KSHV LANA and EBV LMP1 induce the expression of UCH-L1 following viral transformation

- Infection of endothelial cells with KSHV induced UCH-L1 expression.
- KSHV LANA is sufficient for the induction of uch-l1.
- Co-infection with KSHV and EBV (observed in some PELs) results in the additive induction of uch-l1.
- EBV LMP1 also induced UCH-L1 expression.
- LANA- and LMP1-mediated activation of the uch-l1 promoter is in part through RBP-Jκ

Ubiquitin C-terminal Hydrolase L1 (UCH-L1) has oncogenic properties and is highly expressed during malignancies. We recently documented that Epstein-Barr virus (EBV) infection induces uch-l1 expression. Here we show that Kaposi's Sarcoma-associated herpesvirus (KSHV) infection induced UCH-L1 expression, via cooperation of KSHV Latency-Associated Nuclear Antigen (LANA) and RBP-Jκ and activation of the uch-l1 promoter. UCH-L1 expression was also increased in Primary Effusion Lymphoma (PEL) cells co-infected with KSHV and EBV compared with PEL cells infected only with KSHV, suggesting EBV augments the effect of LANA on uch-l1. EBV latent membrane protein 1 (LMP1) is one of the few EBV products expressed in PEL cells. Results showed that LMP1 was sufficient to induce uch-l1 expression, and co-expression of LMP1 and LANA had an additive effect on uch-l1 expression. These results indicate that viral latency products of both human γ-herpesviruses contribute to uch-l1 expression, which may contribute to the progression of lymphoid malignancies.