20980506
not annotated - annotated - LINNAEUS only
A new model of Epstein-Barr virus infection reveals an important role for earlylytic viral protein expression in the development of lymphomas.
Epstein-Barr virus (EBV) infects cells in latent or lytic forms, but the roleof lytic infection in EBV-induced lymphomas is unclear. Here, we have used anew humanized mouse model, in which both human fetal CD34(+) hematopoietic stemcells and thymus/liver tissue are transplanted, to compare EBV pathogenesis andlymphoma formation following infection with a lytic replication-defectiveBZLF1-deleted (Z-KO) virus or a lytically active BZLF1(+) control. Both thecontrol and Z-KO viruses established long-term viral latency in all infectedanimals. The infection appeared well controlled in some animals, but otherseventually developed CD20(+) diffuse large B cell lymphomas (DLBCL). Animalsinfected with the control virus developed tumors more frequently than Z-KOvirus-infected animals. Specific immune responses against EBV-infected B cellswere generated in mice infected with either the control virus or the Z-KOvirus. In both cases, forms of viral latency (type I and type IIB) wereobserved that are less immunogenic than the highly transforming form (type III)commonly found in tumors of immunocompromised hosts, suggesting that immunepressure contributed to the outcome of the infection. These results point to animportant role for lytic EBV infection in the development of B cell lymphomasin the context of an active host immune response.
Ann file
T1 Species 15 33 Epstein-Barr virus
N1 Reference T1 Taxonomy:10376
T2 Species 144 162 Epstein-Barr virus
N2 Reference T2 Taxonomy:10376
T3 Species 164 167 EBV
N3 Reference T3 Taxonomy:10376
T4 Species 243 246 EBV
N4 Reference T4 Taxonomy:10376
T5 Species 311 316 mouse
N5 Reference T5 Taxonomy:10090
T6 Species 338 343 human
N6 Reference T6 Taxonomy:9606
T7 Species 435 438 EBV
N7 Reference T7 Taxonomy:10376
T8 Species 962 965 EBV
N8 Reference T8 Taxonomy:10376
T9 Species 1000 1004 mice
N9 Reference T9 Taxonomy:10090
T10 Species 1384 1387 EBV
N10 Reference T10 Taxonomy:10376