Abstract
A hallmark of HIV-1 infection is chronic inflammation, which plays a significant role in disease pathogenesis. Acute HIV infection induces robust inflammatory responses, which are insufficient to prevent or eliminate virus in mucosal tissues. While establishment of viral set-point is coincident with downregulation of acute innate responses, systemic inflammatory responses persist during the course of chronic HIV infection. Since the introduction of combination antiviral therapy (cART), most HIV-1+ individuals can suppress viremia under detection levels for decades. However, chronic immune activation persists and has been postulated to cause HIV associated non-AIDS complications (HANA). Importantly, inflammatory cytokines and activation markers associated with macrophages are strongly and selectively correlated with the incidence of HIV-associated neurocognitive disorder (HAND), cardiovascular dysfunctions (CVD) and other HANA conditions. In this review, we discuss the roles of macrophages in facilitating viral persistence and contributing to generation of persistent inflammatory responses.
Highlights
A hallmark of HIV-1 infection is chronic inflammation, which plays a significant role in disease pathogenesis
Recent findings have demonstrated that sequences of HIV-1 recovered from latently-infected resting
CD4+ T cells in blood by in vitro stimulation are frequently different from those of rebound HIV-1 upon interruption of combination antiviral therapy (cART) or latency reversing agent treatment [154,155,156]. These findings suggest the importance of studying HIV reservoirs in tissues
Summary
Tissue-resident macrophages such as those in the lungs (alveolar macrophages), the central nervous system (CNS, microglia), the bones (osteoclasts) and the spleen (splenic macrophages). A recent study in humanized mouse model of HIV-1 infection utilized electron tomography to reveal the presence of budding virions from infected bone-marrow resident macrophages [9] In contrast to these studies, the role of macrophage infection in vivo has been challenged by the findings that transmitted/founder (T/F) viruses are unable to efficiently infect monocyte-derived macrophages (MDMs) [10,11,12,13]. Infection of MoM with HIV has resulted in persistent infection of human macrophages and, importantly, rebound of viremia after interruption of cART [25] These studies suggest that while the route of infection and extent of virus production from infected macrophages would vary depending on anatomical locations and course of infection, tissue-resident macrophages contribute to HIV replication and persistence in vivo
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