The Interplay of HIV-1 and Macrophages in Viral Persistence

Abstract

HIV-1 has evolved mechanisms to evade host cell immune responses and persist for lifelong infection. Latent cellular reservoirs are responsible for this persistence of HIV-1 despite the powerful effects of highly active antiretroviral therapies (HAART) to control circulating viral load. While cellular reservoirs have been extensively studied, much of these studies have focused on peripheral blood and resting memory CD4+ T cells containing latent HIV-1 provirus; however, efforts to eradicate cellular reservoirs have been stunted by reservoirs found in tissues compartments that are not easily accessible. These tissues contain resting memory CD4+ T cells and tissue resident macrophages, another latent cellular reservoir to HIV-1. Tissue resident macrophages have been associated with HIV-1 infection since the 1980s, and evidence has continued to grow regarding their role in HIV-1 persistence. Specific biological characteristics play a vital role as to why macrophages are latent cellular reservoirs for HIV-1, and in vitro and in vivo studies exhibit how macrophages contribute to viral persistence in individuals and animals on antiretroviral therapies. In this review, we characterize the role and evolutionary advantages of macrophage reservoirs to HIV-1 and their contribution to HIV-1 persistence. In acknowledging the interplay of HIV-1 and macrophages in the host, we identify reasons why current strategies are incapable of eliminating HIV-1 reservoirs and why efforts must focus on eradicating reservoirs to find a future functional cure.

Neurological complications during HIV infection

“…Fortunately, due to the advent of ART, which is able to reduce the viral load to undetectable levels, AIDS-associated morbidity and mortality have significantly dropped. However, HIV is able to seed reservoirs early in infection, allowing the viral load to rebound after treatment interruption [14][15][16]. Thus, HIV infection is nowadays a chronic disease with the need for constant therapy to maintain clinical stability and low viral loads.…”

Editorial: Direct and Indirect Interactions of HIV With Host Cells

“…Direct and Indirect Interactions of HIV With Host Cells HIV causes AIDS by infection and depletion of CD4 + T cells. HIV can also infect other CD4 + cells such as macrophages, possibly leading to their functional alterations and contribution to viral reservoirs (Hendricks et al, 2021). HIV infection may also result in changes in other hematopoietic cells such as hematopoietic stem/progenitor cells (HSPCs), CD8 + T cells, B cells, natural killer cells, dendritic cells (DCs), and granulocytes (Virgilio and Collins, 2020;Dillon and Wilson, 2021;Madzime et al, 2021).…”

HIV-1 cell-to-cell spread overcomes the virus entry block of non-macrophage-tropic strains in macrophages

“…Together with latently-infected CD4 T cells, they also act as cellular reservoirs for the virus, which represent a major obstacle to its eradication and can contribute to persistence of adverse effects in infected patients despite effective antiretroviral therapy [9][10][11]. For instance, residual infection of perivascular MΦ and microglial cells in the CNS is estimated to be the cause of chronic brain inflammation and neurocognitive disorders experienced by half of the patients under therapy [12].…”