shows that these cells express high levels of both CD4 and complement receptor type 2 (CR2) while several CD4+ cell lines that do not demonstrate complement-mediated ADE lack high levels of complement receptors. Further, utilizing MT-2 cell cultures, it is demonstrated that complement-mediated ADE of HIV-1 infection is conferred by the sera from more than 80% of HIV-1 antibody-positive individuals (N = 85). Complement-mediated ADE of HIV-1 infection causes an acceleration of several parameters indicative of HIV-1 infection in vitro including increased HIV-1 antigen synthesis as detected by indirect immunofluorescence, RNA accumulation as measured by a solution hybridization protocol, reverse transcriptase release, and progeny virus production.
Robinson
W E
WE
Department of Pathology, Vanderbilt University, Nashville, Tennessee 37232.
Montefiori
D C
DC
Gillespie
D H
DH
Mitchell
W M
WM
D002460:Cell Line; D003588:Cytopathogenic Effect, Viral; D005434:Flow Cytometry; D015483:HIV Antibodies / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology; D015497:HIV-1 / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D015347:RNA Probes; D012367:RNA, Viral / Q000096:biosynthesis*; D012194:RNA-Directed DNA Polymerase / Q000096:biosynthesis; D011951:Receptors, Complement / Q000032:analysis / Q000502:physiology*; D014779:Virus Replication
D015483:HIV Antibodies; D015488:HIV Antigens; D015347:RNA Probes; D012367:RNA, Viral; D011951:Receptors, Complement; D012194:RNA-Directed DNA Polymerase