Abstract
Human immunodeficiency virus (HIV) is still a serious global health concern responsible for more than 25 million deaths in last three decades. More than 34 million people are living with HIV infection. Macrophages and CD4+ T cells are the principal targets of HIV-1. The pathogenesis of HIV-1 takes different routes in macrophages and CD4+ T cells. Macrophages are resistant to the cytopathic effect of HIV-1 and produce virus for longer periods of time. In addition, macrophages being present in every organ system thus can disseminate virus to the different anatomical sites leading to the formation of viral sanctuaries. Complete cure of HIV-1 needs better understanding of viral pathogenesis in these reservoirs and implementation of knowledge into robust therapeutic products. In this review we will focus on the unique relationship between HIV-1 and macrophages. Furthermore, we will describe how successful antiretroviral therapy (ART) is in suppressing HIV and novel molecular and cellular strategies against HIV-1 in macrophages.
Highlights
Human immunodeficiency virus type 1 (HIV-1) can infect several types of immune cells, macrophages and CD4+ T lymphocytes cells are the principal targets of HIV-1 in human body [1,2]
In monocyte derived macrophages (MDMs) exogenously added recombinant Nef regulates the expression of several genes in a short time span (2 hours). These findings indicate a robust transcriptional programming governed by Nef protein leading to the production and secretion of soluble factors which in turn activates STAT1 and STAT3 in primary monocytes/macrophages [20,77]
Expression of Nef by these infected CD4+ T cells is necessary for anti-apoptotic behavior presence of macrophages further enhances the number of non-apoptotic cells via intercellular contacts mediated by TNF stimulation [84]. This may be the one of the mechanisms of promotion of HIV-1 reservoir in T cells by macrophages. Another regulatory protein of HIV, Tat has been reported to stimulate the expression of TRAIL TNF related apoptosis-induced ligand (TRAIL) in U937, monocytes and primary macrophages [85,86], which results in the apoptosis of uninfected cells (Figure 2)
Summary
Human immunodeficiency virus type 1 (HIV-1) can infect several types of immune cells, macrophages and CD4+ T lymphocytes cells are the principal targets of HIV-1 in human body [1,2]. This may be the one of the mechanisms of promotion of HIV-1 reservoir in T cells by macrophages Another regulatory protein of HIV, Tat has been reported to stimulate the expression of TRAIL TNF related apoptosis-induced ligand (TRAIL) in U937, monocytes and primary macrophages [85,86], which results in the apoptosis of uninfected cells (Figure 2). Several kinds of new approaches have been employed in reactivating HIV including the use of histone deacetylase inhibitors (HDACi) such as valproic acid (VPA), trichostatin (TSA), suberoylanilide hydroxyamic acid (SAHA) and sodium butyrate, methylation inhibitors including BIX01294, 5-aza-2′deoxycytidine (Aza-CdR) and chaetocin, NFκB activators for example TNF-α and bryostatin and protein kinase C modulators and immune modulators including IL-7 and IL-15 [96,105,116,173] These new compounds have shown significant results in reactivating latency in CD4+ T cells and are at different stages of development. Ignoring one or other viral reservoir will not result in any favorable outcome
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