Expression of human immunodeficiency virus long terminal repeat in the human promonocyte cell line U937: effect of endotoxin and cytokines.
Phagocytic macrophages are known to support noncytopathic, chronic infections of human immunodeficiency virus (HIV). Regulation of viral replication in such cells with either chronic low-grade or latent HIV infection is probably influenced by both viral and cellular factors acting on the viral long terminal repeat (LTR). This study identifies naturally occurring biological response modifiers which are able to affect the HIV-LTR linked to the chloramphenicol acetyl transferase (LTR-CAT) gene in a stable transfection of the human promonocyte cell line, U937, in the absence of other viral proteins. In this model system, endotoxin lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha) are able to independently stimulate expression of LTR-CAT. Granulocyte/macrophage-colony-stimulating factor can enhance the effect of TNF-alpha or LPS, but other cytokines tested had minimal or no effect on LTR-CAT. In addition to effects on cellular susceptibility and immune function, the ability of naturally occurring factors to affect HIV-LTR in its integrated state may have particular relevance to progression of active disease from latent infection.
Laboratory of Molecular Immunobiology, National Cancer Institute, Frederick Cancer Research Facility, Maryland 21701.
P S
PS
Latham
A M
AM
Lewis
L
L
Varesio
G N
GN
Pavlakis
B K
BK
Felber
F W
FW
Ruscetti
H A
HA
Young
D001685:Biological Factors / Q000494:pharmacology*; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D016207:Cytokines; D004731:Endotoxins / Q000494:pharmacology*; D006678:HIV / Q000235:genetics*; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D012367:RNA, Viral / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D001685:Biological Factors; D016207:Cytokines; D004731:Endotoxins; D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha; D015500:Chloramphenicol O-Acetyltransferase