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Francisco
A. Gonzalez-Scarano, M.D.
Professor, Department of Neurology/Microbiology
Chair, Dept. of Neurology
University of Pennsylvania
3 West Gates
Philadelphia, PA 19104-4283
Tel (215) 662-3360, 662-3389; Fax (215) 662-3362
email: scarano@mail.med.upenn.edu
Click here for selected publications since Dr. Gonzalez-Scarano's arrival at Penn
RESEARCH INTERESTS
Viral neurotropism RESEARCH TECHNIQUES
virology; tissue culture, molecular cloning, and expression in vaccinia/baculovirus and other systemsRESEARCH SUMMARY
Our laboratory studies viral tropism, 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 by indirect effects from infection of microglia. We are currently using primary brain tissue to determine the tropism of isolates for microglia and oligodendrocytes, and toward defining the molecular basis for microglial-tropism of selected viral strains, and the cellular basis for differential tropism, particularly the use of specific chemokine coreceptors for entry in microglia. To this end we have cloned viral envelope genes from the CNS of infected individuals, and used them in a number of entry assays, including the preparation of pseudotypes. We are are also investigating the chemokine receptor expression in human brain, particularly in neurons, and in cultured microglia, and the intracellular response to chemokine binding in neurons and glia.
A second group of projects studies La Crosse virus, a common cause of pediatric encephalitis. As a critical component in neurotropism, we are defining the entry pathway for La Crosse virus using recombinant proteins expressed in baculovirus and pseudotype assays, and we are developing a system for reverse genetics for this virus. The pseudotype system faithfully represents the tropism characteristics of the wild type viruses themselves, providing a mechanism for the detailed analysis of structure-function relationships, and for the potential isolation of a cellular receptor for La Crosse. The latter project is now ongoing.
KEY WORDS:
Virology; neurotropism; virus receptors
