Immunoperoxidase detection of yellow fever virus after natural and experimental infections

Accurate diagnosis of fatal Yellow Fever (YF) is important for surveillance and prevention of epidemics in regions where the virus is endemic. Immunoperoxidase (IP) staining for viral antigen offers a means to both document infection and investigate pathogenic mechanisms. We developed an indirect IP staining assay for YF, which was used to detect YF antigen in histologic section of human liver from patients with fatal natural infections, and suckling mouse brains experimentally inoculated with an unattenuated neurotropic strain of YF virus. In human liver, specific IP staining was present in the cytoplasm of hepatocytes, but in mouse brain, specific IP staining was localized within nuclei of neurons. The distribution of IP staining corresponded to the location of degenerative morphologic changes within cells; however, IP staining was more widespread than expected on the basis of histopathologic lesions. Furthermore, the degree of inflammation was disproportionately mild compared to the extent of infection, i.e. distribution of YF antigen, both in human liver and suckling mouse brain. The results suggest that the pathogenesis of YF in humans and suckling mice is overwhelming viral infection with minimal associated host immunological and/or inflammatory response in tissues.