Human monoclonal antibodies to the human immunodeficiency virus type 1 (HIV-1) transmembrane glycoprotein gp41 enhance HIV-1 infection in vitro.
Three of 16 human monoclonal antibodies (hu-mAbs) enhanced human immunodeficiency virus type 1 (HIV-1) infection of MT-2 target cells by means of a mechanism that is dependent on complement. Enhanced infections are characterized by an increase in cytopathic effects and antigen synthesis as well as an increase in the production of progeny virus as detected by release of reverse transcriptase activity and infectious virus into the culture medium. Analyses by radioimmunoprecipitation, Western blot, and ELISA using the pENV9 envelope fragment localize the antigenic specificities of these three hu-mAbs to the N-terminal two-thirds of the transmembrane protein gp41. Competitive binding experiments indicate that the hu-mAbs are reactive with immunodominant epitopes of gp41 recognized by sera from essentially all HIV-1-infected subjects. Combination dose-effect experiments demonstrate that these hu-mAbs can act synergistically in vitro to enhance HIV-1 infection. These data demonstrate that hu-mAbs directed against the HIV-1 transmembrane glycoprotein gp41 can enhance HIV-1 infection in vitro. The availability of these reagents allows for the mapping of enhancing epitopes on HIV-1 and provides a means for studying whether deletion of such enhancing epitopes from candidate HIV-1 vaccines might improve the protective immune response to HIV-1 in immunized humans and chimpanzees.
Robinson
W E
WE
Department of Pathology, Vanderbilt University, Nashville, TN 37232.
Kawamura
T
T
Gorny
M K
MK
Lake
D
D
Xu
J Y
JY
Matsumoto
Y
Y
Sugano
T
T
Masuho
Y
Y
Mitchell
W M
WM
Hersh
E
E
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D000936:Antigen-Antibody Complex; D001710:Biotin; D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D015483:HIV Antibodies / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D009500:Neutralization Tests; D014774:Virulence
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D001710:Biotin