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Identification of CD7 glycoprotein as an accessory molecule in HIV-1-mediated syncytium formation and cellfree
A I Sato1, F B Balamuth, K E Ugen
1Department of Pathology, University of Pennsylvania, Philadelphia 19104.
Insights
The human T cell surface molecule CD7 plays a crucial role in Human Immunodeficiency Virus (HIV) infection. Blocking CD7 significantly inhibits HIV-induced cell fusion and viral spread, highlighting its importance in the infection process.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Human Immunodeficiency Virus (HIV) infection of CD4+ T cells involves cell-to-cell fusion, leading to syncytium formation.
- Membrane fusion is a critical step for both cell-free virion infection and syncytium development.
Purpose of the Study:
- To investigate the role of the human T cell surface molecule CD7 in the HIV-1 fusion process.
- To determine if CD7 is a target for inhibiting HIV-1 infection and cell fusion.
Main Methods:
- Utilized anti-CD7 monoclonal antibodies (mAbs) to block HIV-1-induced cell-cell fusion and cell-free infection in SupT1 cells.
- Performed epitope mapping to identify regions on CD7 involved in membrane fusion inhibition.
- Assessed infectability of CD7-deficient cells by cell-free virus and their susceptibility to fusion inhibition.
Main Results:
- Anti-CD7 mAbs effectively inhibited HIV-1-induced cell-cell fusion and prevented cell-free infection.
- The inhibitory effect of anti-CD7 antibodies was not due to cross-reactivity with CD4 or viral proteins.
- Cells lacking CD7 expression (CD7-) showed reduced susceptibility to cell-free viral infection and were more easily inhibited from fusing.
Conclusions:
- Human CD7 is a key molecule involved in the HIV-1 fusion process.
- Targeting CD7 presents a potential strategy for inhibiting HIV-1 infection and preventing syncytium formation.
Abstract:
A major cytopathic effect seen upon in vitro infection of CD4+ human T cells by the HIV is cell-to-cell fusion that results in giant cell (or syncytium) formation. Membrane fusion is required for infection by cellfree virions and in syncytium formation. We report here that the human T cell surface molecule, CD7, is important for the HIV-1 fusion process. CD7 is a roughly 40-kDa glycoprotein member of the Ig supergene family that is expressed early in the ontogeny of thymocytes and on the majority of peripheral blood T cells, as well as on NK cells and a small subpopulation of B cells. Anti-CD7 mAbs inhibited HIV-1-induced cell-cell fusion and prevented cellfree infection of SupT1 cells. The antisyncytial activity of the CD7 Abs is not because of cross-reactivity with CD4 or with viral proteins. Epitope mapping revealed at least two regions of the molecule that are important for preventing membrane fusion. Cells rendered CD7- are poorly infectable by cellfree virus. Additionally, cells rendered CD7- are more easily inhibited from fusing in syncytium formation assays. The collective results support a central role for human CD7 in the process of HIV infection.