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Isolation and Quantification of Epstein-Barr Virus from the P3HR1 Cell Line
Published on: September 28, 2022
Epstein-Barr virus-encoded dUTPase modulates immune function and induces sickness behavior in mice
David A Padgett1, Andrew K Hotchkiss, Leah M Pyter
1Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University Medical Center, Columbus, Ohio, USA.
Abstract:
Epstein-Barr virus (EBV) is the causative agent of infectious mononucleosis (IM). In addition, latent infections with EBV are associated with nasopharyngeal carcinoma (NPC) and Burkitt's Lymphoma (BL). Antibodies to several EBV-encoded early antigens (EA) are often observed in patients with NPC and BL, however, the role of EBV-encoded proteins in the etiology of these and other EBV-associated diseases is not completely understood. The EA complex encodes for at least six different viral enzymes including deoxyuridine triphosphate nucleotidohydrolase (dUTPase). dUTPase has recently been shown to modulate activation of human peripheral blood mononuclear cells in vitro (unpublished data). Therefore, these studies were designed to test whether dUTPase would modulate immune function in an in vivo model. Mice were injected with purified EBV dUTPase, and baseline immune function and sickness behaviors were measured. EBV dUTPase treatment inhibited replication of mitogen-stimulated lymphocytes obtained from treated mice. These lymphocytes were also less able to synthesize interferon-gamma after re-stimulation. In addition, treatment with dUTPase induced sickness behaviors. For example, as compared to control animals, dUTPase-treated animals lost body mass, had elevated body temperature, and displayed diminished locomotor activity. These data suggest that individual viral proteins may play a role in the pathophysiology of EBV associated disease.
Insights
Epstein-Barr virus deoxyuridine triphosphate nucleotidohydrolase (dUTPase) inhibits lymphocyte replication and interferon-gamma synthesis in mice. EBV dUTPase also induced sickness behaviors, suggesting viral proteins contribute to EBV-associated diseases.
Area of Science:
- Virology
- Immunology
- Molecular Biology
Background:
- Epstein-Barr virus (EBV) causes infectious mononucleosis and is linked to nasopharyngeal carcinoma and Burkitt's Lymphoma.
- Antibodies to EBV early antigens (EA) are common in NPC and BL patients, but the role of EBV proteins in disease etiology is unclear.
- The EBV EA complex includes deoxyuridine triphosphate nucleotidohydrolase (dUTPase), which may modulate immune cell activation.
Purpose of the Study:
- To investigate the in vivo effects of EBV-encoded dUTPase on immune function and sickness behaviors.
- To determine if EBV dUTPase influences lymphocyte replication and cytokine production.
- To assess the impact of EBV dUTPase administration on animal physiology and behavior.
Main Methods:
- Mice were injected with purified EBV dUTPase.
- Immune function, including mitogen-stimulated lymphocyte replication and interferon-gamma synthesis, was measured.
- Sickness behaviors such as body mass, body temperature, and locomotor activity were assessed.
Main Results:
- EBV dUTPase treatment inhibited the replication of mitogen-stimulated lymphocytes from treated mice.
- Lymphocytes from dUTPase-treated mice showed reduced interferon-gamma synthesis upon re-stimulation.
- Dutpase-treated mice exhibited sickness behaviors, including weight loss, elevated body temperature, and decreased activity.
Conclusions:
- EBV dUTPase modulates immune function in vivo by inhibiting lymphocyte proliferation and cytokine production.
- EBV dUTPase induces sickness behaviors, indicating a direct role in viral pathophysiology.
- Individual viral proteins, such as EBV dUTPase, may contribute to the development of EBV-associated diseases.
