This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sun, J.
Right arrow Articles by Goldstein, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sun, J.
Right arrow Articles by Goldstein, H.

 Previous Article  |  Next Article 

Journal of Virology, June 2008, p. 5562-5572, Vol. 82, No. 11
0022-538X/08/$08.00+0     doi:10.1128/JVI.02618-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Increased In Vivo Activation of Microglia and Astrocytes in the Brains of Mice Transgenic for an Infectious R5 Human Immunodeficiency Virus Type 1 Provirus and for CD4-Specific Expression of Human Cyclin T1 in Response to Stimulation by Lipopolysaccharides{triangledown}

Jinglin Sun,1,2 Jian Hua Zheng,1 Mengliang Zhao,3 Sunhee Lee,3 and Harris Goldstein1,2*

Departments of Microbiology & Immunology,1 Pediatrics,2 Pathology, Albert Einstein College of Medicine, Bronx, New York 104613

Received 9 December 2007/ Accepted 12 March 2008

Inflammatory mediators and viral products produced by human immunodeficiency virus (HIV)-infected microglia and astrocytes perturb the function and viability of adjacent uninfected neuronal and glial cells and contribute to the pathogenesis of HIV-associated neurocognitive disorders (HAND). In vivo exposure to lipopolysaccharide (LPS) activates parenchymal microglia and astrocytes and induces cytokine and chemokine production in the brain. HIV-infected individuals display increased circulating LPS levels due to microbial translocation across a compromised mucosa barrier. We hypothesized that HIV-infected microglia and astrocytes display increased sensitivity to the proinflammatory effects of LPS, and this combines with the increased levels of systemic LPS in HIV-infected individuals to contribute to the development of HAND. To examine this possibility, we determined the in vivo responsiveness of HIV-infected microglia and astrocytes to LPS using our mouse model, JR-CSF/human cyclin T1 (JR-CSF/hu-cycT1) mice, which are transgenic for both an integrated full-length infectious HIV type 1 (HIV-1) provirus derived from the primary R5-tropic clinical isolate HIV-1JR-CSF regulated by the endogenous HIV-1 long terminal repeat and the hu-cycT1 gene under the control of a CD4 promoter. In the current report, we demonstrated that in vivo-administered LPS more potently activated JR-CSF/hu-cycT1 mouse microglia and astrocytes and induced a significantly higher degree of monocyte chemoattractant protein production by JR-CSF/hu-cycT1 astrocytes compared to that of the in vivo LPS response of control littermate mouse microglia and astrocytes. These results indicate that HIV infection increases the sensitivity of microglia and astrocytes to inflammatory stimulation and support the use of these mice as a model to investigate various aspects of the in vivo mechanism of HIV-induced neuronal dysfunction.

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

{triangledown} Published ahead of print on 19 March 2008.

Journal of Virology, June 2008, p. 5562-5572, Vol. 82, No. 11
0022-538X/08/$08.00+0     doi:10.1128/JVI.02618-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Miron, V. E., Zehntner, S. P., Kuhlmann, T., Ludwin, S. K., Owens, T., Kennedy, T. E., Bedell, B. J., Antel, J. P. (2009). Statin Therapy Inhibits Remyelination in the Central Nervous System. Am. J. Pathol. 174: 1880-1890 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»