faculty photo

Francisco Gonzalez-Scarano, MD

Emeritus Professor of Neurology
Department: Neurology

Contact information
Department of Neurology
Hospital of the University of Pennsylvania
3 West Gates
3400 Spruce Street
Philadelphia, PA 19104-4283
Office: (215) 662-3360
Fax: (215) 662-3362
B.A. (Economics)
Yale University , 1971.
Northwestern University, 1975.
Post-Graduate Training
Intern in Medicine, Hospital of the University of Pennsylvania, 1975-1976.
Resident in Neurology, Hospital of the University of Pennsylvania, 1976-1979.
Post-Doctoral Fellow, Department of Microbiology, University of Pennsylvania (Laboratory of Neal Nathanson), 1979-1982.
Fellow, National Multiple Sclerosis Society , 1979-1982.
Visiting Worker National Institute for Medical Research, Division of Virology Mill Hill, London (Laboratory of John Skehel), 1981-1982.
Diplomate of the National Board of Medical Examiners, 1976.
Board Certified in Neurology, 1980.
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Description of Research Expertise

Research Interests
HIV Neuropathogenesis, Neurovirulence, Bunyaviruses.

Key words: HIV, microglia, neuropathogenesis, HIV Dementia.

Description of Research
Our laboratory studies viral neurotropism, in two groups of viruses.

Human immunodeficiency virus causes a dementia, in addition to its primary effects on the immune system. The projects in the laboratory are primarily oriented to defining the pathophysiology of this HIV Dementia, which may be mediated by either direct infection of astrocytes, neurons and oligodendrocytes, or more likely, by indirect effects from infection of microglia. Current projects involve the analysis of CD4 dependence of HIV strains and the potential for development of neutralization-resistant strains in the CNS environment. An SIV project will look at viral evolution within the CNS, including analysis of viral genomes at the level of single cells.

La Crosse virus is a member of the Bunyaviridae, a large family of viruses that includes the hantaviruses, which cause hantavirus pulmonary syndrome. La Crosse is a common cause of pediatric encephalitis. Current La Crosse projects look at the regions of the viral glycoproteins responsible for entry into muscle cells, and at the use of siRNA to inhibit La Crosse infections.

Rotation Projects for 2006-2007
1. Role of NSs in inhibition of siRNA in La Crosse.
2. Analysis of SIV gp120 sequences recovered from CSF and brain.
3. gp120-CD4 interaction of HIV isolates from the CNS.
4. gag assembly in macrophages.

Lab personnel:
Wei Cao (Technician)
Maria Chen (Graduate Student)
Alexia Harrist (Graduate Student)
Tom Harvey (Technician)
Matthew Plassmeyer (Graduate Student)
Elena Ryzhova (Research Associate)
Samantha Soldan (Postdoctoral Fellow)
Karen Stachelek (Technician)

Selected Publications

Ryzhova E.V., Crino P, Shawver L., Westmoreland S.V., Lackner A.A., and González-Scarano. F. : Simian Immunodeficiency Virus Encephalitis: Analysis of envelope sequences from individual brain multinucleated giant cells and tissue samples. Virology 297: 57-67, 2002.

Ryzhova, E.V., Whitbeck,C., Canziani, G., Westmoreland, S.V., Cohen, G., Eisenberg, R., Lackner, A.A., and González-Scarano, F. : Rapid Progression to SAIDS Can Be Accompanied by Selection of CD4-independent gp120 Variants with Impaired Ability to Bind CD4 Journal of Virology 76: 7903-7090, 2002.

Chen, M.F., Westmoreland, S., Ryzhova, E.V., Martín-García, J., Soldan, S.S., Lackner, A., and González-Scarano F. : Simian Immunodeficiency Virus Envelope Compartmentalizes in Brain Regions Independent of Neuropathology. Journal of Neurovirology 12: 73-89, 2006.

Van der Meer, P., Goldberg, S.H., Fung, K.M., Sharer, L.R., González-Scarano, F., and Lavi, E. : Expression Pattern of CXCR3, CXCR4, and CCR3 Chemokine Receptors in the Developing Brain Journal of Neuropathology and Experimental Neurology 60: 25-32, 2001.

Soldan, S.S., Plassmeyer, M.L., Matukonis, M.K., and González-Scarano, F.: La Crosse virus Non-structural Protein NSs Counteracts the Effects of siRNA. Journal of Virology 79: 234-244, 2005.

González-Scarano, F. and Martín-García, J.: The Neuropathogenesis of AIDS. Nature Reviews in Immunology 5: 69-81, 2005.

Martín-García J., Cao W., Varela-Rohena A., Plassmeyer M.L., and González-Scarano F.: HIV-1 Tropism for the Central Nervous System: Brain-Derived Envelope Glycoproteins with Lower CD4-Dependence and Reduced Sensitivity to a Fusion Inhibitor. Virology 346: 169-179, 2006.

Plassmeyer, M.L., Soldan, S.S., Stachelek, K.M., Roth, S.M., Martín-García, J., and González-Scarano, F: Mutagenesis of the La Crosse virus glycoproteins supports a role for Gc (1066-1087) as the Fusion peptide. Virology 358, 2007.

Ryzhova, E., Aye, P., Harvey, T., Cao, W., Lackner, A., ad González-Scarano, F: Intrathecal humoral responses are inversely associated with the frequency of SIV M-tropic variants in the CNS. Journal of Virology 2009.

Harrist, A.V., Ryzhova, E.V., Harvey, T., and González-Scarano, F. : Anx2 interacts with HIV-1 Gag at phosphatidylinositol (4,5) bisphosphate-containing lipid rafts and increases viral production in 293T cells. PLoSONE 4(3): e5020, 2009.

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Last updated: 06/29/2009
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