Alternative capture of noncoding RNAs or protein-coding genes by herpesviruses to alter host T cell function

Mol Cell. 2014 Apr 10;54(1):67-79. doi: 10.1016/j.molcel.2014.03.025.

Abstract

In marmoset T cells transformed by Herpesvirus saimiri (HVS), a viral U-rich noncoding (nc) RNA, HSUR 1, specifically mediates degradation of host microRNA-27 (miR-27). High-throughput sequencing of RNA after crosslinking immunoprecipitation (HITS-CLIP) identified mRNAs targeted by miR-27 as enriched in the T cell receptor (TCR) signaling pathway, including GRB2. Accordingly, transfection of miR-27 into human T cells attenuates TCR-induced activation of mitogen-activated protein kinases (MAPKs) and induction of CD69. MiR-27 also robustly regulates SEMA7A and IFN-γ, key modulators and effectors of T cell function. Knockdown or ectopic expression of HSUR 1 alters levels of these proteins in virally transformed cells. Two other T-lymphotropic γ-herpesviruses, AlHV-1 and OvHV-2, do not produce a noncoding RNA to downregulate miR-27 but instead encode homologs of miR-27 target genes. Thus, oncogenic γ-herpesviruses have evolved diverse strategies to converge on common targets in host T cells.

Publication types

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

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • Base Sequence
  • Callithrix
  • Enzyme Activation
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • GRB2 Adaptor Protein / genetics
  • GRB2 Adaptor Protein / metabolism
  • Gene Expression Regulation
  • HEK293 Cells
  • Herpesvirus 2, Saimiriine / genetics
  • Herpesvirus 2, Saimiriine / metabolism*
  • Herpesvirus 2, Saimiriine / pathogenicity
  • High-Throughput Nucleotide Sequencing
  • Host-Pathogen Interactions
  • Humans
  • Immunoprecipitation
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Jurkat Cells
  • Lectins, C-Type / metabolism
  • Lymphocyte Activation*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Mitogen-Activated Protein Kinases / metabolism
  • Molecular Sequence Data
  • RNA Stability
  • RNA, Untranslated / genetics
  • RNA, Untranslated / metabolism*
  • RNA, Viral / genetics
  • RNA, Viral / metabolism*
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism
  • Semaphorins / genetics
  • Semaphorins / metabolism
  • Sequence Analysis, RNA
  • Signal Transduction
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / virology
  • Time Factors
  • Transfection

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • GPI-Linked Proteins
  • GRB2 Adaptor Protein
  • GRB2 protein, human
  • IFNG protein, human
  • Lectins, C-Type
  • MIRN27 microRNA, human
  • MicroRNAs
  • RNA, Untranslated
  • RNA, Viral
  • Receptors, Antigen, T-Cell
  • SEMA7A protein, human
  • Semaphorins
  • Interferon-gamma
  • Mitogen-Activated Protein Kinases

Associated data

  • GENBANK/GSE55185