Induction of developmentally programmed cell death and activation of HIV by sodium butyrate.
Apoptosis is an important regulatory process during normal development and maturation. We find that the proliferation-arresting and differentiation-inducing compound sodium n-butyrate (NaB) triggers a marked host chromatin degradation. This apoptotic process is independent of, but commensurate with, a rapid increase in viral mRNA synthesis and subsequent release of HIV-1 virus in transformed human cell lines harboring tat- (HLM1) or tat+ (U1, ACH-2) dormant HIV-1 proviruses. This compound stimulates a reversible accumulation of the characteristic viral mRNAs at a much faster rate than two other DNA degradation inducers such as tumor necrosis factor-alpha and phorbol 12-myristate 13-acetate. The transcriptional activator butyrate analogue, alpha-amino-n-butyrate, failed to cause similar phenotypic changes. These results suggest that common regulatory signals may be involved in activation of apoptosis genes and latent provirus by NaB.
Sadaie
M R
MR
Division of Transfusion Transmitted Diseases, Food and Drug Administration, Rockville, Maryland 20852.
Hager
G L
GL
D017209:Apoptosis; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002460:Cell Line; D002843:Chromatin / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D007700:Kinetics; D012367:RNA, Viral / Q000096:biosynthesis; D014775:Virus Activation / Q000187:drug effects
D002087:Butyrates; D002843:Chromatin; D012367:RNA, Viral; D020148:Butyric Acid