Nef protein of HIV‐1 has B‐cell stimulatory activity
作者:
Narendra Chirmule,
Naoki Oyaizu,
Carl Saxinger,
Savita Pahwa,
期刊:
AIDS
(OVID Available online 1994)
卷期:
Volume 8,
issue 6
页码: 733-740
ISSN:0269-9370
年代: 1994
出版商: OVID
关键词: Nef;interleukin-6;B-cell differentiation;T-B-cell contact
数据来源: OVID
摘要:
ObjectiveTo examine the B-cell stimulatory properties of the regulatory Nef protein of HIV-1.MethodsThe effect of the HIV-1 regulatory proteins Nef, Tat and Vif, were analyzed for their ability to induce differentiation of normal B lymphocytes into immunoglobulin secreting cells (ISC).ResultsA recombinant Nef protein, but neither Tat or Vif, was able to induce ISC in peripheral blood lymphocyte (PBL) cultures of HIV-1-seronegative donors. Another recombinant Nef protein, d-Nef, with a truncated amino terminal (deletion of 34 amino acids) failed to induce B-cell differentiation. Pretreatment of the Nef protein with a polyclonal anti-Nef-antibody abrogated its B-cell stimulatory activity. The Nef-induced B-cell differentiation was dependent on cell-to-cell contact. Cell surface molecules leukocyte function-associated molecule (LFA)-1, intracellular adhesion molecule (ICAM)-1, human lymphocyte antigen-DR and B7 were involved in the T-B-cell interaction because monoclonal antibodies to these molecules abrogated the Nef-induced B-cell differentiation response. The Nef protein was able to induce interleukin (IL)-6 messenger (m)RNA and IL-6 protein secretion in PBL, with monocytes as the primary source.ConclusionsThese findings indicate that regulatory (Nef) proteins of HIV-1 contribute to the intense B-cell activation that occurs in association with HIV-1 infection. T-B-cell contact-dependent interaction and induction of IL-6 by these proteins appear to play major roles in this process.
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