Biomaterial Database

Activation of the Epstein-Barr virus replicative cycle by human herpesvirus 6. 1993

L Flamand, and I Stefanescu, and D V Ablashi, and J Menezes

Laboratory of Immunovirology, Ste-Justine Hospital, Montreal, Canada.

One common attribute of herpesviruses is the ability to establish latent, life-long infections. The role of virus-virus interaction in viral reactivation between or among herpesviruses has not been studied. Preliminary experiments in our laboratory had indicated that infection of Epstein-Barr virus (EBV) genome-positive human lymphoid cell lines with human herpesvirus 6 (HHV-6) results in EBV reactivation in these cells. To further our knowledge of this complex phenomenon, we investigated the effect of HHV-6 infection on expression of the viral lytic cycle proteins of EBV. Our results indicate that HHV-6 upregulates, by up to 10-fold, expression of the immediate-early Zebra antigen and the diffuse and restricted (85 kDa) early antigens (EA-D and EA-R, respectively) in both EBV producer and nonproducer cell lines (i.e., P3HR1, Akata, and Raji). Maximal EA-D induction was observed at 72 h post-HHV-6 infection. Furthermore, expression of late EBV gene products, namely, the viral capsid antigen (125 kDa) and viral membrane glycoprotein gp350, was also increased in EBV producer cells (P3HR1 and Akata) following infection by HHV-6. By using dual-color membrane immunofluorescence, it was found that most of the cells expressing viral membrane glycoprotein gp350 were also positive for HHV-6 antigens, suggesting a direct effect of HHV-6 replication on induction of the EBV replicative cycle. No expression of late EBV antigens was observed in Raji cells following infection by HHV-6, implying a lack of functional complementation between the deleted form of EBV found in Raji cells and the superinfecting HHV-6. The susceptibility of the cell lines to infection by HHV-6 correlated with increased expression of various EBV proteins in that B95-8 cells, which are not susceptible to HHV-6 infection, did not show an increase in expression of EBV antigens following treatment with HHV-6. Moreover, UV light-irradiated or heat-inactivated HHV-6 had no upregulating effect on the Zebra antigen or EA-D in Raji cells, indicating that infectious virus is required for the observed effects of HHV-6 on these EBV products. These results show that HHV-6, another lymphotropic human herpesvirus, can activate EBV replication and may thus contribute to the pathogenesis of EBV-associated diseases.

UI	MeSH Term	Description	Entries
D008562	Membrane Glycoproteins	Glycoproteins found on the membrane or surface of cells.	Cell Surface Glycoproteins,Surface Glycoproteins,Cell Surface Glycoprotein,Membrane Glycoprotein,Surface Glycoprotein,Glycoprotein, Cell Surface,Glycoprotein, Membrane,Glycoprotein, Surface,Glycoproteins, Cell Surface,Glycoproteins, Membrane,Glycoproteins, Surface,Surface Glycoprotein, Cell,Surface Glycoproteins, Cell
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D004268	DNA-Binding Proteins	Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.	DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D004854	Herpesvirus 4, Human	The type species of LYMPHOCRYPTOVIRUS, subfamily GAMMAHERPESVIRINAE, infecting B-cells in humans. It is thought to be the causative agent of INFECTIOUS MONONUCLEOSIS and is strongly associated with oral hairy leukoplakia (LEUKOPLAKIA, HAIRY;), BURKITT LYMPHOMA; and other malignancies.	Burkitt Herpesvirus,Burkitt Lymphoma Virus,E-B Virus,EBV,Epstein-Barr Virus,Human Herpesvirus 4,Infectious Mononucleosis Virus,Burkitt's Lymphoma Virus,HHV-4,Herpesvirus 4 (gamma), Human,Burkitts Lymphoma Virus,E B Virus,E-B Viruses,Epstein Barr Virus,Herpesvirus, Burkitt,Infectious Mononucleosis Viruses,Lymphoma Virus, Burkitt,Mononucleosis Virus, Infectious,Mononucleosis Viruses, Infectious
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000956	Antigens, Viral	Substances elaborated by viruses that have antigenic activity.	Viral Antigen,Viral Antigens,Antigen, Viral
D014764	Viral Proteins	Proteins found in any species of virus.	Gene Products, Viral,Viral Gene Products,Viral Gene Proteins,Viral Protein,Protein, Viral,Proteins, Viral
D014779	Virus Replication	The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle.	Viral Replication,Replication, Viral,Replication, Virus,Replications, Viral,Replications, Virus,Viral Replications,Virus Replications
D015534	Trans-Activators	Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.	Nuclear Trans-Acting Factor,Trans-Acting Factors,Trans-Acting Factor,Trans-Activator,Transactivator,Transactivators,Factor, Nuclear Trans-Acting,Factor, Trans-Acting,Factors, Trans-Acting,Nuclear Trans Acting Factor,Trans Acting Factor,Trans Acting Factors,Trans Activator,Trans Activators,Trans-Acting Factor, Nuclear
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