title: Alternative capture of noncoding RNAs or protein-coding genes by herpesviruses to alter host T cell function.
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.
authors.affiliation: Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06536, USA.
authors.forename: Yang Eric
authors.initials: YE
authors.lastname: Guo
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06536, USA.
authors.forename: Kasandra J
authors.initials: KJ
authors.lastname: Riley
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06536, USA; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06536, USA.
authors.forename: Akiko
authors.initials: A
authors.lastname: Iwasaki
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06536, USA; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06536, USA. Electronic address: joan.steitz@yale.edu.
authors.forename: Joan A
authors.initials: JA
authors.lastname: Steitz
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001483:Base Sequence; D002144:Callithrix; D004789:Enzyme Activation; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D051380:GRB2 Adaptor Protein / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006567:Herpesvirus 2, Saimiriine / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D059014:High-Throughput Nucleotide Sequencing; D054884:Host-Pathogen Interactions; D006801:Humans; D047468:Immunoprecipitation; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D019169:Jurkat Cells; D037181:Lectins, C-Type / Q000378:metabolism; D008213:Lymphocyte Activation; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D020871:RNA Stability; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism; D017423:Sequence Analysis, RNA; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D013997:Time Factors; D014162:Transfection; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D058851:GPI-Linked Proteins; D051380:GRB2 Adaptor Protein; D007371:Interferon-gamma; D037181:Lectins, C-Type; D035683:MicroRNAs; D020928:Mitogen-Activated Protein Kinases; D022661:RNA, Untranslated; D012367:RNA, Viral; D011948:Receptors, Antigen, T-Cell; D039961:Semaphorins; D000099192:CD69 Antigens; C495948:GRB2 protein, human; C573415:IFNG protein, human; C531388:MIRN27 microRNA, human; C118753:SEMA7A protein, human
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