title: Upregulation of Epstein-Barr virus-encoded latent membrane protein by human herpesvirus 6 superinfection of EBV-carrying Burkitt lymphoma cells.
abstract: The effect of HHV-6 strain A infection on the expression of Epstein-Barr virus- (EBV-) encoded growth transformation-associated genes in two EBV-positive Burkitt lymphoma cell lines, Akata and P3HR-3, was investigated. The results indicate that HHV-6A upregulates the expression of the latent membrane protein LMP-1 in both cell lines. Expression of EBNA-2 was also upregulated in Akata cells following HHV-6A infection. Transfection of reporter constructs carrying the LMP-1 regulatory sequences (LRS; -634/+40) or its 5' deleted derivatives in Akata and in a T-lymphoblastoid cell line, J-Jhan, confirmed the presence of positive and negative regulatory elements responsive to HHV-6A infection in LMP-1 regulatory sequence (LRS). The majority of LRS constructs were under the influence of dominant negative factors. HHV-6A was able to override the effect of such factors acting on reporter plasmids containing the -634/-54, -324/-54, -214/-54, and -106/-54 parts of LRS. The plasmid that carried only the -54/+40 LRS region was constitutively active in both Akata and J-Jhan cells; in Akata, its activity was influenced by HHV-6A. The finding that HHV-6A infection may activate LMP-1 and EBNA-2 expression, which is essential for the immortalization of B-lymphocytes by EBV, shows a novel aspect of the interaction between these two herpesviruses.
authors.affiliation: Istituto Neurologico Mediterraneo Neuromed, Pozzilli, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Cuomo
authors.forename: P
authors.initials: P
authors.lastname: Trivedi
authors.forename: U
authors.initials: U
authors.lastname: de Grazia
authors.forename: A
authors.initials: A
authors.lastname: Calogero
authors.forename: M
authors.initials: M
authors.lastname: D'Onofrio
authors.forename: W
authors.initials: W
authors.lastname: Yang
authors.forename: L
authors.initials: L
authors.lastname: Frati
authors.forename: A
authors.initials: A
authors.lastname: Faggioni
authors.forename: L
authors.initials: L
authors.lastname: Rymo
authors.forename: G
authors.initials: G
authors.lastname: Ragona
mesh_terms: D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D002051:Burkitt Lymphoma / Q000821:virology*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000096:biosynthesis / Q000235:genetics; D005455:Fluorescent Antibody Technique; D015967:Gene Expression Regulation, Viral; D005814:Genes, Viral; D006566:Herpesviridae Infections / Q000821:virology*; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D015654:Herpesvirus 6, Human / Q000502:physiology*; D006801:Humans; D010746:Phosphonoacetic Acid / Q000494:pharmacology; D010957:Plasmids; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D015163:Superinfection / Q000821:virology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D014763:Viral Matrix Proteins / Q000096:biosynthesis / Q000235:genetics*; D017735:Virus Latency
chemical_list: D000911:Antibodies, Monoclonal; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D014763:Viral Matrix Proteins; D010746:Phosphonoacetic Acid