Jes. Hansen et al., ENHANCEMENT OF RETROVIRAL INFECTION IN-VITRO BY ANTI-LE(Y) IGG - REVERSAL BY HUMANIZATION OF MONOCLONAL MOUSE ANTIBODY, APMIS. Acta pathologica, microbiologica et immunologica Scandinavica, 101(9), 1993, pp. 711-718
Monoclonal mouse IgG, antibody (ABL 364) against the carbohydrate Le(y
) antigen enhanced infection in vitro with HTLV-1 and with HIV-1 when
propagated in both transformed and normal lymphocytes. Enhancement was
independent of complement, occurred with both lymphocytes and monocyt
es as target cells, and did not use either Le(y) epitopes on target ce
lls for cross-linkage of virus to the cell or the Fc part of the antib
ody as a ligand for any cellular receptor. For enhancement to occur, b
inding of anti-Le(y) antibody to virus was required to take place befo
re virus binding to its specific receptor with no indication of any al
ternative pathway of infection, as evidenced by abrogation of enhancem
ent by anti-CD4 MAb or soluble recombinant CD4, and also the inability
of anti-Le(y) MAb to mediate HIV infection of HSB-2 cells in which HT
LV-1/HIV pseudovirus infection was enhanced. While F(ab)2 fragments of
ABL 364 also enhanced infection, a human/mouse chimeric antibody and
a fully humanized antibody had no enhancing effect on free virus infec
tion. We suggest that binding of anti-Le(y) ABL 364 or its F(ab), frag
ment induced a conformational change in the gp120 oligomers facilitati
ng the process of infection, and that this function was abrogated by t
he IgG1 Fc of the chimeric and the humanized antibodies. The observati
ons indicate that the non-paratope domains of antiviral antibodies can
influence their function as neutralizing or enhancing for infection.