HIV-1 Latency in Monocytes/Macrophages

Abstract

Human immunodeficiency virus type 1 (HIV-1) targets CD4+ T cells and cells of the monocyte/macrophage lineage. HIV pathogenesis is characterized by the depletion of T lymphocytes and by the presence of a population of cells in which latency has been established called the HIV-1 reservoir. Highly active antiretroviral therapy (HAART) has significantly improved the life of HIV-1 infected patients. However, complete eradication of HIV-1 from infected individuals is not possible without targeting latent sources of infection. HIV-1 establishes latent infection in resting CD4+ T cells and findings indicate that latency can also be established in the cells of monocyte/macrophage lineage. Monocyte/macrophage lineage includes among others, monocytes, macrophages and brain resident macrophages. These cells are relatively more resistant to apoptosis induced by HIV-1, thus are important stable hideouts of the virus. Much effort has been made in the direction of eliminating HIV-1 resting CD4+ T-cell reservoirs. However, it is impossible to achieve a cure for HIV-1 without considering these neglected latent reservoirs, the cells of monocyte/macrophage lineage. In this review we will describe our current understanding of the mechanism of latency in monocyte/macrophage lineage and how such cells can be specifically eliminated from the infected host.

Use of the CRISPR/Cas9 system as an intracellular defense against HIV-1 infection in human cells

“…To test whether the CRISPR/Cas9 system could confer HIV-1 resistance to haematopoietic lineages that could serve as latent HIV reservoirs, such as monocyte/macrophage lineages 26 , several piggyBac-mediated anti-HIV-1 hPSC lines were generated and confirmed for Cas9 protein expression by western blotting (Fig. 4d).…”

“…4a-j). Meanwhile, the CRISPR/Cas9 system has been applied to target other infective viruses, such as papillomavirus, type I herpes simplex virus and hepatitis B virus by other groups 26,29,30 . These results demonstrated the generality of the CRISPR/Cas9 system for application as either a viral genome editing tool or anti-viral treatment.…”

Preparation, characterization, and safety evaluation of poly(lactide-co-glycolide) nanoparticles for protein delivery into macrophages

“…7,8,[11][12][13][14][15][16] Monocytes/macrophages are relatively long-lived cells since HIV has very low cytopathic effects on them, making them a persistent reservoir of HIV regardless of the presence of highly active antiretroviral therapy. 8,[15][16][17] Monocytes and macrophages express efflux transporters, which contribute to maintain subtherapeutic concentrations of antiretroviral medications in these cells and may explain why macrophages are sanctuaries for HIV. 18 Therefore, eliminating or preventing viral infection in macrophages is a key element to achieve viral eradication, and new strategies to enhance penetration of antiviral therapeutics in macrophages are thus urgently needed.…”

HIV-1 Nef drives macrophages into hiding

“…Although highly active antiretroviral therapy (HA-ART) has been extraordinarily effective at reducing the morbidity and mortality of HIV infection, HA-ART does not remove latent virus from all cellular reservoirs. 2 Macrophages residing in tissues are potential cellular reservoirs that could contribute to the difficulty in eradicating HIV infection. 3 Furthermore, invasion of tissues by HIV-laden macrophages may contribute to HIV-associated pathologies.…”