Differential regulation of Epstein-Barr virus (EBV) latent gene expression in Burkitt lymphoma cells infected with a recombinant EBV strain.
Epstein-Barr virus (EBV)-negative Burkitt lymphomas (BLs) can be infected in vitro with prototype EBV strains to study how the virus may affect the phenotype of tumor cells. Studies thus far have concentrated on the use of transforming B95-8 and nontransforming P3HR1 strains. Immunological and phenotypic differences between the sublines infected with these two strains were reported. The majority of these differences, if not all, can be attributed to the lack of EBNA-2 coding sequences in the P3HR1 strain. The recent development of a selectable Akata strain has opened up new possibilities for infecting epithelial and T cells as well. We infected five EBV-negative BL lines with the recombinant Akata virus. Our results indicate that the infected cell lines BL28, Ramos, and DG75 express EBNA-1, EBNA-2, and LMP1, the viral proteins associated with type III latency, and use both YUK and QUK splices. In contrast, two EBV-negative variants of Akata and Mutu when reinfected displayed restricted type I latency and expressed only EBNA-1. All clones of infected Mutu cells used the QUK splice exclusively. The usage of Qp was observed in a majority of Akata clones. Some Akata clones, however, were found to have double promoter usage (Qp and C/Wp) but at 4 months after infection did not express EBNA-2. The results demonstrate differential regulation of EBV latency in BLs with the same recombinant viral strain and suggest that the choice of latency type may be cell dependent. The restricted latency observed for infected Akata and Mutu cells indicates that a BL may opt for type I latency in the absence of immune pressure as well.
Trivedi
P
P
Department of Experimental Medicine and Pathology, University of Rome, La Sapienza, 00161 Rome, Italy.
Spinsanti
P
P
Cuomo
L
L
Volpe
M
M
Takada
K
K
Frati
L
L
Faggioni
A
A
D002051:Burkitt Lymphoma; D019309:Epstein-Barr Virus Nuclear Antigens / Q000096:biosynthesis*; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000502:physiology; D006801:Humans; D011401:Promoter Regions, Genetic; D012326:RNA Splicing; D011995:Recombination, Genetic; D014407:Tumor Cells, Cultured; D014763:Viral Matrix Proteins / Q000096:biosynthesis*; D014764:Viral Proteins; D017735:Virus Latency
C402641:EBNA-2 protein, Human herpesvirus 4; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D014763:Viral Matrix Proteins; D014764:Viral Proteins; C417029:EBV-encoded nuclear antigen 1