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

TY - JOUR

T1 - Small nuclear RNAs encoded by Herpesvirus saimiri upregulate the expression of genes linked to T cell activation in virally transformed T cells

AU - Cook, Heidi L

AU - Lytle, J Robin

AU - Mischo, Hannah E

AU - Li, Ming-Jie

AU - Rossi, John J

AU - Silva, Daniel P

AU - Desrosiers, Ronald C

AU - Steitz, Joan A

PY - 2005/5/24

Y1 - 2005/5/24

N2 - 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.

AB - 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.

KW - Animals

KW - Antigens, CD/metabolism

KW - Antigens, Differentiation, T-Lymphocyte/metabolism

KW - Antigens, Neoplasm/metabolism

KW - Base Pairing

KW - Blotting, Northern

KW - Blotting, Western

KW - CD52 Antigen

KW - Callithrix

KW - Cell Line, Tumor

KW - Flow Cytometry

KW - Genetic Vectors

KW - Genome, Viral

KW - Glycoproteins/metabolism

KW - Herpesvirus 2, Saimiriine/genetics

KW - Lentivirus

KW - Lymphocyte Activation/genetics

KW - Membrane Proteins/metabolism

KW - Microarray Analysis

KW - Oncogene Proteins, Viral/metabolism

KW - RNA, Small Nuclear/genetics

KW - Receptors, Antigen, T-Cell/metabolism

KW - Receptors, Immunologic/metabolism

KW - T-Lymphocytes/physiology

KW - Transduction, Genetic

KW - Up-Regulation/genetics

U2 - 10.1016/j.cub.2005.04.034

DO - 10.1016/j.cub.2005.04.034

M3 - Article

C2 - 15916956

SN - 0960-9822

VL - 15

SP - 974

EP - 979

JO - Current biology : CB

JF - Current biology : CB

IS - 10

ER -