Ecology and Pathogenesis of Zoonotic Viruses in Central Asia

The infection of human beings by viruses that are transmitted from animals represent some of the most devastating diseases known. It was the goal of this project to investigate these viruses at contrasting scales, in order to understand the critical components of their role in human disease. The experiments performed in this body of work range from the scale of environmental ecologies to molecular mechanisms. We have developed a novel approach to ELISA analysis and performed these analyses in the field so that we could describe a novel strain of Tick-Borne Encephalitis Virus (TBEV) in Kyrgyzstan. This new strain was found to be endemic and circulates at elevations higher, and latitudes more southerly, than any published accounts to date. We have also shown that the rodent reservoir for TBEV in Kyrgyzstan is the Himalayan Field Mouse (Apodemus pallipes), which has never before been shown to harbor zoonotic viruses. We collected convincing data to suggest that A. pallipes also harbors a hantavirus that may resemble Puumala virus. Finally, we have demonstrated how a hantavirus (Hantaan Virus; HTNV) is able to modulate the type-I interferon system in a novel manner, dependent on the RNA binding domain of the nucleocapsid protein (N). This novel mechanism of type-I interferon modulation is an example of an additional function of this already multifunctional protein. In summary, these data represent an original approach, which integrates molecular mechanisms with epidemiological data, in order to gain a more complete appreciation of the systemic variables of zoonotic viral dynamics.