Persistent productive HIV infection in EBV-transformed B lymphocytes

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• B-cells are crucial components of the adaptive immune system.
• Human immunodeficiency virus (HIV) primarily targets CD4-positive T-cells.
• The role of B-cells in HIV infection dynamics requires further elucidation.

Purpose of the Study:

• To investigate the susceptibility of Epstein-Barr virus (EBV)-transformed B-cell lines to HIV infection.
• To characterize the productive HIV infection in B-cells and its dependence on CD4 molecules.
• To determine if B-cells can serve as a chronic reservoir for infectious HIV.

Main Methods:

• Establishment of 14 B-cell lines from HIV-seronegative and seropositive individuals.
• Infection of B-cell lines with the HIV SF-2 strain.
• Assessment of CD4 receptor expression using flow cytometry.
• Blocking of HIV infection using anti-CD4 monoclonal antibodies.
• Monitoring of viral antigen (p24) production and infectious virus release over 8 months.

Main Results:

• All B-cell lines, regardless of CD4 expression levels, were susceptible to HIV infection.
• HIV infection was blocked by antibodies targeting the CD4 molecule's attachment site.
• B-cell lines with higher CD4 expression showed more rapid and higher p24 antigen production.
• Infected B-cells supported chronic HIV replication and produced infectious virus for over 8 months.
• HIV-infected B-cells produced more viral antigens than infected T-cell lines (HUT-78).

Conclusions:

• Transformed B-cells can be chronically and productively infected by HIV through CD4 molecule interaction.
• B-cells may represent a significant source of infectious HIV in infected individuals.
• These findings highlight the potential role of B-cells in HIV persistence and transmission.