Table 1.
Specific patterns of EBV gene expression during the latent phase of infection and their association with malignancies and MS.
| Latency Program | Alternative Name | Gene Products 1 | Site In Vivo | Stage of Normal B-Cell Development | Events | Biomarkers | Associated Disease 1,2 | Ref |
|---|---|---|---|---|---|---|---|---|
| 0 | Latency program 0 | EBERs BART microRNAs (non-coding genes) |
Peripheral circulation | Latently infected memory B cells | Downregulation of most viral protein-encoding genes suppressing the production of virions | None | None | [37] |
| I | Latency program I |
EBNA1 3 EBER1/2 RNA BART microRNAs |
Peripheral circulation | The homeostatic proliferation of memory B cells is not driven by the virus | Replication of EBV genome harnessing the mitotic cycle of memory B cells | Anti-EBNA1 IgG Anti-VCA IgG |
BL | [42] |
| II | Default program |
EBNA1 3 EBER1/2 RNA BART microRNAs LMP1 LMP2A/B |
Tonsil germinal center (GC) and lymph nodes | Naïve B cells infected by EBV gain access into the GC for the normal process of differentiation | EBV set a limited transcriptional program that rescues EBV-DNA into the memory B cell compartment where viral DNA persists as the episome | Anti-EBNA1 IgG Anti-VCA IgG |
HL T/NK-cell malignancies Epithelial malignancies NFC |
[41,51,52] |
| III | Growth program |
EBNA1 3 EBNA2 EBNA3A, 3B, 3C EBER1/2 RNA EBNALP BART microRNAs LMP1 LMP2A/B |
Tonsil GC/Lymph nodes | Activation of naïve B cells infected by EBV In this lytic phase, B cells become proliferating B-blasts before entering the GC |
Full expression of EBV proteins CTL trigger a strong immune response to suppress EBV-infected B cells Selective silencing of EBV genes upon unknown individual and environmental conditions |
Anti-EA IgM Anti-EBNA1 &-2 IgM Anti-VCA IgM/IgG CTL |
DLBCL Post-transplant lymphoproliferative disorders CNS lymphoma MS? |
[41,42,47,52] |
1 See the glossary section for abbreviations. 2 EBV-gene expression is tightly regulated in a tissue-specific manner. 3 EBNA1 is expressed from promoter Qp in the latency programs I/II and from the Cp promoter in the growth program III from the EBV’s circular shaped DNA inside the cell nucleus (episome). This protein allows the viral genome to replicate at the same time with the host cell. The main gene transcripts of EBV are shown in bold letters.