Dataset Information

A herpesvirus saimiri membrane protein required for interleukin-2 independence forms a stable complex with p56lck.

ABSTRACT: ORF-2, a 32-kDa viral protein expressed by herpesvirus saimiri-transformed lymphocytes, is essential for transformation and is expressed on the plasma membrane of transformed cells. The current work now shows that most (approximately 80%) of ORF-2 resides in the cytoplasm, while only a small portion protrudes from the cell surface. Expressed as a glutathione S-transferase fusion protein, ORF-2 was found to interact with a 56-kDa cellular protein in untransformed, herpesvirus saimiri-transformed, and Jurkat lymphocytes. Microsequencing proved that this protein is the lymphocyte-specific tyrosine protein kinase p56lck. Two regions of ORF-2 were found to be required for p56lck interaction. Current evidence suggests that the interaction of ORF-2 with p56lck plays a key role in the specific transformation of T lymphocytes to an interleukin-2-independent phenotype.

SUBMITTER: Lund T

PROVIDER: S-EPMC189852 | biostudies-other | 1996 Jan

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

A herpesvirus saimiri membrane protein required for interleukin-2 independence forms a stable complex with p56lck.

Lund T T Medveczky M M MM Neame P J PJ Medveczky P G PG

Journal of virology 19960101 1

ORF-2, a 32-kDa viral protein expressed by herpesvirus saimiri-transformed lymphocytes, is essential for transformation and is expressed on the plasma membrane of transformed cells. The current work now shows that most (approximately 80%) of ORF-2 resides in the cytoplasm, while only a small portion protrudes from the cell surface. Expressed as a glutathione S-transferase fusion protein, ORF-2 was found to interact with a 56-kDa cellular protein in untransformed, herpesvirus saimiri-transformed, ...[more]

PMID: 8523578

Similar Datasets

Project description:UnlabelledIn latently infected marmoset T cells, Herpesvirus saimiri (HVS) expresses six microRNAs (known as miR-HSURs [H. saimiri U-rich RNAs]). The viral miR-HSURs are processed from chimeric primary transcripts, each containing a noncoding U-rich RNA (HSUR) and a pre-miRNA hairpin. To uncover the functions of miR-HSURs, we identified mRNA targets in infected cells using high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation (HITS-CLIP). HITS-CLIP revealed hundreds of robust Argonaute (Ago) binding sites mediated by miR-HSURs that map to the host genome but few in the HVS genome. Gene ontology analysis showed that several pathways regulating the cell cycle are enriched among cellular targets of miR-HSURs. Interestingly, miR-HSUR4-3p represses expression of the p300 transcriptional coactivator by binding the open reading frame of its mRNA. miR-HSUR5-3p directly regulates BiP, an endoplasmic reticulum (ER)-localized chaperone facilitating maturation of major histocompatibility complex class I (MHC-I) and the antiviral response. miR-HSUR5-3p also robustly downregulates WEE1, a key negative regulator of cell cycle progression, leading to reduced phosphorylation of its substrate, cyclin-dependent kinase (Cdk1). Consistently, inhibition of miR-HSUR5-3p in HVS-infected cells decreases their proliferation. Together, our results shed light on the roles of viral miRNAs in cellular transformation and viral latency.ImportanceViruses express miRNAs during various stages of infection, suggesting that viral miRNAs play critical roles in the viral life cycle. Compared to protein-coding genes, the functions of viral miRNAs are not well understood. This is because it has been challenging to identify their mRNA targets. Here, we focused on the functions of the recently discovered HVS miRNAs, called miR-HSURs. HVS is an oncogenic gammaherpesvirus that causes acute T-cell lymphomas and leukemias in New World primates and transforms human T cells. A better understanding of HVS biology will help advance our knowledge of virus-induced oncogenesis. Because numerous cellular miRNAs play crucial roles in cancer, viral miRNAs from the highly oncogenic HVS might also be important for transformation. Here, we found that the miR-HSURs preferentially modulate expression of host cell cycle regulators, as well as antiviral response factors. Our work provides further insight into the functions of herpesviral miRNAs in virus-induced oncogenesis and latency.

Dataset Information

A herpesvirus saimiri membrane protein required for interleukin-2 independence forms a stable complex with p56lck.

Publications

A herpesvirus saimiri membrane protein required for interleukin-2 independence forms a stable complex with p56lck.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets