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

Abstract

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.

• Authors: Gretchen L Bentz, Anjali Bheda-Malge, Ling Wang, Julia Shackelford, Blossom Damania, Joseph S Pagano
• Journal: Virology (Virology) Vol. 448 Pg. 293-302 (Jan 05 2014) ISSN: 1096-0341 [Electronic] United States
• PMID: 24314660 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2013 Published by Elsevier Inc.

Chemical References

• Antigens, Viral
• EBV-associated membrane antigen, Epstein-Barr virus
• Nuclear Proteins
• UCHL1 protein, human
• Viral Matrix Proteins
• latency-associated nuclear antigen
• Ubiquitin Thiolesterase

Topics

• Antigens, Viral (genetics, metabolism)
• Cell Line, Transformed
• Cell Transformation, Viral
• Epstein-Barr Virus Infections (enzymology, genetics, virology)
• Herpesviridae Infections (enzymology, genetics, virology)
• Herpesvirus 4, Human (genetics, metabolism)
• Herpesvirus 8, Human (genetics, metabolism)
• Humans
• Nuclear Proteins (genetics, metabolism)
• Ubiquitin Thiolesterase (genetics, metabolism)
• Up-Regulation
• Viral Matrix Proteins (genetics, metabolism)