Latent membrane protein 1 inhibits Epstein-Barr virus lytic cycle induction and progress via different mechanisms.
Epstein-Barr virus (EBV) is a potent growth-transforming agent of human B cells. It has previously been shown that viral latent membrane protein 1 (LMP1) is essential for EBV-induced transformation of normal B cells and contributes to maintenance of latency in vitro. Using the EBV-positive Burkitt's lymphoma line P3HR1-c16, which lacks LMP1 during latency and which can readily be activated into virus-productive lytic cycle, we found that LMP1 inhibits lytic cycle induction via the transcription factor NF-kappa B. In addition, LMP1 inhibits lytic cycle progress via two distinct NF-kappa B-independent mechanisms: one involving the cytosolic C-terminal activating regions and the other involving the transmembrane region of LMP1. These findings indicate that in B cells EBV self-limits its lytic cycle via three distinct LMP1-mediated mechanisms.
Prince
Stuart
S
Section of Infection and Immunity, University of Wales College of Medicine, Cardiff CF14 4XX, United Kingdom.
Keating
Sinead
S
Fielding
Ceri
C
Brennan
Paul
P
Floettmann
Eike
E
Rowe
Martin
M
D001402:B-Lymphocytes / Q000821:virology; D002051:Burkitt Lymphoma; D002461:Cell Line, Transformed; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D014775:Virus Activation / Q000187:drug effects*; D017735:Virus Latency
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D016328:NF-kappa B; D014763:Viral Matrix Proteins