scholarly journals Novel anti-CD4 monoclonal antibodies separate human immunodeficiency virus infection and fusion of CD4+ cells from virus binding.

1990 ◽  
Vol 172 (4) ◽  
pp. 1233-1242 ◽  
Author(s):  
D Healey ◽  
L Dianda ◽  
J P Moore ◽  
J S McDougal ◽  
M J Moore ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Monoclonal Antibodies ◽  
Membrane Fusion ◽  
Syncytium Formation ◽  
Active Role ◽  
Virus Infectivity ◽  
Virus Binding ◽  
Virus Envelope ◽  
Immunodeficiency Virus ◽  
Glycoprotein Gp120

Human immunodeficiency virus (HIV) binds to cells via an interaction between CD4 and the virus envelope glycoprotein, gp120. Previous studies have localized the high affinity binding site for gp120 to the first domain of CD4, and monoclonal antibodies (mAbs) reactive with this region compete with gp120 binding and thereby block virus infectivity and syncytium formation. Despite a detailed understanding of the binding of gp120 to CD4, little is known of subsequent events leading to membrane fusion and virus entry. We describe two new mAbs reactive with the third domain of CD4 that inhibit steps subsequent to virus binding critical for HIV infectivity and cell fusion. Binding of recombinant gp120 or virus to CD4 is not inhibited by these antibodies, whereas infection and syncytium formation by a number of HIV isolates are blocked. These findings demonstrate that in addition to virus binding, CD4 may have an active role in membrane fusion.

scholarly journals Importance of Membrane Fusion Mediated by Human Immunodeficiency Virus Envelope Glycoproteins for Lysis of Primary CD4-Positive T Cells

2000 ◽  
Vol 74 (22) ◽  
pp. 10690-10698 ◽  
Author(s):  
Jason A. LaBonte ◽  
Trushar Patel ◽  
Wolfgang Hofmann ◽  
Joseph Sodroski
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
Membrane Fusion ◽  
Single Cells ◽  
Syncytium Formation ◽  
Envelope Glycoproteins ◽  
Virus Envelope ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT In established T-cell lines, the membrane-fusing capacity of the human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins mediates cytopathic effects, both syncytium formation and single-cell lysis. Furthermore, changes in the HIV-1 envelope glycoproteins are responsible for the increased CD4+ T-cell-depleting ability observed in infected monkeys upon in vivo passage of simian-human immunodeficiency virus (SHIV) chimeras. In this study, a panel of SHIV envelope glycoproteins and their mutant counterparts defective in membrane-fusing capacity were expressed in primary human CD4+ T cells. Compared with controls, all of the functional HIV-1 envelope glycoproteins induced cell death in primary CD4+ T-cell cultures, whereas the membrane fusion-defective mutants did not. Death occurred almost exclusively in envelope glycoprotein-expressing cells and not in bystander cells. Under standard culture conditions, most dying cells underwent lysis as single cells. When the cells were cultured at high density to promote syncytium formation, the envelope glycoproteins of the passaged, pathogenic SHIVs induced more syncytia than those of the respective parental SHIV. These results demonstrate that the HIV-1 envelope glycoproteins induce the death of primary CD4+ T lymphocytes by membrane fusion-dependent processes.

scholarly journals Antibody raised against soluble CD4-rgp120 complex recognizes the CD4 moiety and blocks membrane fusion without inhibiting CD4-gp120 binding.

1990 ◽  
Vol 172 (4) ◽  
pp. 1143-1150 ◽  
Author(s):  
F Celada ◽  
C Cambiaggi ◽  
J Maccari ◽  
S Burastero ◽  
T Gregory ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Monoclonal Antibodies ◽  
Cell Surface ◽  
Membrane Fusion ◽  
Humoral Response ◽  
Gp120 Binding ◽  
Binding Event ◽  
Immunodeficiency Virus ◽  
Syncytia Formation ◽  
Soluble Cd4

We studied the humoral response of mice immunized with soluble CD4-rgp120 complex, testing polyclonal and monoclonal antibodies (mAbs) with the aim of identifying molecular changes that take place after the first interaction between human immunodeficiency virus and the cell surface. The antisera had a paradoxically high syncytia-blocking titer associated with anti-CD4 specificity, while their capacity to inhibit CD4-gp120 binding was relatively modest. One of the mAbs produced from these responders blocks syncytia formation but does not inhibit CD4 interaction with gp120. Apparently, this mAb interacts with the CD4 moiety of CD4-gp120 complex and prevents a post-binding event necessary for membrane fusion and viral infection.

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