Yellow Fever (YF) virus causes hemorrhagic fever. It is a category A select agent and re-emerging disease in regions of South America and Africa. Currently, the molecular basis of viscerotropism of YF virus is poorly understood; however, the recent development of a small animal model for viscemtropic YF virus infection enables elucidation of the molecular determinants of YF virus viscerotropism. Detailed molecular characterization of the viscerotropic Asibi/hamster p7 virus will identify regions of the genome that are important in determining the viscerotropic phenotype. This will involve the following specific aims.
Aim 1 : Identification of the nucleotide and deduced amino acid changes present in hamster viscerotropic viruses by nucleotide sequence analysis. Comparison of the genomic sequence of the viscerotropic Asibi/hamster p7 virus with that of the parental Asibi/hamster p0 virus and other intermediate passage viruses will identify changes most likely to be important in the viscerotropic phenotype.
Aim 2 :Development of an infectious clone of YF virus to study the effects of mutant genes and gene regions on hamster viscerotropism. These studies will allow the identification of the region(s) of the YF virus genome that are involved in hamster viscerotropism.
Aim 3 : Identification of specific amino acid mutations involved in the hamster viscerotropic phenotype, and investigation of the molecular mechanism of hamster viscerotropism with respect to virus receptor interaction, liver pathology, and viremia. Detailed characterization of mutant viruses constructed in Aim 2 will identify potential mechanisms of viscerotropism in the hamster model.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
5F31AI054319-02
Application #
6756601
Study Section
Special Emphasis Panel (ZRG1-F05 (29))
Program Officer
Hernandez, Milton J
Project Start
2003-02-01
Project End
2004-07-26
Budget Start
2004-02-01
Budget End
2004-07-26
Support Year
2
Fiscal Year
2004
Total Cost
$12,267
Indirect Cost
Name
University of Texas Medical Br Galveston
Department
Pathology
Type
Schools of Medicine
DUNS #
800771149
City
Galveston
State
TX
Country
United States
Zip Code
77555
McArthur, Monica A; Xiao, Shu-Yuan; Barrett, Alan D T (2005) Phenotypic and molecular characterization of a non-lethal, hamster-viscerotropic strain of yellow fever virus. Virus Res 110:65-71