The Changes of Viral Expression Concomitant with Bcell Maturation

In healthy carriers EBV resides in the memory B-cell compartment, in which the growth program of the virus is not expressed [12, 13]. The origin of these cells is not yet clarified. The in vitro B-cell transformation system has emphasized the establishment of type III pattern upon infection. This is partly due to the growth capacity of Type III cells that readily proliferate in the infected culture, overgrowing thus other EBV-carrier cells. It was proposed that the infection event leads to

Type III protein expression and the various virus-cell phenotypes may represent successive changes with switches occurring concomitantly with maturation stages of the B lymphocyte [6]. However the viral expression in the latent infection of B lymphocytes can be determined directly by the differentiation of the target B-cell at the occasion of infection as well.

According to the model that employs changes in the expression program of the resident viral genome, naive B-cells are infected with EBV and than they express the type III pattern [6]. In healthy individuals such cells are eliminated by the immune response. Escaping cells may enter and differentiate in the germinal centers (GC) of secondary follicles and switch to type I viral expression. We proposed that the expression of LMP-1 in the EBV-carrying GC B-cells is induced by cytokines [20, 21] and is not a consequence of cell differentiation, as proposed by Babcock et al. [22]. When these cells leave the GC, the EBV-encoded proteins are turned off. In the resting memory B-cells the viral genome is retained, but only the non-coding RNAs, EBERs, are detectable, unless the cells become stimulated and enter the mitotic cycle, when EBNA-1 is also expressed [23].

Indeed, cell phenotype-associated changes in the expression of the resident EBV genome have been shown in LCLs, in BL-derived lines and in somatic cell hybrids [11, 24]. Our results with B-CLL cells infected in vitro indicates however that the property of the target cells at the occasion of the infection can also determine the expression of the viral genes [19, 25].

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