B cells malignantly transformed by human immunodeficiency virus are polyclonal

Area of Science:

• Virology and Immunology
• Cancer Research
• Genetics

Background:

• The precise roles of human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV) in acquired immune deficiency syndrome (AIDS)-related lymphomas remain unclear.
• A novel human B cell line, B-HIV, containing both EBV and HIV genomes, has been developed to model AIDS-related lymphomagenesis and exhibits malignant transformation.

Purpose of the Study:

• To determine the number of independent transformation events occurring during HIV infection in the B-HIV cell line.
• To elucidate the polyclonal nature of the B-HIV cell line and the integration patterns of HIV sequences.

Main Methods:

• Development of a B-HIV cell line by exposing Epstein-Barr virus (EBV)-seropositive donor B cells to HIV.
• Utilizing fluorescence in situ hybridization (FISH) to analyze the integration sites of HIV genomes within the B-HIV cell line.
• Comparative analysis with a clonal HIV-infected human T cell line (8E5) as a control.

Main Results:

• The B-HIV cell line demonstrated multiple, distinct sites of HIV integration, with greater than or equal to 25 integration events identified.
• In contrast, the control 8E5 T cell line showed HIV sequences integrated at a single, specific chromosomal location (band q22 in chromosome 13).
• These findings indicate that the B-HIV cell line is polyclonal.

Conclusions:

• The B-HIV cell line is polyclonal, reflecting multiple independent transformation events.
• HIV sequences are integrated at numerous variable chromosomal sites across different cells within the B-HIV line.
• This polyclonal nature and variable integration pattern provide insights into AIDS-related lymphomagenesis.