We read with interest the recent article by Cui et al. (1) in which they show that HIV-1 infection of monocyte-derived macrophages (MDM) induces dephosphorylation and nuclear translocation of the proapoptotic transcription factor FOXO3a. This extends their previous work showing that TRAIL-mediated apoptosis of HIV-infected MDM is dependent on phosphorylation of Akt-1 upstream of FOXO3a (2). However, their interpretation in the present report suggests that HIV-1 infection directly induces apoptosis of macrophages. This misrepresents an extensive body of literature that finds no direct cytopathic effect of HIV infection in MDM (3) and indeed their own earlier results in which apoptosis is induced only after stimulation with recombinant human TRAIL (2). We are also engaged in study of HIV-1 infection in MDM and find no evidence on the basis of cell viability or genomic transcriptional profiling for direct induction of apoptosis or necrosis (see Fig. 1). The significance of this is that HIV-1 can establish a reservoir of infection in long-lived cells that may contribute to viral persistence. The possibility that HIV-1 infection can prime MDM for apoptosis is of significant interest but should be placed in context with evidence that HIV-1 may protect macrophages from apoptosis (4, 5) and that HIV-infected macrophages can induce apoptosis of bystander cells contributing to T cell or neuronal death (6, 7).
Comment on “Transcription Factor FOXO3a Mediates Apoptosis in HIV-1-Infected Macrophages”
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Mahdad Noursadeghi, Jhen Tsang, Robert F. Miller, David R. Katz; Comment on “Transcription Factor FOXO3a Mediates Apoptosis in HIV-1-Infected Macrophages”. J Immunol 15 June 2008; 180 (12): 7783. https://doi.org/10.4049/jimmunol.180.12.7783
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