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Epstein-Barr virus-infected marmoset cells do not form lymphomas in mice with severe combined immunodeficiency
1Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06510.
Abstract:
EBV has been associated with several malignancies in humans. EBV can also infect marmoset B lymphocytes, which, as opposed to human B cells, are permissive for lytic Epstein-Barr viral replication. Mice with a severe combined immunodeficiency phenotype (SCID mice) are extremely susceptible to EBV-induced lymphomagenesis when inoculated with EBV-infected lymphocytes. We inoculated SCID mice with human and marmoset lymphoblastoid cells infected with the same EBV isolates. The marmoset cells never gave rise to lymphomas, even after the administration of acyclovir or an anti-natural killer cell antibody and observation periods of up to 16 wk. In contrast, the human lymphoblastoid cells nearly always gave rise to lymphomas within 8 wk. Furthermore, human lymphoblastoid cells genetically engineered to permit lytic EBV replication also readily formed tumors in the SCID mouse. Thus, in this system, it is the cellular milieu that is crucial in determining whether a given lymphoblastoid cell will give rise to a tumor, not the EBV isolate harbored by the cell or whether the virus is permitted to undergo lytic replication.
Insights
The cellular environment, not Epstein-Barr virus (EBV) replication, determines tumor formation in SCID mice. Marmoset cells, permissive for EBV replication, did not form tumors, unlike human cells.
Area of Science:
- Virology
- Immunology
- Oncology
Background:
- Epstein-Barr virus (EBV) is linked to human cancers.
- Marmoset B lymphocytes support EBV lytic replication, unlike human B cells.
- Severe combined immunodeficiency (SCID) mice are susceptible to EBV-induced lymphomagenesis.
Purpose of the Study:
- To investigate the role of the cellular environment versus EBV replication permissiveness in EBV-induced lymphomagenesis.
- To compare tumor formation in SCID mice using human versus marmoset lymphoblastoid cells infected with EBV.
Main Methods:
- SCID mice were inoculated with EBV-infected human and marmoset lymphoblastoid cells.
- Marmoset cells were treated with acyclovir or anti-natural killer cell antibody.
- Human lymphoblastoid cells engineered for lytic EBV replication were also used.
Main Results:
- Marmoset lymphoblastoid cells did not form lymphomas in SCID mice, even with interventions.
- Human lymphoblastoid cells consistently formed lymphomas within 8 weeks.
- Engineered human cells permitting lytic EBV replication also formed tumors.
Conclusions:
- The cellular milieu, not EBV isolate or lytic replication capacity, is critical for lymphomagenesis in this SCID mouse model.
- Host cell permissiveness for EBV lytic replication does not dictate tumor formation.
- SCID mouse models can differentiate the impact of cellular factors on EBV-driven diseases.