Regulation of human immunodeficiency virus gp160-mediated cell fusion by antibodies against fusion regulatory protein 1.
We have isolated new MAbs directed against the human fusion regulatory protein 1 (FRP-1; CD98) molecule using human FRP-1-expressing L929 cells as antigens. The biological activities, and in particular the human immunodeficiency virus (HIV)-mediated fusion regulatory activity of seven anti-FRP-1/CD98 MAbs were analysed using the U937/gp160 cell line, which is a CD4+ U937 cell line expressing HIV gp160. Two MAbs induced multinucleated giant cell formation in U937/gp160 cells and the other five MAbs showed no fusion-inducing ability. However, four of these MAbs suppressed multinucleated giant cell formation of U937/gp160 cells induced by the activating anti-FRP-1 MAbs. Interestingly, five of the MAbs induced multinucleated giant cells in peripheral blood monocytes and one MAb showing fusion-inducing ability in U937/gp160 cells suppressed multinucleated giant cell formation of monocytes induced by anti-FRP-1 MAbs. Furthermore, four of the anti-FRP-1 MAbs suppressed cell fusion of Jurkat/gp160 cells, which are Jurkat cells expressing HIV gp160. Thus, FRP-1/CD98 is capable of either activating or inhibiting HIV-mediated cell fusion depending on whether an enhancing or inhibiting antibody is used, indicating that FRP-1/CD98 is a multipotential molecule. Thus, HIV-mediated cell fusion can be regulated by modification of the FRP-1 system. Furthermore, the present study demonstrates that the FRP-1 and FRP-2 systems are interdependent.
Ohgimoto
S
S
Department of Microbiology, Mie University School of Medicine, Japan.
Tabata
N
N
Suga
S
S
Tsurudome
M
M
Kawano
M
M
Nishio
M
M
Okamoto
K
K
Komada
H
H
Watanabe
N
N
Ito
Y
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D015703:Antigens, CD / Q000502:physiology*; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000502:physiology*; D002459:Cell Fusion; D005353:Fibronectins / Q000494:pharmacology; D027261:Fusion Regulatory Protein-1; D019302:HIV Envelope Protein gp160 / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D002352:Carrier Proteins; D005353:Fibronectins; D027261:Fusion Regulatory Protein-1; D019302:HIV Envelope Protein gp160