While the existence of latently infected CD4+ T cells has been demonstrated in infected individuals receiving cART, whether primary myeloid cells are latently infected remains to be firmly established. In this regard, we have previously reported that short-term exposure of primary MDM established from seronegative individuals to pro-inflammatory cytokines (TNF-a plus IFN-g), a modality of cell activation also known as “M1 polarization,” partially prevented productive virus infection in virtue of a downregulation of CD4 from the cell surface couple with an upregulated secretion of CCR5-binding chemokines (E. Cassol, et al. J Immunol 2009). We have further demonstrated that M1-MDM display a post-entry restriction to productive HIV-1 replication in terms of delayed proviral integration and reduced transcription also when cells were infected with a VSV-g pseudotyped virus bypassing CD4 and CCR5 for viral entry (L. Cassetta, et al. AIDS 2013). We have recently investigated the potential effect of a second M1 polarization of previously infected M1-MDM (M1x2 protocol) and observed a further reduction of virus production to undetectable levels, at least in terms of RT activity in culture supernatants collected for several days post-stimulation. Recovery of virus replication was however achieved by cocultivation of M1x2-infected MDM with allogeneic PHA-stimulated PBMC, suggesting the existence of a pool of MDM latently infected with replication-competent virus. Additional experiments are ongoing to define the time-dependence and different stimulatory conditions of modulation of this state of potential latent infection in primary MDM.
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