Anti-rheumatic compound aurothioglucose inhibits tumor necrosis factor-alpha-induced HIV-1 replication in latently infected OM10.1 and Ach2 cells

NF-kappa B is a potent cellular activator of HIV-1 gene expression. Down-re gulation of NF-kappa B activation is known to inhibit HIV replication from the latently Infected cells. Gold compounds have been effectively used for many decades in the treatment of rheumatoid arthritis. We previously report ed that gold compounds, especially aurothioglucose (AuTG) containing monova lent gold ion, inhibited the DNA-binding of NF-kappa B in vitro. In this re port we have examined the efficacy of the gold compound AuTG as an inhibito r of HIV replication in latently infected OM10.1 and Ach2 cells. Tumor necr osis factor (TNF)-alpha-induced HIV-1 replication in OM10.1 or Ach2 cells w as significantly inhibited by non-cytotoxic doses of AuTG (>10 mu M in OM10 .1 cells and >25 mu M in Ach2 cells), while 25 mu M of the counter-anion th ioglucose (TG) or gold compound containing divalent gold ion, HAuCl3, had n o effect. The effect of AuTG on NF-kappa B-dependent gene expression was co nfirmed by a transient CAT assay. Specific staining as well as electron mic roscopic examinations revealed the accumulation of metal gold in the cells, supporting our previous hypothesis that gold ions could block NF-kappa B-D NA binding by a redox mechanism. These observations indicate that the monov alent gold compound AuTG is a potentially useful drug for the treatment of patients infected with HIV.