Effect of human immunodeficiency virus on blood-brain barrier integrity and function: an update

Atluri, Venkata Subba Rao; Hidalgo, Manuel; Samikkannu, Thangavel; Kurapati, Kesava Rao Venkata; Jayant, Rahul Dev; Sagar, Vidya; Nair, Madhavan

doi:10.3389/fncel.2015.00212

Cited by 110 publications

(95 citation statements)

References 97 publications

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“…However, despite the significant advances of cART (combined anti-retroviral therapy), the incidence of neurocognitive complications in the brain associated with HIV infection persists (Ene et al, 2011, Dahal et al, 2015), which partially results from the limited efficiency by which many of these drugs cross the blood-brain barrier (BBB) (Heaton et al, 2011, Atluri et al, 2015). Severe side effects, toxicities, compliance problems, and the emergence of drug-resistant strains further complicate the use of this therapy (Kaul et al, 2001, Wu et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Electro-Magnetic Nano-Particle Bound Beclin1 siRNA Crosses the Blood–Brain Barrier to Attenuate the Inflammatory Effects of HIV-1 Infection in Vitro

Rodriguez

Kaushik

Lapierre

et al. 2016

J Neuroimmune Pharmacol

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The purpose of this study was to evaluate a novel drug delivery system comprised of ferric-cobalt electro-magnetic nano-material (CoFe2O4@ BaTiO3; MENP) bound to siRNA targeting Beclin1 (MENP-siBeclin1) to cross the blood-brain barrier (BBB) and attenuate the neurotoxic effects of HIV-1 infection in the central nervous system following on-demand release of siRNA using an in vitro primary human BBB model. Beclin1 is a key protein in the regulation of the autophagy pathway and we have recently demonstrated the importance of Beclin1 in regulating viral replication and viral-induced inflammation in HIV-1-infected microglia. The MENP-siBeclin1 nano-formulation did not compromise the physiological function or integrity of the BBB model. Furthermore, the in vitro BBB data revealed that MENP-siBeclin1 could efficiently attenuate viral replication, viral-induced inflammation and silence Beclin1 protein expression in HIV-1-infected microglial cells within the model system. In addition, the cytotoxic effects of direct treatment with siBeclin1 and MENP alone or in nano-formulation on primary human neuronal cells showed a minimal amount of cell death. Overall, the data shows that the nano-formulation can silence the BECN1 gene as an effective mechanism to attenuate HIV-1 replication and viral-induced inflammation in the context of the BBB.

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Section: Introductionmentioning

confidence: 99%

Electro-Magnetic Nano-Particle Bound Beclin1 siRNA Crosses the Blood–Brain Barrier to Attenuate the Inflammatory Effects of HIV-1 Infection in Vitro

Rodriguez

Kaushik

Lapierre

et al. 2016

J Neuroimmune Pharmacol

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“…Interestingly, over the course of this time, cells of the myeloid lineage, even though CD4 + , have been shown to less susceptible to virus-induced cytopathic effect and cell death with a drop in cell numbers much less evident during disease progression [16]. In addition, this cell lineage has been shown to be able to traverse various endothelial cell barriers, including the blood-brain barrier, allowing the infected circulating cell of the monocytic lineage to transport HIV into tissues as perivascular macrophages [17,18]. Once in tissues, the emerging infectious HIV-1 particle can then go on to infect other resident cells of that tissue.…”

Section: Introductionmentioning

confidence: 99%

Myelomonocytic Cell Lines in Modeling HIV-1 Infection of the Bone Marrow

Nonnemacher¹,

Quiterio²,

Allen³

et al. 2017

Biology of Myelomonocytic Cells

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Human immunodeficiency virus type 1 (HIV-1), the etiologic agent of acquired immunodeficiency syndrome (AIDS), primarily infects T cells and cells of the monocyte-macrophage lineage. This is due to the presence of the cell surface receptor CD4 and the coreceptors, CXCR4, and CCR5. While the T-cell has classically been the cell type associated with HIV-1 disease progression, cells of the monocyte-macrophage lineage have also been shown to play a major role in this viral pathologic process. Classically, this has involved monocytic cells in the peripheral blood and tissue macrophages, however, over the course of HIV disease, the promyelomonocytic cells of the bone marrow (BM) have also been shown to play a role in pathogenesis retroviral disease in that they play an integral role in the reseeding of the periphery and end-organ tissues. This has involved an initial infection of the bone marrow hematopoietic progenitor cells. Given this observation, over the years there have been a number of cell lines that have been developed and provided valuable insights into research questions surrounding HIV-1 infection of the monocyte-macrophage cell lineage. In this regard, we will examine the biological and immunological properties of these BM-derived cell lines with respect to their utility in exploring the pathogenesis of HIV-1 in humans.

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“…The mechanism by which human immunodeficiency virus (HIV) disrupts BBB and facilitates entry into brain, resulting in NeuroAIDS has been extensively studied. Specifically, HIV infection affects constituent proteins associated with the gap junction and astrocytes in BBB [28, 29]. The source of PERV RNA and mechanism of crossing BBB are currently under investigation.…”

Section: Discussionmentioning

confidence: 99%

Transmission of Porcine Endogenous Retrovirus Produced from Different Recipient Cells In Vivo

et al. 2016

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Humanized pigs have been developed to reduce the incidence of immune rejection in xenotransplantation, but significant concerns remain, such as transmission of viral zoonosis. Porcine endogenous retroviruses (PERV), which exist in the genome of pigs, are produced as infectious virions from all porcine cells and cause zoonosis. Here, we examined the possibility of zoonosis of hosts under conditions of immune suppression or xenotransplantation of cells producing host-adapted viruses. Upon transplantation of PERV-producing porcine cells into mice, no transmission of PERV was detected, whereas, transmission of PERV from mice transplanted with mouse-adapted PERV-producing cells was detected. In addition, the frequency of PERV transmission was increased in CsA treated mice transplanted with PERV-producing murine cells, compared with PERV-producing porcine cells. Transmission of PERV to host animals did not affect weight but immune responses, in particular, the number of T cells from PERV-transmitted mice, were notably reduced. The observed risk of PERV zoonosis highlights the requirement for thorough evaluation of viral zoonosis under particular host conditions, such as immunosuppressive treatment and transplantation with host-adapted virus-producing cells.

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Effect of human immunodeficiency virus on blood-brain barrier integrity and function: an update

Cited by 110 publications

References 97 publications

Electro-Magnetic Nano-Particle Bound Beclin1 siRNA Crosses the Blood–Brain Barrier to Attenuate the Inflammatory Effects of HIV-1 Infection in Vitro

Electro-Magnetic Nano-Particle Bound Beclin1 siRNA Crosses the Blood–Brain Barrier to Attenuate the Inflammatory Effects of HIV-1 Infection in Vitro

Myelomonocytic Cell Lines in Modeling HIV-1 Infection of the Bone Marrow

Transmission of Porcine Endogenous Retrovirus Produced from Different Recipient Cells In Vivo

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