Modeling adenovirus latency in human lymphocyte cell lines

Area of Science:

• Virology
• Immunology
• Cell Biology

Background:

• Species C adenovirus establishes latent infections in human tonsil and adenoid lymphocytes.
• Understanding adenovirus persistence in lymphocytes is crucial for managing chronic infections.

Purpose of the Study:

• To investigate the mechanisms by which adenovirus maintains a persistent infection in human lymphocytic cell lines.
• To elucidate the role of the coxsackie and adenovirus receptor (CAR) in viral persistence and reinfection.

Main Methods:

• Infection of four human lymphocytic cell lines (Jurkat, BJAB, Ramos, KE37) with Species C adenovirus.
• Monitoring of viral genome replication, cell proliferation, and CAR expression over time.
• Analysis of CAR downregulation using flow cytometry and assessment of reinfection after CAR reintroduction.

Main Results:

• BJAB, Ramos, and KE37 cells supported viral replication while maintaining proliferation.
• Persistently infected cells exhibited a two-stage downregulation of CAR expression, essential for viral genome maintenance.
• BJAB cells lost viral DNA, but CAR expression remained low, preventing adenovirus reinfection even after CAR reintroduction.

Conclusions:

• Species C adenovirus employs CAR downregulation as a key mechanism for establishing persistent infections in lymphocytes.
• Stable alterations in cellular gene expression following infection contribute to long-term viral persistence and resistance to reinfection.