EBV persistence without its EBNA3A and 3C oncogenes in vivo

Area of Science:

• Virology
• Immunology
• Oncology

Background:

• Epstein Barr virus (EBV) infects most humans, establishing lifelong latent infections.
• EBV oncoproteins EBNA3A and EBNA3C are crucial for B cell transformation and are found in lymphomas.
• The necessity of EBNA3A and EBNA3C for persistent EBV infection in vivo remains unclear.

Purpose of the Study:

• To investigate the role of EBNA3A and EBNA3C in maintaining persistent EBV infection in vivo.
• To determine if EBV can establish latent infection without EBNA3A or EBNA3C expression.

Main Methods:

• Infection of humanized NOD-scid γcnull (huNSG) mice with EBV mutants lacking EBNA3A or EBNA3C.
• Monitoring of viral persistence, tumor formation, and gene expression in infected mice.
• In vitro studies assessing B cell survival with CD40 stimulation.

Main Results:

• EBV mutants lacking EBNA3A or EBNA3C established latent infections in huNSG mice for at least 3 months without causing tumors.
• Viral persistence in the absence of EBNA3A/EBNA3C was supported by B cell proliferation and early latent gene expression.
• EBV-infected B cells deficient in EBNA3A/EBNA3C showed increased survival upon CD40 stimulation in vitro.

Conclusions:

• EBNA3A and EBNA3C are not essential for the establishment or maintenance of chronic EBV latent infection in vivo.
• EBV can adopt a persistence strategy resembling healthy carriers even without its oncogenic proteins.
• CD40 signaling may compensate for the absence of EBNA3A/EBNA3C in supporting viral persistence.