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Viral induction of AID is independent of the interferon and the Toll-like receptor signaling pathways but requires NF-kappaB.

Gourzi P, Leonova T, Papavasiliou FN - J. Exp. Med. (2007)

Bottom Line: Here we show that AID is not an interferon responsive gene and abrogation of Toll-like receptor signaling does not diminish the AID response.However, we found that NF-kappaB was required for expression of virally induced AID.Since NF-kappaB binds and activates the AID promoter, these results mechanistically link viral infection with AID transcription.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Lymphocyte Biology, The Rockefeller University, New York, NY 10021, USA.

ABSTRACT
Activation-induced cytidine deaminase (AID) is expressed in germinal centers of lymphoid organs during immunoglobulin diversification, in bone marrow B cells after infection with Abelson murine leukemia retrovirus (Ab-MLV), and in human B cells after infection by hepatitis C virus. To understand how viruses signal AID induction in the host we asked whether the AID response was abrogated in cells deficient in the interferon pathway or in signaling via the Toll-like receptors. Here we show that AID is not an interferon responsive gene and abrogation of Toll-like receptor signaling does not diminish the AID response. However, we found that NF-kappaB was required for expression of virally induced AID. Since NF-kappaB binds and activates the AID promoter, these results mechanistically link viral infection with AID transcription. Thus, induction of AID by viruses could be the result of several signaling pathways that culminate in NF-kappaB activation, underscoring the versatility of this host defense program.

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AID up-regulation does not require intact IFN signaling. (A) Mo-MLV infection of mouse bone marrow results in AID upregulation. CD79b expression is a loading control for the RT-PCR reaction. (B) IFN-γ and IFN-αR–deficient bone marrow cells induce AID expression upon viral infection.
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fig1: AID up-regulation does not require intact IFN signaling. (A) Mo-MLV infection of mouse bone marrow results in AID upregulation. CD79b expression is a loading control for the RT-PCR reaction. (B) IFN-γ and IFN-αR–deficient bone marrow cells induce AID expression upon viral infection.

Mentions: To determine the signaling cascade that induces AID expression in Ab-MLV–infected cells, we first asked whether it required the v-abl kinase, which is the single protein product made by the retrovirus and the cause of transformation. We therefore infected cells with the highly related Moloney murine leukemia virus (Mo-MLV), which does not encode the v-abl kinase. We found that Mo-MLV infection of bone marrow cells resulted in AID up-regulation, although the infected cells did not become transformed (Fig. 1 A).


Viral induction of AID is independent of the interferon and the Toll-like receptor signaling pathways but requires NF-kappaB.

Gourzi P, Leonova T, Papavasiliou FN - J. Exp. Med. (2007)

AID up-regulation does not require intact IFN signaling. (A) Mo-MLV infection of mouse bone marrow results in AID upregulation. CD79b expression is a loading control for the RT-PCR reaction. (B) IFN-γ and IFN-αR–deficient bone marrow cells induce AID expression upon viral infection.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2118730&req=5

fig1: AID up-regulation does not require intact IFN signaling. (A) Mo-MLV infection of mouse bone marrow results in AID upregulation. CD79b expression is a loading control for the RT-PCR reaction. (B) IFN-γ and IFN-αR–deficient bone marrow cells induce AID expression upon viral infection.
Mentions: To determine the signaling cascade that induces AID expression in Ab-MLV–infected cells, we first asked whether it required the v-abl kinase, which is the single protein product made by the retrovirus and the cause of transformation. We therefore infected cells with the highly related Moloney murine leukemia virus (Mo-MLV), which does not encode the v-abl kinase. We found that Mo-MLV infection of bone marrow cells resulted in AID up-regulation, although the infected cells did not become transformed (Fig. 1 A).

Bottom Line: Here we show that AID is not an interferon responsive gene and abrogation of Toll-like receptor signaling does not diminish the AID response.However, we found that NF-kappaB was required for expression of virally induced AID.Since NF-kappaB binds and activates the AID promoter, these results mechanistically link viral infection with AID transcription.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Lymphocyte Biology, The Rockefeller University, New York, NY 10021, USA.

ABSTRACT
Activation-induced cytidine deaminase (AID) is expressed in germinal centers of lymphoid organs during immunoglobulin diversification, in bone marrow B cells after infection with Abelson murine leukemia retrovirus (Ab-MLV), and in human B cells after infection by hepatitis C virus. To understand how viruses signal AID induction in the host we asked whether the AID response was abrogated in cells deficient in the interferon pathway or in signaling via the Toll-like receptors. Here we show that AID is not an interferon responsive gene and abrogation of Toll-like receptor signaling does not diminish the AID response. However, we found that NF-kappaB was required for expression of virally induced AID. Since NF-kappaB binds and activates the AID promoter, these results mechanistically link viral infection with AID transcription. Thus, induction of AID by viruses could be the result of several signaling pathways that culminate in NF-kappaB activation, underscoring the versatility of this host defense program.

Show MeSH
Related in: MedlinePlus