Silencing of latent membrane protein 2B reduces susceptibility to activation of lytic Epstein-Barr virus in Burkitt's lymphoma Akata cells.
Epstein-Barr virus (EBV) latent membrane protein 2A (LMP2A) blocks B-cell receptor (BCR) signalling after BCR cross-linking to inhibit activation of lytic EBV, and ectopically expressed LMP2B negatively regulates LMP2A. Here, it is demonstrated that silencing of LMP2B in EBV-harbouring Burkitt's lymphoma Akata cells results in reduced expression of EBV immediate-early lytic BZLF1 gene mRNA and late lytic gp350/220 protein upon BCR cross-linking. Similarly, reduction of lytic EBV activation was observed in Akata cells overexpressing LMP2A. In contrast, silencing of LMP2A expression resulted in higher lytic EBV mRNA and protein expression in BCR cross-linked Akata cells. These observations indicate a role for LMP2B distinct from that of LMP2A in regulation of lytic EBV activation in the host cell and support the hypothesis that LMP2B exhibits a negative-regulatory effect on the ability of LMP2A to maintain EBV latency by preventing the switch to lytic replication.
Rechsteiner
Markus P
MP
Experimental Infectious Diseases and Cancer Research, University Children's Hospital of Zurich, Zurich, Switzerland.
Berger
Christoph
C
Experimental Infectious Diseases and Cancer Research, University Children's Hospital of Zurich, Zurich, Switzerland.
Weber
Matthias
M
Experimental Infectious Diseases and Cancer Research, University Children's Hospital of Zurich, Zurich, Switzerland.
Sigrist
Jürg A
JA
Experimental Infectious Diseases and Cancer Research, University Children's Hospital of Zurich, Zurich, Switzerland.
Nadal
David
D
Experimental Infectious Diseases and Cancer Research, University Children's Hospital of Zurich, Zurich, Switzerland.
Bernasconi
Michele
M
Experimental Infectious Diseases and Cancer Research, University Children's Hospital of Zurich, Zurich, Switzerland.
D002051:Burkitt Lymphoma; D045744:Cell Line, Tumor; D015967:Gene Expression Regulation, Viral; D020868:Gene Silencing; D005822:Genetic Vectors; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D014763:Viral Matrix Proteins / Q000235:genetics*; D014775:Virus Activation; D014779:Virus Replication / Q000502:physiology
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins