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Effect of CD4 gene expression on adenovirus replication
1Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
Journal of Virology
|November 1, 1994
Summary
Introducing the CD4 receptor gene into cells reduced adenovirus replication by hindering viral DNA nuclear entry. This finding impacts understanding of viral infection mechanisms and potential therapeutic targets for adenovirus and HIV.
Area of Science:
- Molecular Biology
- Virology
- Cell Biology
Background:
- The CD4 receptor is crucial for human immunodeficiency virus type 1 (HIV-1) entry into host cells.
- Adenovirus infection dynamics in cells expressing CD4 are not fully understood.
Purpose of the Study:
- To investigate the effect of CD4 receptor expression on adenovirus replication in human cell lines.
- To elucidate the specific stages of the adenovirus life cycle affected by CD4 presence.
Main Methods:
- Generation of CD4-expressing cell lines (KBT4 from KB cells, HeLaT4 from HeLa cells).
- Infection of parental and CD4-expressing cell lines with adenovirus type 5 (Ad5) and type 7 (Ad7).
- Analysis of viral adsorption, DNA uncoating, nuclear transport, RNA synthesis, and infectious virus yield.
Main Results:
- Adenovirus replication was significantly reduced in CD4-expressing cells (KBT4, HeLaT4) compared to parental cells.
- Viral adsorption and DNA uncoating were unaffected by CD4 expression.
- Nuclear migration and early RNA synthesis of viral DNA were delayed and reduced in CD4-expressing cells, particularly for Ad7.
- Infectious virus yields were similar when infections were initiated by naked viral DNA transfection.
Conclusions:
- CD4 receptor expression interferes with post-uncoating steps of adenovirus infection, specifically the transport of viral DNA to the nucleus.
- This interference is independent of viral adsorption and DNA uncoating.
- The findings suggest a potential role for CD4 in regulating intracellular viral trafficking, offering insights into adenovirus pathogenesis and host-pathogen interactions.