Viral Infections and the Blood-Brain Barrier

2011

J Neuroinflammation

Elevated levels of cytokines/chemokines contribute to increased neuroinvasion of human immunodeficiency virus type 1 (HIV-1). Previous work showed that lipopolysaccharide (LPS), which is present in the plasma of patients with HIV-1, enhanced transcellular transport of HIV-1 across the blood-brain barrier (BBB) through the activation of p38 mitogen-activated protein kinase (MAPK) signaling in brain microvascular endothelial cells (BMECs). Here, we found that LPS (100 μg/mL, 4 hr) selectively increased interleukin (IL)-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF) release from BMECs. The enhancement of HIV-1 transport induced by luminal LPS was neutralized by treatment with luminal, but not with abluminal, antibodies to IL-6 and GM-CSF without affecting paracellular permeability as measured by transendothelial electrical resistance (TEER). Luminal, but not abluminal, IL-6 or GM-CSF also increased HIV-1 transport. U0126 (MAPK kinase (MEK)1/2 inhibitor) and SB203580 (p38 MAPK inhibitor) decreased the LPS-enhanced release of IL-6 and GM-CSF. These results show that p44/42 and p38 MAPK signaling pathways mediate the LPS-enhanced release of IL-6 and GM-CSF. These cytokines, in turn, act at the luminal surface of the BMEC to enhance the transcellular transport of HIV-1 independently of actions on paracellular permeability.

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide-enhanced transcellular transport of HIV-1 across the blood-brain barrier is mediated by luminal microvessel IL-6 and GM-CSF

Dohgu

Fleegal-DeMotta

2011

J Neuroinflammation

“…tick-borne encephalitis virus, canine distemper virus, and measles) through diapedesis (Chou and Dix, 1989;Marsh, 1984;Hurwitz et al, 1994). The vesicular-mediated endocytosis/transcytosis of viruses and the diapedesis of immune cells appear histologically similar to each other and to adsorptive endocytosis (AE).…”

Section: Introductionmentioning

confidence: 98%

Characterization of lectin-mediated brain uptake of HIV-1 GP120

Kastin

1998

J. Neurosci. Res.

The viral coat of the HIV-1 virus, gp120, has been shown to cross the blood-brain barrier (BBB) in lectin-like fashion by inducing adsorptive endocytosis (AE), a vesicular mechanism that could provide pathways into and across brain endothelial cells for virus and infected immune cells. Here, we extended those findings to show that gp120 slowly crossed the BBB with about 0.15% of an intravenously injected dose entering the brain after about 2 hr. The plant lectin glycoprotein wheat germ agglutinin (WGA) greatly enhanced gp120 crossing without disrupting the BBB. WGA enhanced the uptake of gp120 into all peripheral tissues studied, but the greatest percent increase occurred for brain, whereas another barrier tissue, the testis, had the least increase. Five other plant lectins tested had little or no effect on gp120 uptake by brain, suggesting a key role for sialic acid and N-acetyl-beta-D-glucosaminyl acid, the sugars to which WGA binds, in the uptake of gp120 by brain endothelial cells. WGA did not enhance the uptake of nonglycosylated gp120 and the uptake of gp120 was not self-inhibitable or altered by pretreatment of mice with aluminum. In conclusion, these studies show that gp120 crosses the BBB by a lectin-like mechanism resembling AE that is likely mediated by binding to specific sugar moieties and is rather selective for brain.

“…Some viruses first infect brain endothelium (togavirus, murine retrovirus, and possibly varicella-zoster) or the choroid plexus (togavirus and mumps) and then invade the CNS, a route that has been suggested for HIV (Bagasra et al, 1996;Falangola et al, 1995;Moses et al, 1993;Poland et al, 1995a;Wiley et al, 1986) and demonstrated for Simian Immunodeficiency Virus (Edinger et al, 1997;Mankowski et al, 1999;Strelow et al, 1998). Passage of infected immunocytes through the BBB has been postulated for a tick-borne encephalitis virus, canine distemper virus, and measles as well as for HIV (Chou and Dix, 1989;Nottet et al, 1996;Persidsky et al, 1997). Because of their sizes, free viruses and infected immunocytes cross the BBB by vesicular-related processes (Lossinsky et al, 1991;Marsh, 1984;Mellman et al, 1986).…”

Section: Hiv-1mentioning

confidence: 93%

“…The number of pathways by which viruses cross the BBB is small (Chou and Dix, 1989). Some viruses first infect brain endothelium (togavirus, murine retrovirus, and possibly varicella-zoster) or the choroid plexus (togavirus and mumps) and then invade the CNS, a route that has been suggested for HIV (Bagasra et al, 1996;Falangola et al, 1995;Moses et al, 1993;Poland et al, 1995a;Wiley et al, 1986) and demonstrated for Simian Immunodeficiency Virus (Edinger et al, 1997;Mankowski et al, 1999;Strelow et al, 1998).…”

Section: Hiv-1mentioning

confidence: 99%

In Vitro Methods in the Study of Viral and Prion Permeability Across the Blood–Brain Barrier

Nakaoke

2005

Cell Mol Neurobiol

(1) Infectious agents capable of entering the central nervous system (CNS) produce some of the most dreaded diseases known to man. The infectious agent within the CNS is often protected by the blood-brain barrier (BBB), shielded from endogenous and exogenous anti-infectious agents. (2) The use of in vitro methods offers many advantages to the study of how infectious agents interact with the BBB. Two such agents which negotiate the BBB early in the course of disease before damage to the BBB are the autoimmune deficiency syndrome virus, or human immunodeficiency virus 1, and scrapie prion. Our laboratories have used in vitro methods to study these agents. (3) Here, we review some of the results form our laboratories and those of others.