Biomaterial Database

Human herpesvirus-6 enhances natural killer cell cytotoxicity via IL-15. 1996

L Flamand, and I Stefanescu, and J Menezes

Pediatric Research Center, University of Montreal, Quebec, Canada.

The marked tropism of human herpesvirus-6 (HHV-6) for natural killer (NK) cells and T lymphocytes has led us to investigate the effect of HHV-6 on cellular cytotoxicity. We describe here how HHV-6 infection of peripheral blood mononuclear cells (PBMC) leads to upregulation of their NK cell cytotoxicity. The induction of NK cell activity by HHV-6 was abrogated by monoclonal antibodies (mAbs) to IL-15 but not by mAbs to other cytokines (IFN-alpha, IFN-gamma, TNF-alpha, TNF-beta, IL-2, IL-12) suggesting that IL-15 secreted in response to viral infection was responsible for the observed effect. Furthermore, NK activation by HHV-6 was blocked with mAb to CD122, as well as by human anti-HHV-6 neutralizing antibodies. Using RT-PCR, we were able to detect IL-15 mRNA upregulation in purified monocyte and NK cell preparations. IL-15 protein synthesis was increased in response to HHV-6. Finally, addition of IL-15 to PBMC cultures was found to severely curtail HHV-6 expression. Taken together, our data suggest that enhanced NK activity in response to viral infection represent a natural anti-viral defense mechanism aimed at rapidly eliminating virus-infected cells.

UI	MeSH Term	Description	Entries
D007378	Interleukins	Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli.	Interleukin
D007694	Killer Cells, Natural	Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type.	NK Cells,Natural Killer Cells,Cell, NK,Cell, Natural Killer,Cells, NK,Cells, Natural Killer,Killer Cell, Natural,NK Cell,Natural Killer Cell
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D002478	Cells, Cultured	Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.	Cultured Cells,Cell, Cultured,Cultured Cell
D003602	Cytotoxicity, Immunologic	The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.	Tumoricidal Activity, Immunologic,Immunologic Cytotoxicity,Immunologic Tumoricidal Activities,Immunologic Tumoricidal Activity,Tumoricidal Activities, Immunologic
D006566	Herpesviridae Infections	Virus diseases caused by the HERPESVIRIDAE.	Herpesvirus Infections,B Virus Infection,Infections, Herpesviridae,Infections, Herpesvirus,B Virus Infections,Herpesviridae Infection,Herpesvirus Infection,Infection, B Virus,Infection, Herpesviridae,Infection, Herpesvirus,Infections, B Virus
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001483	Base Sequence	The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.	DNA Sequence,Nucleotide Sequence,RNA Sequence,DNA Sequences,Base Sequences,Nucleotide Sequences,RNA Sequences,Sequence, Base,Sequence, DNA,Sequence, Nucleotide,Sequence, RNA,Sequences, Base,Sequences, DNA,Sequences, Nucleotide,Sequences, RNA
D012333	RNA, Messenger	RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.	Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D015654	Herpesvirus 6, Human	Members of the ROSEOLOVIRUS genus of the Betaherpesvirales subfamily isolated from patients with AIDS and other LYMPHOPROLIFERATIVE DISORDERS. It infects and replicates in fresh and established lines of hematopoietic cells and cells of neural origin. It also appears to alter the activity of NK CELLS. HHV-6; (HBLV) antibodies are elevated in patients with AIDS; SJOGREN'S SYNDROME; SARCOIDOSIS; CHRONIC FATIGUE SYNDROME, and certain malignancies. HHV-6A is the most common cause of EXANTHEMA SUBITUM and has been implicated in encephalitis. When HHV-6 integrates into the host genome it is referred to as ciHVH-6. When such VIRUS INTEGRATION occurs into the germline it is referred to as iciHHV-6.	HBLV,Herpesvirus 6A, Human,Herpesvirus 6B, Human,Human B-Lymphotropic Virus,Chromosomally Integrated Human Herpesvirus 6,Chromosomally Integrated Human Herpesvirus 6A,Chromosomally Integrated Human Herpesvirus 6B,HHV-6,HHV-6A,HHV-6B,HHV6,HHV6A,HHV6B,Human Herpesvirus 6,Human betaherpesvirus 6,Human betaherpesvirus 6A,Human betaherpesvirus 6B,Inherited Chromosomally Integrated Human Herpesvirus 6,Inherited Chromosomally Integrated Human Herpesvirus 6A,Inherited Chromosomally Integrated Human Herpesvirus 6B,ciHHV-6,ciHHV-6A,ciHHV-6B,ciHHV6,ciHHV6A,ciHHV6B,iciHHV-6,iciHHV-6A,iciHHV-6B,iciHHV6,iciHHV6A,iciHHV6B,B-Lymphotropic Virus, Human,B-Lymphotropic Viruses, Human,Human B Lymphotropic Virus,Human B-Lymphotropic Viruses,Human Herpesvirus 6A,Human Herpesvirus 6B,Human betaherpesvirus 6s