Affiliation: | aDepartments of Microbiology and Immunology, The University of Texas Medical Branch, Galveston TX 77555-0609, USA bDepartment of Pathology, The University of Texas Medical Branch, Galveston TX 77555-0609, USA cSealy Center for Vaccine Development, The University of Texas Medical Branch, Galveston TX 77555-0609, USA dCenter for Biodefense and Emerging Infectious Diseases, The University of Texas Medical Branch, Galveston TX 77555-0609, USA eDepartment of Internal Medicine, The University of Texas Medical Branch, Galveston TX 77555-0609, USA |
Abstract: | Viscerotropic yellow fever virus (YFV) infection occurs primarily in humans and non-human primates. Lack of an appropriate small animal model of viscerotropic YFV infection has been a major deterrent to molecular studies of viscerotropism. A hamster model of viscerotropic YFV infection has recently been described; however, these studies have focused on hamster-viscerotropic strains of YFV (including Asibi hamster P7 virus) that caused outward clinical signs of infection and mortality. In order to map more closely the molecular determinants of viscerotropism in the hamster model, a second sequential series of seven liver-to-liver passages of Asibi virus was undertaken through hamsters to generate Asibi P7b virus. Asibi hamster P7b virus did not cause clinically detectable signs of YFV infection; however, high quantities of circulating virus were isolated from the serum, and microscopic evaluation of the liver and spleen demonstrated histopathological lesions consistent with YFV infection. The genomic sequence of Asibi P7b virus was determined and compared to wild-type Asibi virus and the lethal, hamster-viscerotropic Asibi P7 virus and found to differ by only two amino acids in the envelope protein, E-98 and E-331. |