Small nuclear RNAs encoded by Herpesvirus saimiri upregulate the expression of genes linked to T cell activation in virally transformed T cells

Curr Biol. 2005 May 24;15(10):974-9. doi: 10.1016/j.cub.2005.04.034.

Abstract

Seven small nuclear RNAs of the Sm class are encoded by Herpesvirus saimiri (HVS), a gamma Herpesvirus that causes aggressive T cell leukemias and lymphomas in New World primates and efficiently transforms T cells in vitro. The Herpesvirus saimiri U RNAs (HSURs) are the most abundant viral transcripts in HVS-transformed, latently infected T cells but are not required for viral replication or transformation in vitro. We have compared marmoset T cells transformed with wild-type or a mutant HVS lacking the most highly conserved HSURs, HSURs 1 and 2. Microarray and Northern analyses reveal that HSUR 1 and 2 expression correlates with significant increases in a small number of host mRNAs, including the T cell-receptor beta and gamma chains, the T cell and natural killer (NK) cell-surface receptors CD52 and DAP10, and intracellular proteins--SKAP55, granulysin, and NKG7--linked to T cell and NK cell activation. Upregulation of three of these transcripts was rescued after transduction of deletion-mutant-HVS-transformed cells with a lentiviral vector carrying HSURs 1 and 2. These changes indicate an unexpected role for the HSURs in regulating a remarkably defined and physiologically relevant set of host targets involved in the activation of virally transformed T cells during latency.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • Antigens, Neoplasm / metabolism
  • Base Pairing
  • Blotting, Northern
  • Blotting, Western
  • CD52 Antigen
  • Callithrix
  • Cell Line, Tumor
  • Flow Cytometry
  • Genetic Vectors
  • Genome, Viral*
  • Glycoproteins / metabolism
  • Herpesvirus 2, Saimiriine / genetics
  • Herpesvirus 2, Saimiriine / metabolism*
  • Lentivirus
  • Lymphocyte Activation / genetics*
  • Lymphocyte Activation / physiology
  • Membrane Proteins / metabolism
  • Microarray Analysis
  • Oncogene Proteins, Viral / metabolism
  • RNA, Small Nuclear / genetics
  • RNA, Small Nuclear / metabolism*
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Immunologic / metabolism
  • T-Lymphocytes / physiology*
  • Transduction, Genetic
  • Up-Regulation / genetics*

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • Antigens, Neoplasm
  • CD52 Antigen
  • CD52 protein, human
  • GNLY protein, human
  • Glycoproteins
  • HCST protein, human
  • Membrane Proteins
  • Oncogene Proteins, Viral
  • RNA, Small Nuclear
  • Receptors, Antigen, T-Cell
  • Receptors, Immunologic
  • STP protein, Herpesvirus saimiri