N-acetyl-cysteine and L-2-oxathiazolidine-4-carboxylic acid enhance contact-dependent growth of HIV in resting peripheral blood mononuclear cells (PBMC) in vitro and increase recovery of HIV from human-PBMC SCID mice

Ping Chen, Gerhard Bauer, James Mitchell, Rachel Factor, Richard Markham, David H. Schwartz

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Objectives: To ascertain the effects of N-acetyl-cysteine (NAC) and L-2-oxothiazolidine-4-carboxylic acid (OTC) on HIV replication in resting T lymphocytes mixed with chronically infected U1 promonocytic cells; examine the phenotypes of NAC- and OTC-treated cells; and monitor HIV recovery from hu-PBMC SCID mice (SCID mice infected with HIV-1(BaL) reconstituted with human peripheral blood mononuclear cells) treated with oral OTC. Design and Methods: Unstimulated PBMC from uninfected donors preincubated for 2 days with pH-adjusted NAC or OTC were cultured at a concentration of 1 x 106 cells/ml with 100 U1 cells that were chronically infected with HIV-1(IIIB). HIV-1 production in the presence or absence of zidovudine was measured by p24 assay at 1-3 weeks, and results were compared with values from the same cell cultures maintained without NAC or OTC exposure. In some experiments U1 cells were separated from PBMC by a ·0.4 μm membrane. NAC-treated and -untreated cells were subjected to FACS analysis of multiple-cell-surface adhesion and activation molecules and the results were compared. Hu-PBMC SCID mice were fed OTC for 3 days prior to infection with HIV-1(BaL) and for the next 3 weeks. Mice were then sacrificed and peritoneal lavage cells were cultured for virus analysis. Results: Unstimulated, non-dividing PBMC supported high levels of HIV replication when in direct contact with U1 cells in the presence of NAC or OTC; CD2 and CD54 (I-CAM1) were down-regulated on NAC-treated PBMC; and OTC-treated mice produced significantly higher yields of HIV-1 from peritoneal cells than did untreated mice. Conclusions: At concentrations ≤ 5 mM, NAC and OTC potentiate HIV growth in unstimulated PBMC in vitro and in SCID mice. Caution in the use of these agents as antiviral monotherapies is advisable.

Original languageEnglish (US)
Pages (from-to)33-41
Number of pages9
JournalAIDS
Volume11
Issue number1
DOIs
StatePublished - 1997
Externally publishedYes

Fingerprint

SCID Mice
Acetylcysteine
Carboxylic Acids
Blood Cells
Cysteine
HIV
HIV-1
Growth
Peritoneal Lavage
4-oxothiazolidine
In Vitro Techniques
Zidovudine
Cell Adhesion
Antiviral Agents
Cultured Cells
Cell Culture Techniques
Viruses
T-Lymphocytes
Phenotype
Membranes

Keywords

  • CD2
  • CD54
  • Contact-dependent activation
  • N-acetyl-cysteine
  • Procysteine
  • Resting peripheral blood mononuclear cells
  • SCID mice

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

N-acetyl-cysteine and L-2-oxathiazolidine-4-carboxylic acid enhance contact-dependent growth of HIV in resting peripheral blood mononuclear cells (PBMC) in vitro and increase recovery of HIV from human-PBMC SCID mice. / Chen, Ping; Bauer, Gerhard; Mitchell, James; Factor, Rachel; Markham, Richard; Schwartz, David H.

In: AIDS, Vol. 11, No. 1, 1997, p. 33-41.

Research output: Contribution to journalArticle

@article{20c56bbf61ff4d8ab06b94f41a67a38e,
title = "N-acetyl-cysteine and L-2-oxathiazolidine-4-carboxylic acid enhance contact-dependent growth of HIV in resting peripheral blood mononuclear cells (PBMC) in vitro and increase recovery of HIV from human-PBMC SCID mice",
abstract = "Objectives: To ascertain the effects of N-acetyl-cysteine (NAC) and L-2-oxothiazolidine-4-carboxylic acid (OTC) on HIV replication in resting T lymphocytes mixed with chronically infected U1 promonocytic cells; examine the phenotypes of NAC- and OTC-treated cells; and monitor HIV recovery from hu-PBMC SCID mice (SCID mice infected with HIV-1(BaL) reconstituted with human peripheral blood mononuclear cells) treated with oral OTC. Design and Methods: Unstimulated PBMC from uninfected donors preincubated for 2 days with pH-adjusted NAC or OTC were cultured at a concentration of 1 x 106 cells/ml with 100 U1 cells that were chronically infected with HIV-1(IIIB). HIV-1 production in the presence or absence of zidovudine was measured by p24 assay at 1-3 weeks, and results were compared with values from the same cell cultures maintained without NAC or OTC exposure. In some experiments U1 cells were separated from PBMC by a ·0.4 μm membrane. NAC-treated and -untreated cells were subjected to FACS analysis of multiple-cell-surface adhesion and activation molecules and the results were compared. Hu-PBMC SCID mice were fed OTC for 3 days prior to infection with HIV-1(BaL) and for the next 3 weeks. Mice were then sacrificed and peritoneal lavage cells were cultured for virus analysis. Results: Unstimulated, non-dividing PBMC supported high levels of HIV replication when in direct contact with U1 cells in the presence of NAC or OTC; CD2 and CD54 (I-CAM1) were down-regulated on NAC-treated PBMC; and OTC-treated mice produced significantly higher yields of HIV-1 from peritoneal cells than did untreated mice. Conclusions: At concentrations ≤ 5 mM, NAC and OTC potentiate HIV growth in unstimulated PBMC in vitro and in SCID mice. Caution in the use of these agents as antiviral monotherapies is advisable.",
keywords = "CD2, CD54, Contact-dependent activation, N-acetyl-cysteine, Procysteine, Resting peripheral blood mononuclear cells, SCID mice",
author = "Ping Chen and Gerhard Bauer and James Mitchell and Rachel Factor and Richard Markham and Schwartz, {David H.}",
year = "1997",
doi = "10.1097/00002030-199701000-00006",
language = "English (US)",
volume = "11",
pages = "33--41",
journal = "AIDS",
issn = "0269-9370",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - N-acetyl-cysteine and L-2-oxathiazolidine-4-carboxylic acid enhance contact-dependent growth of HIV in resting peripheral blood mononuclear cells (PBMC) in vitro and increase recovery of HIV from human-PBMC SCID mice

