Skip to Main content Skip to Navigation
Journal articles

In primary effusion lymphoma cells, MYB transcriptional repression is associated with v-FLIP expression during latent KSHV infection while both v-FLIP and v-GPCR become involved during the lytic cycle.

Abstract : Primary effusion lymphoma (PEL) is a rare, distinct subtype of non-Hodgkin lymphoma, which is associated with Kaposi sarcoma-associated herpesvirus (KSHV) infection. Although MYB levels are high in most neoplastic B cells, we found that, unexpectedly, both PEL cells and uncultured PEL patients' samples contained very low levels of MYB mRNA when compared to B-cell leukaemia samples obtained from KSHV(-) patients. These results were further confirmed at the protein level. Both latent viral FLICE inhibitory protein (v-FLIP) and early lytic viral G protein coupled receptor (v-GPCR) KSHV proteins were found to activate nuclear factor (NF)-kappaB and transrepress a MYB promoter reporter construct. In contrast, a dominant negative inhibitor of NF-kappaB (IkappaB-alpha) mutant prevented v-FLIP and v-GPCR from inhibiting MYB functions while a v-GPCR mutant that was impaired for NF-kappaB activation could not repress the MYB construct. Transduction of a v-FLIP expressing vector or stable transfection of v-GPCR both resulted in a marked downregulation of the endogenous MYB protein expression. However, MYB expression transactivated the lytic switch Replication and Transcription Activator (RTA) promoter in transient transfection assays. Taken together, our results demonstrate that, contrary to a number of other haematological malignancies, MYB expression is not required for PEL cell proliferation. Repressing MYB expression also helps in maintaining the virus in latency.
Document type :
Journal articles
Complete list of metadatas

https://hal-pasteur.archives-ouvertes.fr/pasteur-00364087
Contributor : Mireille Gau <>
Submitted on : Wednesday, February 25, 2009 - 11:27:05 AM
Last modification on : Wednesday, August 19, 2020 - 11:16:58 AM

Links full text

Identifiers

Citation

Vincent Lacoste, Christophe Nicot, Antoine Gessain, Françoise Valensi, Jean Gabarre, et al.. In primary effusion lymphoma cells, MYB transcriptional repression is associated with v-FLIP expression during latent KSHV infection while both v-FLIP and v-GPCR become involved during the lytic cycle.. British Journal of Haematology, Wiley, 2007, 138 (4), pp.487-501. ⟨10.1111/j.1365-2141.2007.06697.x⟩. ⟨pasteur-00364087⟩

Share

Metrics

Record views

506