Small nuclear RNAs encoded by Herpesvirus saimiri upregulate the expression of genes linked to T cell activation in virally transformed T cells.
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.
Cook
Heidi L
HL
Howard Hughes Medical Institute, Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06536, USA.
Lytle
J Robin
JR
Mischo
Hannah E
HE
Li
Ming-Jie
MJ
Rossi
John J
JJ
Silva
Daniel P
DP
Desrosiers
Ronald C
RC
Steitz
Joan A
JA
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D000951:Antigens, Neoplasm / Q000378:metabolism; D020029:Base Pairing; D015152:Blotting, Northern; D015153:Blotting, Western; D000074301:CD52 Antigen; D002144:Callithrix; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D005822:Genetic Vectors; D016679:Genome, Viral; D006023:Glycoproteins / Q000378:metabolism; D006567:Herpesvirus 2, Saimiriine / Q000235:genetics / Q000378:metabolism*; D016086:Lentivirus; D008213:Lymphocyte Activation / Q000235:genetics* / Q000502:physiology; D008565:Membrane Proteins / Q000378:metabolism; D046228:Microarray Analysis; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D012342:RNA, Small Nuclear / Q000235:genetics / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology*; D014161:Transduction, Genetic; D015854:Up-Regulation / Q000235:genetics*
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D000074301:CD52 Antigen; C000613862:CD52 protein, human; C075005:GNLY protein, human; D006023:Glycoproteins; C120528:HCST protein, human; D008565:Membrane Proteins; D009856:Oncogene Proteins, Viral; D012342:RNA, Small Nuclear; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; C064364:STP protein, Herpesvirus saimiri