The latent membrane protein 1 of Epstein-Barr virus establishes an antiviral state via induction of interferon-stimulated genes.
Epstein-Barr virus (EBV) infection is associated with several human cancers. Latent membrane protein 1 (LMP-1) is one of the key viral proteins required for transformation of primary B cells in vitro and establishment of EBV latency. In this report, we show that LMP-1 is able to induce the expression of several interferon (IFN)-stimulated genes (ISGs) with antiviral properties such as 2'-5' oligoadenylate synthetase (OAS), stimulated trans-acting factor of 50 kDa (STAF-50), and ISG-15. LMP-1 inhibits vesicular stomatitis virus (VSV) replication at low multiplicity of infection (0.1 pfu/cell). The antiviral effect of LMP-1 is associated with the ability of LMP-1 to induce ISGs; an LMP-1 mutant that cannot induce ISGs fails to induce an antiviral state. High levels of ISGs are expressed in EBV latency cells in which LMP-1 is expressed. EBV latency cells have antiviral activity that inhibits replication of superinfecting VSV. The antiviral activity of LMP-1 is apparently not related to IFN production in our experimental systems. In addition, EBV latency is responsive to viral superinfection: LMP-1 is induced and EBV latency is disrupted by EBV lytic replication during VSV superinfection of EBV latency cells. These data suggest that LMP-1 has antiviral effect, which may be an intrinsic part of EBV latency program to assist the establishment and/or maintenance of EBV latency.
Zhang
Jun
J
Nebraska Center for Virology, University of Nebraska, Lincoln, NE 68588, USA.
Das
Subash C
SC
Kotalik
Catherine
C
Pattnaik
Asit K
AK
Zhang
Luwen
L
D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D050839:Interferon Regulatory Factor-7; D007372:Interferons / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000235:genetics; D015778:Minor Histocompatibility Antigens; D012097:Repressor Proteins / Q000235:genetics*; D050794:STAT1 Transcription Factor; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D000070584:Tripartite Motif Proteins; D014721:Vesicular stomatitis Indiana virus / Q000502:physiology; D014759:Viral Envelope Proteins / Q000235:genetics; D014763:Viral Matrix Proteins / Q000502:physiology*; D017735:Virus Latency; D014779:Virus Replication
D004268:DNA-Binding Proteins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; C028391:G protein, vesicular stomatitis virus; C494234:IRF7 protein, human; D050839:Interferon Regulatory Factor-7; D008562:Membrane Glycoproteins; D015778:Minor Histocompatibility Antigens; D012097:Repressor Proteins; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C094314:TRIM22 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000070584:Tripartite Motif Proteins; D014759:Viral Envelope Proteins; D014763:Viral Matrix Proteins; D007372:Interferons; D015088:2',5'-Oligoadenylate Synthetase