eBriefing

The Virus-Cell Dance: HIV Neuropathology in the HAART Era

The Virus-Cell Dance
Reported by
Jill U. Adams

Posted February 27, 2007

Presented By

Neuroimmunology Discussion Group

Overview

HIV-infected people treated with highly active antiretroviral therapy (HAART) live longer and are less likely to develop AIDS than those not receiving therapy. They have lower viral burdens and often their immune systems recover at least in part. In spite of this success, however, many patients continue to develop progressive neurological symptoms, albeit milder ones, at the same rates as patients in the pre-HAART era. Five to ten percent of HIV-infected people end up with some degree of dementia.

The central nervous system (CNS) is a major target for HIV infection. But the virus does not infect neurons; rather, it invades and replicates in microglia and activates astrocytes. Pathological consequences include neuronal dysfunction and cell death. Three approaches to deepening the investigation of CNS immune response to HIV were discussed at the New York Academy of Sciences on October 11, 2006, in a meeting sponsored by the Neuroimmunology Discussion Group.

Use the tabs above to view the meeting report and multimedia presentations.

Web Sites

National Institute of Allergy and Infectious Diseases
Overview of HIV infection and AIDS.

eMedicineHealth.com
Consumer health resource providing information on the relationship between HIV infection and dementia.

HIVInSite
Knowledge-based information on AIDS dementia complex.

Neuropathology at Northeastern Ohio Universities College of Medicine
Illustrated interactive course for medical students and residents.


Books

Booss J, Esiri MM. 2003. Viral Encephalitis in Humans. ASM Press, Washington, DC.
Amazon

Gifford AL, Lorig K, Laurent D, Gonzalez V. 2000. Living Well With HIV and AIDS. Bull Publishing Co., Boulder, CO.
Amazon

Price RW, Sidtis JJ, eds. 1996. The Cellular Basis of Central Nervous System HIV-1 Infection and the AIDS Dementia Complex. Haworth Press, New York, NY.
Amazon


Journal Articles

Microglia and HIV Encephalitis

Cosenza MA, Zhao ML, Si Q, et al. 2002. Human brain parenchymal microglia express CD14 and CD45 and are productively infected by HIV-1 in HIV-1 encephalitis. Brain Pathol. 12: 442-55.

Cosenza-Nashat MA, Si Q, Zhao ML, Lee SC. 2006. Modulation of astrocyte proliferation by HIV-1: Differential effects in productively infected, uninfected, and Nef-expressing cells. J. Neuroimmunol. 178: 87-99.

Kim MO, Suh H-S, Si Q, et al. 2006. Anti-CD45RO suppresses human immunodeficiency virus type 1 replication in microglia: Role of Hck tyrosine kinase and implications for AIDS dementia. J. Virol. 80: 62-72. FULL TEXT

Suh H.-S, Kim M-O, Lee SC. 2005. Inhibition of granulocyte-macrophage colony-stimulating factor signaling and microglial proliferation by anti-CD45RO: Role of Hck tyrosine kinase and phosphatidylinositol 3-kinase/Akt. J. Immunol. 174: 2712-2719. FULL TEXT

A New Model of HIV Infection in Mice and its Application to the Study of HIV Neuropathogenesis

Kim S-Y, Li J, Bentsman G, et al. 2004. Microarray analysis of changes in cellular gene expression induced by productive infection of primary human astrocytes: implications for HAD. J. Neuroimmunol. 157: 17-26.

Nitkiewicz J, Chao W, Bentsman G, et al. 2004. Productive infection of primary murine astrocytes, lymphocytes, and macrophages by human immunodeficiency virus type 1 in culture. J. Neurovirol. 10: 400-408.

Potash MJ, Chao W, Bentsman G, et al., 2005. A mouse model for study of systemic HIV-1 infection, antiviral immune responses, and neuroinvasiveness. Proc. Natl. Acad. Sci. USA 102: 3760-3765. FULL TEXT

Wang Z., Trillo-Pazos G, Kim SY, et al. 2004. Effects of human immunodeficiency virus type 1 on astrocyte gene expression and function: potential role in neuropathogenesis. J. Neurovirol. 10: 25-32.

