Title | Human immunodeficiency virus 1 Nef suppresses CD40-dependent immunoglobulin class switching in bystander B cells. |
Publication Type | Journal Article |
Year of Publication | 2006 |
Authors | Qiao X, He B, Chiu A, Knowles DM, Chadburn A, Cerutti A |
Journal | Nat Immunol |
Volume | 7 |
Issue | 3 |
Pagination | 302-10 |
Date Published | 2006 Mar |
ISSN | 1529-2908 |
Keywords | B-Lymphocytes, Bystander Effect, CD40 Antigens, CD40 Ligand, Cells, Cultured, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Gene Products, nef, HIV-1, Humans, I-kappa B Kinase, Immunoblotting, Immunoglobulin Class Switching, Immunohistochemistry, Microscopy, Confocal, nef Gene Products, Human Immunodeficiency Virus, NF-kappa B, Reverse Transcriptase Polymerase Chain Reaction, STAT Transcription Factors, Suppressor of Cytokine Signaling Proteins, T-Lymphocytes |
Abstract | 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 IkappaB 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 IkappaBalpha and SOCS proteins, which blocked CD154 and cytokine signaling via NF-kappaB 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. |
DOI | 10.1038/ni1302 |
Alternate Journal | Nat Immunol |
PubMed ID | 16429138 |
Grant List | R01 AR047872 / AR / NIAMS NIH HHS / United States R21 AI057130 / AI / NIAID NIH HHS / United States R01 AI057653 / AI / NIAID NIH HHS / United States AI057653 / AI / NIAID NIH HHS / United States AI057530 / AI / NIAID NIH HHS / United States R01 AI074378 / AI / NIAID NIH HHS / United States |
Related Faculty:
Amy Chadburn, M.D.