HIV-1 Persistence and Chronic Induction of Innate Immune Responses in Macrophages

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.

G2-S16 Polyanionic Carbosilane Dendrimer Can Reduce HIV-1 Reservoir Formation by Inhibiting Macrophage Cell to Cell Transmission

“…At 48 h post-treatment, the fluorescence intensity began to diminish, but we still observed a high quantity of G2-S16 dendrimer inside the cells. As reported in the scientific literature, viral particles are able to resist inside macrophages, maintaining the ability to infect new T lymphocytes [24][25][26]. In our results, we observed at 72 h post-treatment that fluorescence intensity decays to low levels but is still observable using confocal microscopy.…”

Toll-Like Receptor (TLR) Signaling Enables Cyclic GMP-AMP Synthase (cGAS) Sensing of HIV-1 Infection in Macrophages

“…Thus, overall, our data are consistent with some of the earlier reports showing that incoming HIV-1 particles are not a strong inducer for a type I IFN response that depends on cGAS sensing of HIV-1 DNA ( 11 , 31 , 42 , 47 , 60 , 84 – 86 ). It should be noted, however, that the early phase is not the only period during which HIV-1 can be sensed, as multiple lines of evidence point to innate immune responses that are elicited by late events of the viral replication cycle ( 13 , 15 , 32 , 33 , 35 , 51 , 87 , 88 ).…”

N6-methyladenosine modification of HIV-1 RNA suppresses type-I interferon induction in differentiated monocytic cells and primary macrophages

“…Myeloid cells, including the monocyte precursors and their differentiated macrophages and dendritic cells, are among the first targets during HIV-1 infection and transmission [32][33][34]. Myeloid cells are important for viral pathogen sensing and inflammation caused by HIV-1 infection [35,36]. A recent study showed that 2 0 -O-methylation in HIV-1 RNA prevents MDA5-mediated sensing in monocytic cell lines, primary macrophages and dendritic cells, thereby reducing IFN-I induction and innate immune responses to HIV-1 [37].…”