The Contribution of Astrocytes to Immune Responses in CNS Viral Infection

Coley SE, Lavi E, Sawicki SG, et al. 2005. Recombinant mouse hepatitis virus strain A59 from cloned, full-length cDNA replicates to high titers in vitro and is fully pathogenic in vivo. J. Virol. 79: 3097-3106. FULL TEXT

Li, Y, Fu L, Gonzales DM, Lavi E. 2004. Coronavirus neurovirulence correlates with the ability of the virus to induce proinflammatory cytokine signals from astrocytes and microglia. J. Virol. 78: 3398-3406. FULL TEXT

Speakers

Sunhee C. Lee, MD

Albert Einstein College of Medicine, Yeshiva University
e-mail | web site | publications

Sunhee Lee is professor of pathology at the Albert Einstein College of Medicine (AECOM) at Yeshiva University. Her research interest is the inflammatory mechanism of human glial cell activation and the role of pathogens such as human immunodeficiency virus and the opportunistic fungal organism Cryptococcus neoformans. Lee focuses on translational research. She defines the involvement of inflammatory mediators in human brain diseases including AIDS, multiple sclerosis, and stroke. The search for potential therapeutics is always a goal.

Lee received her MD from Seoul National University in Korea. After a brief period of clinical practice, she entered the Pathology Residency Program at the AECOM, where, under the guidance of Dennis Dickson, she was introduced to academic neuropathology. She went to the University of Maryland to further her training in biochemistry and molecular biology. She then returned to AECOM, joining the research team in the Department of Pathology, where she now leads her own laboratory specializing in microglial cell pathobiology.

David J. Volsky, PhD

Columbia University Medical Center and Molecular Virology Division, St. Luke's-Roosevelt Hospital Center
e-mail | publications

David Volsky is professor of pathology at the College of Physicians and Surgeons at Columbia University and the director of the Molecular Virology Laboratory at St. Luke's-Roosevelt Hospital. His research interests center on the neuropathogenesis of HIV infection and how various immune cells in the brain mediate that process.

Volsky received his PhD in biochemistry from the Hebrew University in Jerusalem, Israel. His postdoctoral studies were in tumor biology and virology with George Klein at the Karolinska Institute in Stockholm, Sweden. Volsky then joined the faculty at the University of Nebraska Medical Center in Omaha where he established and directed the molecular biology laboratory there, one of the first dedicated to HIV/AIDS research in the country. In 1987, Volsky moved to the College of Physicians and Surgeons at Columbia University and became director of the Molecular Virology Division at St. Luke's Roosevelt Hospital Center.

Ehud Lavi, MD

Weill Medical College, Cornell University
e-mail | web site | publications

Ehud Lavi is professor of pathology and laboratory medicine and chief of the Neuropathology Service at Weill Medical College of Cornell University. His research interest is in neurovirology and neuroimmunology. Lavi is investigating an experimental model of multiple sclerosis in mice: coronavirus-induced demyelination. The main focus of investigation is the interaction between viruses and the central nervous system (CNS) and includes the role of astrocytes and microglia in cytokine signaling in the CNS as well as the role of the viral glycoprotein in neurotropism.

Lavi received his MD from the Technion, Israel Institute of Technology, and did a neurology residency at Hadassah Hospital, at the Hebrew University School of Medicine in Jerusalem, Israel. Following a research fellowship in neurovirology at the University of Pennsylvania and the Wistar Institute in Philadelphia, he trained in anatomic pathology at Pennsylvania Hospital in Philadelphia, followed by a neuropathology fellowship at the University of Pennsylvania. In 1991, Lavi joined the faculty of the University of Pennsylvania, where he served as attending neuropathologist until 2005 when he moved to Cornell University.


Jill U. Adams

Jill U. Adams is a scientist-turned-science-writer based in Albany, New York.