04 Ago Reversible HIV-1 Latency driven by M1 Polarization of Primary Human Monocyte-Derived Macrophages

Macrophages are present in all tissues and organs and represent primary targets of HIV-1 infection together with CD4+ T lymphocytes. Unlike CD4+ T cells, however, human macrophages are resistant to the cytopathic effects induced by virus infection both in vitro and in vivo. This observation, together with the capacity of macrophages of accumulating virions in virus-containing compartments partially resistant to antiretroviral agents, supports the hypothesis of their role as long-lasting viral reservoirs. Our Laboratory has previously demonstrated that M1 polarization of primary human monocyte-derived macrophage (MDM) with pro-inflammatory cytokines (IFN- and TNF-) leads to a restriction of HIV-1 replication in comparison to unpolarized MDM. With the aim of better understand the role of M1 polarization in containing virus replication, I have restimulate M1-MDM 7 days after infection with the same M1 cytokines (M12 protocol). M12-MDM showed a strengthened capacity to contain virus replication, together with a significant reduction of HIV DNA and a virtual lack of viral RNA in comparison to unpolarized-MDM and to M1-MDM that were not restimulated. Latently infected M12-MDM harbored replication-competent proviruses that was reactivated by coculture with allogeneic PHA-stimulated PBMC or by incubation with their culture supernatant. These findings support the hypothesis that M12 polarization may represent a potential model of in vitro reversible HIV-1 latency in primary MDM.