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Journal of Virology, August 2008, p. 7591-7600, Vol. 82, No. 15
0022-538X/08/$08.00+0     doi:10.1128/JVI.00768-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Human Immunodeficiency Virus Type 1 Infection Increases the In Vivo Capacity of Peripheral Monocytes To Cross the Blood-Brain Barrier into the Brain and the In Vivo Sensitivity of the Blood-Brain Barrier to Disruption by Lipopolysaccharide{triangledown}

Hongwei Wang,1 Jinglin Sun,1 and Harris Goldstein1,2*

Departments of Microbiology & Immunology,1 Pediatrics, Albert Einstein College of Medicine, Bronx, New York 104612

Received 8 April 2008/ Accepted 21 May 2008

Human immunodeficiency virus type 1 (HIV-1), introduced into the brain by HIV-1-infected monocytes which migrate across the blood-brain barrier (BBB), infects resident macrophages and microglia and initiates a process that causes HIV-1-associated neurocognitive disorders. The mechanism by which HIV-1 infection circumvents the BBB-restricted passage of systemic leukocytes into the brain and disrupts the integrity of the BBB is not known. Circulating lipopolysaccharide (LPS), which can compromise the integrity of the BBB, is significantly increased in HIV-1-infected individuals. We hypothesized that HIV-1 infection increases monocyte capacity to migrate across the BBB, which is further facilitated by a compromise of BBB integrity mediated by the increased systemic LPS levels present in HIV-1-infected individuals. To investigate this possibility, we examined the in vivo BBB migration of monocytes derived from our novel mouse model, JR-CSF/EYFP mice, which are transgenic for both a long terminal repeat-regulated full-length infectious HIV-1 provirus and ROSA-26-regulated enhanced yellow fluorescent protein. We demonstrated that JR-CSF/EYFP mouse monocytes displayed an increased capacity to enter the brain by crossing either an intact BBB or a BBB whose integrity was partially compromised by systemic LPS. We also demonstrated that the JR-CSF mouse BBB was more susceptible to disruption by systemic LPS than the control wild-type mouse BBB. These results demonstrated that HIV-1 infection increased the ability of monocytes to enter the brain and increased the sensitivity of the BBB to disruption by systemic LPS, which is elevated in HIV-1-infected individuals. These mice represent a new in vivo system for studying the mechanism by which HIV-1-infected monocytes migrate into the brain.

* Corresponding author. Mailing address: Albert Einstein College of Medicine, Forchheimer Building, Room 408, 1300 Morris Park Avenue, Bronx, NY 10461. Phone: (718) 430-2156. Fax: (718) 430-2374. E-mail: hgoldste{at}aecom.yu.edu

{triangledown} Published ahead of print on 28 May 2008.

Journal of Virology, August 2008, p. 7591-7600, Vol. 82, No. 15
0022-538X/08/$08.00+0     doi:10.1128/JVI.00768-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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