Journal
NATURE IMMUNOLOGY
Volume 7, Issue 3, Pages 302-310Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni1302
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Funding
- NIAID NIH HHS [R01 AI074378, R21 AI057130, R01 AI057653, AI057653, AI057530] Funding Source: Medline
- NIAMS NIH HHS [R01 AR047872] Funding Source: Medline
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Immunoglobulin class switching from immunoglobulin M (IgM) to IgG and IgA is central to immunity against viruses and requires the activation of B cells by T cells via CD154 (CD40 ligand) and cytokines. These molecules limit their signaling activity in immune cells by turning on negative feedback proteins, including I kappa B and SOCS. We show here that negative factor (Nef) protein, an immunosuppressive human immunodeficiency virus 1 protein expressed and released by infected cells, penetrates B cells both in vivo and in vitro. Nef suppressed immunoglobulin class-switch DNA recombination by inducing I kappa B alpha and SOCS proteins, which blocked CD154 and cytokine signaling via NF-kappa B and STAT transcription factors. Thus, human immunodeficiency virus 1 may evade protective T cell-dependent IgG and IgA responses by 'hijacking' physiological feedback inhibitors in B cells via Nef.
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