Alternative capture of noncoding RNAs or protein-coding genes by herpesviruses to alter host T cell function.
Yang Eric Guo, Kasandra J Riley, Akiko Iwasaki, Joan A Steitz
Author Information
Yang Eric Guo: Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06536, USA.
Kasandra J Riley: Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06536, USA.
Akiko Iwasaki: 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.
Joan A Steitz: 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.
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.
Associated Data
GENBANK | GSE55185
References
Cold Spring Harb Perspect Biol. 2011 Mar 01;3(3):
[PMID: 20719877]
