-- HIV-1 Nef protein, by inducing resistance to macrophage-tropic HIV infection in monocyte-derived macrophages (MDMs), triggers the shift to T-cell-tropic infection portending progression to full-blown AIDS, virologists report.
"Increasing interest has been devoted to the role that monocyte-macrophages play in the pathogenesis of AIDS," explained M. Federico and colleagues at the Istituto Superiore di Sanita in Rome. "The hypothesis of an involvement in AIDS pathogenesis of human/simian immunodeficiency virus (HIV/SIV) Nef also is currently under evaluation by many investigators." This is based on "evidence that monkeys infected with a nef-deleted SIV strain failed to develop simian AIDS," they added.
Writing in the Journal of General Virology, Federico et al. described their study, which evaluated the results of exposing MDMs to recombinant HIV-1 Nef protein (rNef) ("T-tropic human immunodeficiency virus (HIV) type 1 Nef protein enters human monocyte-macrophages and induces resistance to HIV replication: A possible mechanism of HIV T-tropic emergence in AIDS," J Gen Virol 2000 Dec;81 Pt 12:2905-17).
They found that MDMs treated with rNef displayed a rapid downregulation of the CD4 HIV receptor, suggesting that rNef blocked macrophage-tropic HIV infection at the viral entry level. The fact that CD4-independent infection was not at all affected by the presence or absence of rNef exposure reinforced this conclusion, the researchers noted.
However, although rNef exposure made MDMs more resistant to macrophage-tropic HIV infection, the net effect was ultimately to give the more virulent T cell-tropic HIV strains a competitive advantage, study data showed.
"We propose that extracellular Nef contributes to AIDS pathogenesis by inducing resistance to M-tropic HIV replication in MDM, thereby facilitating the switching from M- to T-tropic HIV prevalence that correlates frequently with AIDS progression," Federico and colleagues concluded.
The contact person for this report is M. Federico, Istituto Superiore di Sanita, Virology Lab, Viale Regina Elena 299, I-0061 Rome, Italy.
Key points reported in this study include:
- HIV-1 Nef protein can trigger the shift to T-cell-tropic infection portending progression to full-blown AIDS
- Exposing MDMs to recombinant Nef protein resulted in a downregulation of the CD4 HIV receptor, blocking macrophage-tropic HIV infection
- However, the net result of this change was to give the more virulent T-cell-tropic HIV strains a competitive advantage
This article was prepared by AIDS Weekly editors from staff and other reports.