Morphine-induced transactivation of HIV-1 LTR in human neuroblastoma cells.
Infection by human immunodeficiency virus (HIV) is followed in many cases by a clinically quiescent or latent phase that appears to continue as long as host antiviral defense is intact. This has raised the possibility that certain host susceptibility factors (i.e., environmental cofactors) might influence the progression of the disease. In this study we demonstrate that morphine can function to activate HIV/LTR-CAT fusion gene (HIV-long terminal repeat-chloramphenicol acetyltransferase) when transfected into undifferentiated human SH-SY5Y neuroblastoma cells. The stimulatory effect of morphine is amplified in SH-SY5Y cells that have been induced to differentiate first with phorbol 12-myristate 13-acetate (PMA) and is much less in cells differentiated with retinoic acid (RA). Morphine does not appreciably activate HIV/LTR-CAT expression in human MOLT-3 and other T cells. Morphine activation of HIV/LTR-CAT in the SH-SY5Y cells is not reversible by naltrexone and appears to involve a Fos/Jun signaling system. Our results suggest that narcotics such as morphine may lead to activation of latent HIV infection. This may be particularly important in tissues, such as brain, which can host latent HIV infection and which is uniquely damaged in patients with acquired immunodeficiency syndrome (AIDS) as evidenced by neuronal degeneration and dementia. We also predict that these findings may have important implications for the pathogenesis of AIDS, particularly in opiate drug abusers.
Squinto
S P
SP
Department of Biochemistry, LSU Medical Center, New Orleans 70119.
Mondal
D
D
Block
A L
AL
Prakash
O
O
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D016325:HIV Long Terminal Repeat / Q000187:drug effects*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D009020:Morphine / Q000494:pharmacology*; D009447:Neuroblastoma / Q000382:microbiology; D019966:Substance-Related Disorders / Q000150:complications; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000382:microbiology
D009020:Morphine