Megalomicin inhibits HIV-1 replication and interferes with gp160 processing.
The inhibitory effects on HIV replication of megalomicin (MGM, an inhibitor of intra-Golgi vesicle transport, have been studied. In experiments at low multiplicity of infection on Jurkat and MT2 cell lines. MGM inhibited the production of p24 antigen, the formation of syncytia, and the induction of apoptosis at concentrations below 5 microM. Furthermore, PCR analysis of genomic DNA showed that, in the presence of MGM, HIV-1 had been eradicated from the culture. MGM also inhibited replication of primary isolates of HIV-1 in blood lymphoblasts and more importantly, at 1 microM, MGM inhibited depletion of CD4+ T cells in cultures of blood lymphocytes from seropositive patients. Finally, MGM inhibited the generation of infectious virions and the processing of the envelope protein precursor gp160 to its mature forms, resulting in the rapid degradation of gp 160. These data suggest that MGM induces a powerful inhibitory effect on HIV-1 replication at nontoxic concentrations by preventing the processing of HIV-1 gp160 envelope protein and the subsequent formation of infectious viral particles.
San José
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Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Universidad Autónoma de Madrid, Spain.
Muñoz-Fernández
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Alarcón
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D000900:Anti-Bacterial Agents; D019380:Anti-HIV Agents / Q000494:pharmacology*; D017209:Apoptosis; D001692:Biological Transport / Q000187:drug effects; D015704:CD4 Antigens / Q000096:biosynthesis / Q000235:genetics; D018791:CD4 Lymphocyte Count / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002461:Cell Line, Transformed; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D006056:Golgi Apparatus / Q000378:metabolism; D019302:HIV Envelope Protein gp160 / Q000378:metabolism*; D006679:HIV Seropositivity / Q000097:blood; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006367:HeLa Cells; D015368:Human T-lymphotropic virus 1; D006801:Humans; D019169:Jurkat Cells / Q000821:virology; D018942:Macrolides / Q000494:pharmacology; D008561:Membrane Fusion / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014779:Virus Replication / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D019380:Anti-HIV Agents; D015704:CD4 Antigens; D019302:HIV Envelope Protein gp160; D018942:Macrolides; D011993:Recombinant Fusion Proteins; C055728:megalomycin C