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Is there a unique episome in EBV transformed B cells?
L D Klaman1, E A Hurley, D A Thorley-Lawson
1Department of Pathology, Tufts University School of Medicine, Boston, Massachusetts 02111.
Virology
|December 1, 1991
Summary
Epstein-Barr virus infection in B cells leads to an average of 0.65 episomal genomes per cell. Most B cell clones arise from a single episome formation, suggesting a selection mechanism for single circular genomes.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Epstein-Barr virus (EBV) is a human herpesvirus known to establish latent infections in B lymphocytes.
- Episome formation, the generation of circular DNA molecules, is a key event in EBV latency.
- Understanding the dynamics of episome formation is crucial for comprehending EBV-driven B cell transformation.
Purpose of the Study:
- To quantify the frequency of Epstein-Barr virus episome formation in resting B cells.
- To investigate the distribution of episomal genomes within B cell clones post-infection.
- To identify potential mechanisms regulating episome establishment during early EBV infection.
Main Methods:
- Infection of resting human B cells with Epstein-Barr virus.
- Quantification of episomal genomes per cell using quantitative molecular assays.
- Analysis of B cell clone origins to determine the number of circularization events.
Main Results:
- An average of 0.65 Epstein-Barr virus episomal genomes were detected per B cell 36 hours post-infection.
- Analysis of B cell clones revealed that 32 out of 33 originated from a single episome formation event.
- This observed distribution significantly deviates from predicted random circularization patterns.
Conclusions:
- A strong selection or exclusion mechanism appears to operate early in Epstein-Barr virus infection.
- This mechanism favors the formation or stable retention of a single episomal genome per B cell.
- The findings provide insights into the regulation of viral genome copy number during the establishment of latency.