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Cofactor requirement for human immunodeficiency virus type 1 entry into a CD4-expressing human cell line
1Department of Molecular Medicine, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104-2092.
Journal of Virology
|October 1, 1993
Summary
Human immunodeficiency virus type 1 (HIV-1) infection requires more than CD4 expression. Certain human cells resist HIV-1 entry, indicating additional cellular factors are necessary for infection.
Area of Science:
- Virology
- Cell Biology
- Immunology
Background:
- CD4 receptor expression is crucial but not always sufficient for HIV-1 infection.
- Many cell lines expressing CD4 remain resistant to HIV-1, suggesting additional cellular factors are involved.
Purpose of the Study:
- To investigate the cellular factors required for HIV-1 entry and infection.
- To identify the mechanism of resistance in CD4-expressing cells that do not support HIV-1 infection.
Main Methods:
- Generated a CD4-expressing glioblastoma cell line (U373-CD4) resistant to HIV-1.
- Created heterokaryons by fusing U373-CD4 cells with HeLa cells.
- Developed a hybrid clone from U373-CD4 and HeLa cells.
Main Results:
- U373-CD4 cells, despite CD4 expression, were resistant to HIV-1 infection at the entry stage.
- Fusion with HeLa cells enabled HIV-1 entry into U373-CD4 cells.
- A U373-CD4/HeLa hybrid clone supported efficient HIV-1 replication.
Conclusions:
- HeLa cells possess a factor(s) that complements the viral entry defect in U373-CD4 cells.
- Efficient CD4-mediated HIV-1 infection requires cellular factors beyond CD4 expression.
- These findings highlight the complexity of HIV-1 cellular tropism and entry mechanisms.