AU - Chen, Ping

AU - Bauer, Gerhard

AU - Mitchell, James

AU - Factor, Rachel

AU - Markham, Richard

AU - Schwartz, David H.

PY - 1997

Y1 - 1997

N2 - Objectives: To ascertain the effects of N-acetyl-cysteine (NAC) and L-2-oxothiazolidine-4-carboxylic acid (OTC) on HIV replication in resting T lymphocytes mixed with chronically infected U1 promonocytic cells; examine the phenotypes of NAC- and OTC-treated cells; and monitor HIV recovery from hu-PBMC SCID mice (SCID mice infected with HIV-1(BaL) reconstituted with human peripheral blood mononuclear cells) treated with oral OTC. Design and Methods: Unstimulated PBMC from uninfected donors preincubated for 2 days with pH-adjusted NAC or OTC were cultured at a concentration of 1 x 106 cells/ml with 100 U1 cells that were chronically infected with HIV-1(IIIB). HIV-1 production in the presence or absence of zidovudine was measured by p24 assay at 1-3 weeks, and results were compared with values from the same cell cultures maintained without NAC or OTC exposure. In some experiments U1 cells were separated from PBMC by a ·0.4 μm membrane. NAC-treated and -untreated cells were subjected to FACS analysis of multiple-cell-surface adhesion and activation molecules and the results were compared. Hu-PBMC SCID mice were fed OTC for 3 days prior to infection with HIV-1(BaL) and for the next 3 weeks. Mice were then sacrificed and peritoneal lavage cells were cultured for virus analysis. Results: Unstimulated, non-dividing PBMC supported high levels of HIV replication when in direct contact with U1 cells in the presence of NAC or OTC; CD2 and CD54 (I-CAM1) were down-regulated on NAC-treated PBMC; and OTC-treated mice produced significantly higher yields of HIV-1 from peritoneal cells than did untreated mice. Conclusions: At concentrations ≤ 5 mM, NAC and OTC potentiate HIV growth in unstimulated PBMC in vitro and in SCID mice. Caution in the use of these agents as antiviral monotherapies is advisable.

AB - Objectives: To ascertain the effects of N-acetyl-cysteine (NAC) and L-2-oxothiazolidine-4-carboxylic acid (OTC) on HIV replication in resting T lymphocytes mixed with chronically infected U1 promonocytic cells; examine the phenotypes of NAC- and OTC-treated cells; and monitor HIV recovery from hu-PBMC SCID mice (SCID mice infected with HIV-1(BaL) reconstituted with human peripheral blood mononuclear cells) treated with oral OTC. Design and Methods: Unstimulated PBMC from uninfected donors preincubated for 2 days with pH-adjusted NAC or OTC were cultured at a concentration of 1 x 106 cells/ml with 100 U1 cells that were chronically infected with HIV-1(IIIB). HIV-1 production in the presence or absence of zidovudine was measured by p24 assay at 1-3 weeks, and results were compared with values from the same cell cultures maintained without NAC or OTC exposure. In some experiments U1 cells were separated from PBMC by a ·0.4 μm membrane. NAC-treated and -untreated cells were subjected to FACS analysis of multiple-cell-surface adhesion and activation molecules and the results were compared. Hu-PBMC SCID mice were fed OTC for 3 days prior to infection with HIV-1(BaL) and for the next 3 weeks. Mice were then sacrificed and peritoneal lavage cells were cultured for virus analysis. Results: Unstimulated, non-dividing PBMC supported high levels of HIV replication when in direct contact with U1 cells in the presence of NAC or OTC; CD2 and CD54 (I-CAM1) were down-regulated on NAC-treated PBMC; and OTC-treated mice produced significantly higher yields of HIV-1 from peritoneal cells than did untreated mice. Conclusions: At concentrations ≤ 5 mM, NAC and OTC potentiate HIV growth in unstimulated PBMC in vitro and in SCID mice. Caution in the use of these agents as antiviral monotherapies is advisable.

KW - CD2

KW - CD54

KW - Contact-dependent activation

KW - N-acetyl-cysteine

KW - Procysteine

KW - Resting peripheral blood mononuclear cells

KW - SCID mice

UR - http://www.scopus.com/inward/record.url?scp=0031023847&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031023847&partnerID=8YFLogxK

U2 - 10.1097/00002030-199701000-00006

DO - 10.1097/00002030-199701000-00006

M3 - Article

C2 - 9110073

AN - SCOPUS:0031023847

VL - 11

SP - 33

EP - 41

JO - AIDS

JF - AIDS

SN - 0269-9370

IS - 1

ER -