Ability of anti-HIV agents to inhibit HIV replication in monocyte/macrophages or U937 monocytoid cells under conditions of enhancement by GM-CSF or anti-HIV antibody.
Monocyte/macrophages (M/M) are an important target cell for human immunodeficiency virus (HIV) infection in the body. The study of HIV infection in these cells, however, is rather complicated because they represent a variable population, and because HIV entry and replication in M/M may be markedly influenced by a number of factors. These must be considered in therapeutic approaches to HIV infection. In the present set of experiments, we studied the interaction between certain agents which increase the infection of monocyte/macrophages (M/M) by HIV and two groups of anti-HIV agents: dideoxynucleosides and specific inhibitors of gp120-CD4 binding. We found that the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF), which markedly enhances HIV replication in M/M, does not affect the activity of recombinant soluble CD4 (sCD4) or OKT4A, two agents which block gp120-CD4 binding. However, it had varying effects on different dideoxynucleosides: GM-CSF increased the net anti-HIV activity of 3'-azido2',3'-dideoxythymidine (AZT), while at the same time it reduced the activity of 2',3'-dideoxycytidine (ddC) and 2',3'-dideoxyinosine (ddI). These effects probably represent an interplay between varying effects of GM-CSF on drug entry and phosphorylation. In additional experiments, we showed that very low concentrations of anti-HIV antibodies could enhance HIV infection of the U937 monocytoid cell line. Interestingly, while this effect has been hypothesized to occur through a CD4-independent mechanism, we found that the anti-HIV activities of both sCD4 and OKT4A were unchanged under conditions of enhancement.(ABSTRACT TRUNCATED AT 250 WORDS)
Perno
C F
CF
National Cancer Institute, Bethesda, MD 20892.
Cooney
D A
DA
Currens
M J
MJ
Rocchi
G
G
Johns
D G
DG
Broder
S
S
Yarchoan
R
R
D000998:Antiviral Agents / Q000494:pharmacology*; D015704:CD4 Antigens / Q000378:metabolism; D002460:Cell Line; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006678:HIV / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology; D015483:HIV Antibodies / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000382:microbiology*; D009000:Monocytes / Q000187:drug effects / Q000382:microbiology*; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D015704:CD4 Antigens; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D016178:Granulocyte-Macrophage Colony-Stimulating Factor