Function of ankyrin repeat proteins in cowpox virus (CPXV)
Zusammenfassung der Projektergebnisse
Orthopoxvirus (OPV) genomes consist of a highly conserved central portion primarily encoding genes for poxvirus replication, while sequences towards the ends are more variable. Genes found in these regions encode proteins that govern virulence and immune modulation. One group of these variable genes encode for ankyrin repeat proteins (ARPs). ARPs are common in eukaryotic cells and mainly mediate proteinprotein interactions. Some of the ARPs in poxviruses also contain an additional C-terminal F-box domain that is commonly linked to proteasomal degradation. Modified vaccinia virus Ankara (MVA) only specifies one ARP that is encoded by gene 186R and is essential for completion of the viral life cycle in mammalian cells. Sequence analysis predicted that CPXV specifies three ARPs that share high sequence similarity, one of which is called BR211 and represents the orthologue of MVA 186R. We hypothesized that the three ARPs BR006, BR211 and BR220 confer transition into the post-replicative phase of CPXV but that each does so in different sets of host cells. We further surmised that the three CPXV ARPs retarget cellular and viral proteins in a fashion that is dependent on certain phases of virus replication. We tested the first part of the hypothesis in the first specific aim: Cell-type specific complementation of the deletion of all BR211-like ARPs in CPXV or MVA. We were unable to complete aim 2, “Identification of BR211-interacting proteins in different phases of CPXV replication”, because we refuted the original hypothesis.
Projektbezogene Publikationen (Auswahl)
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(2012). Cowpox virus serpin CrmA is necessary but not sufficient for the red pock phenotype on chicken chorioallantoic membranes. Virus Res. 163(1):254-261
Roth SJ, Klopfleisch R, Osterrieder N, Tischer BK
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(2012). Viral bacterial artificial chromosomes: generation, mutagenesis, and removal of mini-F sequences. J Biomed Biotechnol. 2012:472537
Tischer BK, Kaufer BB
