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Epstein-Barr virus binding to CD21 activates the initial viral promoter via NF-kappaB induction.

Sugano N, Chen W, Roberts ML, Cooper NR - J. Exp. Med. (1997)

Bottom Line: Epstein-Barr virus (EBV), an oncogenic human herpesvirus, binds to and infects normal human B lymphocytes via CD21, the CR2 complement receptor.Studies of the mechanisms that enable EBV to infect nonactivated, noncycling B cells provide compelling evidence for a sequence of events in which EBV binding to CD21 on purified resting human B cells rapidly activates the NF-kappaB transcription factor, which, in turn, binds to and mediates transcriptional activation of Wp, the initial viral latent gene promoter.Thus, EBV binding to its cellular receptor on resting B cells triggers an NF-kappaB-dependent intracellular signaling pathway which is required for infection.

View Article: PubMed Central - PubMed

Affiliation: Scripps Research Institute, Department of Immunology, La Jolla, California 92037, USA.

ABSTRACT
Epstein-Barr virus (EBV), an oncogenic human herpesvirus, binds to and infects normal human B lymphocytes via CD21, the CR2 complement receptor. Studies of the mechanisms that enable EBV to infect nonactivated, noncycling B cells provide compelling evidence for a sequence of events in which EBV binding to CD21 on purified resting human B cells rapidly activates the NF-kappaB transcription factor, which, in turn, binds to and mediates transcriptional activation of Wp, the initial viral latent gene promoter. Thus, EBV binding to its cellular receptor on resting B cells triggers an NF-kappaB-dependent intracellular signaling pathway which is required for infection.

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Wp activation early in EBV  infection. (A) Time course of Wp activation. EBV was incubated with resting B  cells and Wp initiated transcription was  evaluated at the designated times by RT  PCR. (B) Effect of calphostin C. Resting  B cells were preincubated with calphostin C (50 nM) for 2 h before EBV addition. 4 h later, transcription of Wp and the  rpL32 housekeeping gene were evaluated by RT PCR.
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Figure 3: Wp activation early in EBV infection. (A) Time course of Wp activation. EBV was incubated with resting B cells and Wp initiated transcription was evaluated at the designated times by RT PCR. (B) Effect of calphostin C. Resting B cells were preincubated with calphostin C (50 nM) for 2 h before EBV addition. 4 h later, transcription of Wp and the rpL32 housekeeping gene were evaluated by RT PCR.

Mentions: Since aspirin inhibited EBNA 2 transcription, we focused on the initial EBNA 2 promoter, Wp, as a potential target for the NF-κB–dependent signaling pathway. EBNA 2 and EBNA leader protein are initially transcribed from Wp, a promoter located in the major long internal repeat (BamH1 W; reference 27). Transcription from Wp does not require new protein synthesis (28). For Wp to represent a target of the signaling pathway, the viral genome must have reached the nucleus and transcriptional activation of Wp must have occurred within the time frame of EBV-induced NF-κB activation. Although viral nucleocapsids are detectable near the nucleus 60 to 90 min after infection (29), EBNA 2 RNA and protein have not been detected until 8–12 h after EBV addition (13, 14). In the present studies, transcription from Wp was evident 3 h after EBV addition to resting B cells by RT PCR (Fig. 3 A), clearly within the time of marked NF-κB activation; in addition, Wp activation was sensitive to 50 nM calphostin C (Fig. 3 B), further implicating the NF-κB signaling pathway. The earlier time frame for viral gene transcription obtained here in comparison to previous studies is undoubtedly explained by the use of the more sensitive RT PCR technique.


Epstein-Barr virus binding to CD21 activates the initial viral promoter via NF-kappaB induction.

Sugano N, Chen W, Roberts ML, Cooper NR - J. Exp. Med. (1997)

Wp activation early in EBV  infection. (A) Time course of Wp activation. EBV was incubated with resting B  cells and Wp initiated transcription was  evaluated at the designated times by RT  PCR. (B) Effect of calphostin C. Resting  B cells were preincubated with calphostin C (50 nM) for 2 h before EBV addition. 4 h later, transcription of Wp and the  rpL32 housekeeping gene were evaluated by RT PCR.
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Figure 3: Wp activation early in EBV infection. (A) Time course of Wp activation. EBV was incubated with resting B cells and Wp initiated transcription was evaluated at the designated times by RT PCR. (B) Effect of calphostin C. Resting B cells were preincubated with calphostin C (50 nM) for 2 h before EBV addition. 4 h later, transcription of Wp and the rpL32 housekeeping gene were evaluated by RT PCR.
Mentions: Since aspirin inhibited EBNA 2 transcription, we focused on the initial EBNA 2 promoter, Wp, as a potential target for the NF-κB–dependent signaling pathway. EBNA 2 and EBNA leader protein are initially transcribed from Wp, a promoter located in the major long internal repeat (BamH1 W; reference 27). Transcription from Wp does not require new protein synthesis (28). For Wp to represent a target of the signaling pathway, the viral genome must have reached the nucleus and transcriptional activation of Wp must have occurred within the time frame of EBV-induced NF-κB activation. Although viral nucleocapsids are detectable near the nucleus 60 to 90 min after infection (29), EBNA 2 RNA and protein have not been detected until 8–12 h after EBV addition (13, 14). In the present studies, transcription from Wp was evident 3 h after EBV addition to resting B cells by RT PCR (Fig. 3 A), clearly within the time of marked NF-κB activation; in addition, Wp activation was sensitive to 50 nM calphostin C (Fig. 3 B), further implicating the NF-κB signaling pathway. The earlier time frame for viral gene transcription obtained here in comparison to previous studies is undoubtedly explained by the use of the more sensitive RT PCR technique.

Bottom Line: Epstein-Barr virus (EBV), an oncogenic human herpesvirus, binds to and infects normal human B lymphocytes via CD21, the CR2 complement receptor.Studies of the mechanisms that enable EBV to infect nonactivated, noncycling B cells provide compelling evidence for a sequence of events in which EBV binding to CD21 on purified resting human B cells rapidly activates the NF-kappaB transcription factor, which, in turn, binds to and mediates transcriptional activation of Wp, the initial viral latent gene promoter.Thus, EBV binding to its cellular receptor on resting B cells triggers an NF-kappaB-dependent intracellular signaling pathway which is required for infection.

View Article: PubMed Central - PubMed

Affiliation: Scripps Research Institute, Department of Immunology, La Jolla, California 92037, USA.

ABSTRACT
Epstein-Barr virus (EBV), an oncogenic human herpesvirus, binds to and infects normal human B lymphocytes via CD21, the CR2 complement receptor. Studies of the mechanisms that enable EBV to infect nonactivated, noncycling B cells provide compelling evidence for a sequence of events in which EBV binding to CD21 on purified resting human B cells rapidly activates the NF-kappaB transcription factor, which, in turn, binds to and mediates transcriptional activation of Wp, the initial viral latent gene promoter. Thus, EBV binding to its cellular receptor on resting B cells triggers an NF-kappaB-dependent intracellular signaling pathway which is required for infection.

Show MeSH
Related in: MedlinePlus