Inhibition of human immunodeficiency virus type 1 replication by hydroxychloroquine in T cells and monocytes.
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.
Sperber
K
K
Division of Clinical Immunology, Mount Sinai Medical Center, New York, NY 10029.
Kalb
T H
TH
Stecher
V J
VJ
Banerjee
R
R
Mayer
L
L
D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D006886:Hydroxychloroquine / Q000494:pharmacology* / Q000633:toxicity; D009000:Monocytes / Q000187:drug effects / Q000382:microbiology*; D012333:RNA, Messenger / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D013601:T-Lymphocytes / Q000187:drug effects / Q000382:microbiology*; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000187:drug effects
D012333:RNA, Messenger; D012367:RNA, Viral; D006886:Hydroxychloroquine