Control of Epstein-Barr virus reactivation by activated CD40 and viral latent membrane protein 1.
In humans, Epstein-Barr virus (EBV) establishes a persistent latent infection in peripheral resting B lymphocytes. Virus reactivation is highly restricted. Whereas in healthy humans the infection usually is benign, immunocompromised patients show an increased risk for EBV-associated malignancies, accompanied by an increase in virus replication and in the number of virus-infected cells. To search for viral and host factors regulating virus reactivation, we used conditionally EBV-immortalized B cells. We found that CD40-CD40 ligand interaction and the viral mimic of activated CD40, EBV latent membrane protein 1, suppress virus reactivation. Both inhibit anti-IgM or phorbolester-induced transcription of the viral immediate early protein BZLF1, which controls entry into the viral lytic cycle. The finding that latent membrane protein 1 and CD40 contribute to the regulation of latency may have important implications for the balance between EBV and its host in normal as well as in immunocompromised individuals.
Adler
Barbara
B
GSF-National Research Center for Environment and Health, Institute for Clinical Molecular Biology and Tumor Genetics, Marchioninistrasse 25, D-81377 Munich, Germany. b.adler@gsf.de
Schaadt
Eveline
E
Kempkes
Bettina
B
Zimber-Strobl
Ursula
U
Baier
Barbara
B
Bornkamm
Georg W
GW
D001402:B-Lymphocytes / Q000821:virology; D015152:Blotting, Northern; D019013:CD40 Antigens / Q000096:biosynthesis / Q000378:metabolism*; D002460:Cell Line; D002469:Cell Separation; D004268:DNA-Binding Proteins / Q000502:physiology; D005434:Flow Cytometry; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D008024:Ligands; D011485:Protein Binding; D015398:Signal Transduction; D015534:Trans-Activators / Q000502:physiology; D014158:Transcription, Genetic; D014162:Transfection; D014763:Viral Matrix Proteins / Q000378:metabolism*; D014764:Viral Proteins
C063676:BZLF1 protein, Herpesvirus 4, Human; D019013:CD40 Antigens; D004268:DNA-Binding Proteins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D008024:Ligands; D015534:Trans-Activators; D014763:Viral Matrix Proteins; D014764:Viral Proteins