No abstract

The genomes of carlaviruses encode cysteine-rich proteins (CRPs) of unknown function. The 12 kDa CRP of chrysanthemum virus B (CVB), p12, has been shown previously to induce a hypersensitive response (HR) when expressed from potato virus X (PVX). This study demonstrated that a p12-induced HR was preceded by induction of a number of genes related to pathogenesis, stress and systemic acquired resistance. p12 localized predominantly to the nucleus. Interestingly, it was found that p12 bound both RNA and DNA in vitro, but notably exhibited a preference for DNA in the presence of Zn 2+ ions. Mutational analysis of the p12 conserved sequence motifs demonstrated that the basic motif is required for p12 translocation to the nucleus, thus representing part of the protein nuclear localization signal, whereas the predicted zinc finger motif is needed for both Zn 2+ -dependent DNA binding and eliciting an HR in PVX-infected leaves. Collectively, these results link, for the first time, nuclear localization of the protein encoded by a cytoplasmically replicating virus and its DNA-binding capacity with HR induction. Furthermore, these data suggest that p12 may mediate induction of the host genes by binding to the plant genomic DNA, and emphasize that CVB p12 is functionally distinct from other known nuclear-localized proteins encoded by the plant positive-stranded RNA viruses.

Erythrovirus B19 (B19V) is a member of the family Parvoviridae. Infection with B19V has been linked to a variety of diseases including erythroid, thyroid, neurological and autoimmune diseases. Here we show that infection of primary CD36+ cells with B19V coincides with downregulation of thyroid, retinoid, and estrogen hormone receptors. In addition we show changes in expression of a variety of related downstream signaling genes participating in cancer and cardiac-related diseases in B19V-infected erythroid primary cells.

Metabolic activation of many carcinogens leads to formation of reactive intermediates that form DNA adducts. These adducts are cytotoxic when they interfere with cell division. They can also cause mutations by miscoding during DNA replication. Therefore, an individual’s risk of developing cancer will depend on the balance between these processes as well as their ability to repair the DNA damage. