Selective inhibition of HIV replication by adriamycin in macrophages but not in lymphocytes.
Adriamycin (ADR) is an anticancer drug commonly used in the treatment of HIV-related cancers. Due to its effect on DNA metabolism, ADR might be able to modulate HIV replication in monocyte-macrophages (M/M), resting cells potentially less sensitive to the toxic effect of this drug. Thus, we assessed the efficacy of ADR against HIV replication in both lymphocytes and M/M. We further investigated the mechanism(s) of action of ADR and its potential synergistic activity with zidovudine (AZT) or alpha-interferon (IFN alpha). ADR consistently inhibited viral replication in M/M: 50% viral inhibition was obtained with 0.005 micrograms/ml ADR, while greater 90% viral inhibition was obtained with 0.05 micrograms/ml ADR. No cell toxicity was seen in M/M at concentrations up to 0.5 micrograms/ml. No anti-HIV activity was shown by ADR in lymphocytes at concentrations up to 0.05 micrograms/ml, that is also the toxic dose 50% (TCID50 for these cells). ADR neither inactivates HIV virions nor affects HIV binding with CD4 receptors. No inhibition of HIV reverse transcriptase by ADR was found at concentrations at least 2,000-fold greater than the 50% HIV inhibitory concentration in M/M. Molecular analysis by polymerase chain reaction (PCR) suggests that ADR substantially affects virus DNA production at concentrations that inhibit viral replication. Finally, late stages of HIV replication were not affected by ADR. At least additive effects of the association ADR + AZT and ADR + IFN alpha were obtained against de novo HIV infection of M/M.(ABSTRACT TRUNCATED AT 250 WORDS)
Bergamini
A
A
Chair of Infectious Diseases, II University of Rome Tor Vergata, Italy.
Perno
C F
CF
Balzarini
J
J
Capozzi
M
M
Marinelli
L
L
Milanese
G
G
Pesce
C D
CD
Calió
R
R
Rocchi
G
G
D000998:Antiviral Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D004317:Doxorubicin / Q000494:pharmacology*; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007700:Kinetics; D008214:Lymphocytes / Q000382:microbiology*; D008264:Macrophages / Q000382:microbiology*; D018894:Reverse Transcriptase Inhibitors; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D018894:Reverse Transcriptase Inhibitors; D004317:Doxorubicin; D054303:HIV Reverse Transcriptase