K1 and K15 of Kaposi sarcoma-associated herpes virus are functional homologues of latent membrane protein 2A of Epstein-Barr virus

LMP2A of Epstein-Barr virus is a receptor that mimics an activated B cell receptor, BCR. K1 and K15, related receptors of Kaposi sarcoma-associated herpes virus, KSHV, are expressed in virus-associated tumors but their functions are less obvious. We addressed this uncertainty with mutant EBVs encoding the KSHV genes K1 or K15 in lieu of LMP2A and infected primary human B cells with them. K1 and K15 encoded proteins appear to have noncomplementing redundant functions in this model but our findings suggest that both KSHV proteins can replace LMP2A’s key activities contributing to the survival, activation and proliferation of B cells. We infected unsorted B cells with the four virus stocks, wt EBV, K1 EBV, K15 EBV or ΔLMP2A EBV, adjusted to yield similar rates of EBV-activated and growth transformed B cells. Eight days p.i. activated B cells in the lymphocyte gate were collected by FACS sorting and their RNAs analyzed with the aid of the Affymetrix GeneChip Human Gene 1.0 ST Array covering the whole transcriptome of approx. 29,000 annotated human genes. B cell preparations from four different donors were infected and analyzed accordingly.