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Imprint
Molecular Determinants of Lyssavirus-Replication
Project
Project code: 76572622
Contract period: 01.01.2008
- 31.12.2010
Purpose of research: Basic research
Bats act as reservoirs for many zoonotic viruses. Reasons for this preferential reservoir function and molecular requirements for trans-species transmission and establishment of bat-derived viruses in new hosts are unknown. Among the bat-associated viruses are Lyssaviruses. Lyssaviruses comprise rabies virus (RV) circulating in carnivores and bat associated viruses, making this a suitable model to investigate virus adaptation to different hosts. In the proposed project we plan to assay for virus-host protein interactions that explain host specific replication of different lyssaviruses. Murine and human cells are infected with bat and non-bat lyssaviruses and protein interactions required for efficient replication in non-bat systems are identified in a comparative mass spectrometry screen, in which RV and bat virus proteomes of purified intracellular subviral complexes are compared. Differences between RV and bat virus complexes in their cell protein content are supposed to reflect host specific variations. Influences of identified proteins on virus replication are evaluated and domains/motifs involved in host specific interactions are mapped. The relevant sequences are exchanged between recombinant RV and bat viruses and their influence on host specific virus replication of the recombinant viruses are investigated in cell culture and in vivo. Recombinant bat viruses with proteins or protein-domains adopted from RV will for the first time allow systematic characterization of molecular processes in host specific lyssavirus replication. Identification of host-related differences will contribute to the risk assessment related to infection of new hosts by bat-lyssaviruses and will provide a basis for further investigation of molecular principles of virus replication in bat reservoirs.
Section overview
Subjects
- Animal health
Funding programme
Excutive institution
FLI - Institute of Molecular Virology and Cell Biology (FLI - IMVZ)
