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PMID: 1700829 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Increased human immunodeficiency virus (HIV) expression in chronically infected U937 cells upon in vitro differentiation by hydroxyvitamin D3: roles of interferon and tumor necrosis factor in regulation of HIV production.

Journal of virology ·Vol. 64 ·No. 12 ·1990-12-00 ·Pages 5874-82

Locardi C, Petrini C, Boccoli G, Testa U, Dieffenbach C, Buttò S, Belardelli F

Abstract

We have investigated the roles of cytokines in the modulation of human immunodeficiency virus (HIV) production in chronically infected U937 cells upon in vitro differentiation by hydroxyvitamin D3. HIV-infected U937 cells exhibited markedly lower levels of CD4 and HLA-DR antigens than uninfected cells did. Vitamin D3 induced a time-dependent macrophagelike differentiation, as determined by monitoring the expression of some surface antigens by means of the monoclonal antibodies OKM1, OKM5, OKM13, OKM14, OKT4, anti-HLA-DR, TecMG2, TecMG3, LeuM3, LeuM1, anti-HLA-DP, and anti-HLA-DQ. Treatment with hydroxyvitamin D3 resulted in a marked increase in HIV production compared with control cultures. Interleukin 1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha) were detected in the culture media, whereas interferon (IFN) was not generally found. Using the polymerase chain reaction technique, we found HIV-infected U937 cells to express detectable levels of mRNAs for alpha interferon (IFN-alpha), IFN-beta, TNF-alpha, and IL-1 beta. The addition of TNF resulted in a marked increase of HIV production, whereas IL-1 beta was ineffective. In contrast, both IFN-alpha and IFN-beta exerted some inhibitory effect on HIV production, which was more marked in vitamin D3-treated cultures than in untreated cultures. HIV production was significantly increased by antibodies to IFN-alpha in both untreated and vitamin D3-treated cultures. Anti-IFN-beta antibody increased HIV production only in vitamin D3-treated cells. In contrast, anti-TNF-alpha antibodies markedly decreased HIV production in both control and differentiating U937 cells. Vitamin D3 treatment resulted in a higher expression of TNF receptors in differentiating cells than in control HIV-infected cells. These data demonstrate a strong correlation between HIV production and macrophagelike differentiation in chronically infected U937 cells and suggest that endogenous IFN and TNF exert opposite effects in the regulation of virus production in both undifferentiated and vitamin D3-treated cell cultures.

MeSH Terms
Antibodies, Monoclonal Antigens, CD/analysis Antigens, Surface/analysis Base Sequence CD4 Antigens/analysis Calcifediol/pharmacology Cell Differentiation/drug effects Cell Line Cytokines/pharmacology HIV/drug effects,genetics,physiology HLA Antigens/analysis Humans Interferon Type I/pharmacology Interleukin-1/pharmacology Kinetics Lymphoma, Large B-Cell, Diffuse Molecular Sequence Data RNA-Directed DNA Polymerase/analysis Receptors, Cell Surface/biosynthesis,drug effects,physiology Receptors, Tumor Necrosis Factor Recombinant Proteins/pharmacology Tumor Necrosis Factor-alpha/metabolism,pharmacology Virus Replication/drug effects
Chemicals
Antibodies, Monoclonal Antigens, CD Antigens, Surface CD4 Antigens Cytokines HLA Antigens Interferon Type I Interleukin-1 Receptors, Cell Surface Receptors, Tumor Necrosis Factor Recombinant Proteins Tumor Necrosis Factor-alpha RNA-Directed DNA Polymerase Calcifediol
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Locardi C
Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy.
Petrini C
Boccoli G
Testa U
Dieffenbach C
Buttò S
Belardelli F
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.64.12.5874-5882.1990
Published
1990-12-00
Pages
5874-82
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC248750
Subset
IM
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1128/JVI.64.12.5874-5882.1990 PMC Full Text View journal details
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