Inhibition of human immunodeficiency virus type 1 replication by hydroxychloroquine in T cells and monocytes

AIDS Res Hum Retroviruses. 1993 Jan;9(1):91-8. doi: 10.1089/aid.1993.9.91.

Abstract

Chloroquine and its analogue hydroxychloroquine (HCQ) have been shown to inhibit a variety of viral infections including influenza and adenovirus through blockade of viral entry via inhibition of endosomal acidification. We have extended these observations to human immunodeficiency virus type 1 (HIV-1) infection utilizing primary T cells and monocytes, a T cell line (CEM), and a monocytic cell line (U-937). HCQ inhibited HIV-1 replication (> 75%), as measured by reverse transcriptase activity, in the primary T cells and monocytes as well as the T cell and monocytic cell lines. HCQ itself had no anti-reverse transcriptase activity and was not toxic to the cells at concentrations inhibitory to viral replication. Intracytoplasmic staining with an anti-p24 antibody, 24 h after infection, revealed the presence of intracytoplasmic virus, suggesting that the drug does not block viral entry. The production of steady-state HIV-1 mRNA was not affected by HCQ in that comparable levels of HIV-1 mRNA could be detected by Northern blot analysis and by in situ hybridization in both the HCQ-treated and untreated cells. However, HCQ does appear to affect production of infectious HIV-1 virions because viral isolates from HCQ-treated cells could not infect target CEM cells. These data suggest that HCQ may be useful adjunctive therapy in the treatment of HIV-1 infection.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • Humans
  • Hydroxychloroquine / pharmacology*
  • Hydroxychloroquine / toxicity
  • Monocytes / drug effects
  • Monocytes / microbiology*
  • RNA, Messenger / genetics
  • RNA, Viral / genetics
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / microbiology*
  • Transcription, Genetic / drug effects
  • Tumor Cells, Cultured
  • Virus Replication / drug effects

Substances

  • RNA, Messenger
  • RNA, Viral
  • Hydroxychloroquine