Nef protein of HIV-1 has B-cell stimulatory activity.
OBJECTIVE
To examine the B-cell stimulatory properties of the regulatory Nef protein of HIV-1.


METHODS
The 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).


RESULTS
A 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.


CONCLUSIONS
These 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.
Chirmule
N
N
Department of Pediatrics, North Shore University Hospital-Cornell University Medical College, Manhasset, New York 11030.
Oyaizu
N
N
Saxinger
C
C
Pahwa
S
S
D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D015693:Gene Products, nef / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008211:Lymphocyte Cooperation; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D054311:nef Gene Products, Human Immunodeficiency Virus
D015693:Gene Products, nef; D015850:Interleukin-6; D012333:RNA, Messenger; D011994:Recombinant Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus