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Epstein-Barr Virus gp350 Can Functionally Replace the Rhesus Lymphocryptovirus Major Membrane Glycoprotein and Does
Marissa Herrman1, Janine Mühe1, Carol Quink1
1Department of Medicine, Brigham and Women's Hospital, and Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
Journal of Virology
|November 13, 2015
Summary
Epstein-Barr virus (EBV) gp350 can replace rhesus lymphocryptovirus (rhLCV) gp350, enabling EBV vaccine research in macaques. This breakthrough allows direct testing of neutralizing antibodies against EBV infection in a relevant animal model.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Epstein-Barr virus (EBV) causes infectious mononucleosis and is linked to cancers.
- EBV vaccine development targets gp350, crucial for B cell neutralization.
- EBV infects both B cells and epithelial cells, necessitating models for oral mucosal infection.
Purpose of the Study:
- To determine if EBV's gp350 can functionally replace rhLCV's gp350.
- To establish a rhesus macaque model for EBV infection using a chimeric virus.
- To investigate EBV host range restriction and test neutralizing antibodies.
Main Methods:
- Constructed a chimeric rhLCV with EBV gp350 replacing native rhLCV gp350.
- Tested neutralization of the chimeric virus by an EBV-specific monoclonal antibody (MAb).
- Inoculated rhesus macaques orally with the chimeric virus to assess infection.
Main Results:
- The chimeric rhLCV efficiently immortalized macaque B cells in vitro.
- The chimeric virus established acute and persistent infection in rhesus macaques after oral inoculation.
- EBV gp350 functionally replaced rhLCV gp350 and conferred susceptibility to EBV-neutralizing MAbs.
Conclusions:
- Viral attachment via gp350 is not the mechanism for EBV's host range restriction in macaques.
- The humanized rhLCV model allows direct testing of EBV-specific neutralizing antibodies in vivo.
- This enhanced rhesus macaque model is crucial for developing effective EBV vaccines and understanding infection.
