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

Virology. 2014 Jan 5:448:293-302. doi: 10.1016/j.virol.2013.10.018. Epub 2013 Nov 8.

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.

Keywords: EBV; KSHV; LANA; LMP1; UCH-L1.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

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

Substances

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