Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 733-739 |
| Number of pages | 7 |
| Journal | AIDS |
| Volume | 8 |
| Issue number | 6 |
| State | Published - Jun 1 1994 |
| Externally published | Yes |
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Keywords
- B-cell differentiation
- Interleukin-6
- Nef
- T-B-cell contact
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
Cite this
Nef protein of HIV-1 has B-cell stimulatory activity. / Chirmule, Narendra; Oyaizu, Naoki; Saxinger, Carl; Pahwa, Savita G.
In: AIDS, Vol. 8, No. 6, 01.06.1994, p. 733-739.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Nef protein of HIV-1 has B-cell stimulatory activity
AU - Chirmule, Narendra
AU - Oyaizu, Naoki
AU - Saxinger, Carl
AU - Pahwa, Savita G
PY - 1994/6/1
Y1 - 1994/6/1
N2 - 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.
AB - 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.
KW - B-cell differentiation
KW - Interleukin-6
KW - Nef
KW - T-B-cell contact
UR - http://www.scopus.com/inward/record.url?scp=0028298767&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0028298767&partnerID=8YFLogxK
M3 - Article
VL - 8
SP - 733
EP - 739
JO - AIDS
JF - AIDS
SN - 0269-9370
IS - 6
ER -