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

C. F. Perno, D. A. Cooney, M. J. Currens, G. Rocchi, D. G. Johns, S. Broder, R. Yarchoan

Research output: Contribution to journalArticle

Abstract

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'-dideoxythinosine (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. This suggests that even with enhancing antibodies, CD4 binding may be an essential step in viral entry. Also, this observation suggests that agents such as sCD4 might be effective clinically in M/M even if enhancing antibodies are present. Taken together, the results indicate that stimuli which enhance HIV replication in M/M may have a variety of effects on potential anti-HIV agents, and that such interactions should be considered in formulating antiretroviral strategies in AIDS.

Original languageEnglish
Pages (from-to)1051-1055
Number of pages5
JournalAIDS Research and Human Retroviruses
Volume6
Issue number8
Publication statusPublished - 1990

ASJC Scopus subject areas

  • Immunology
  • Virology

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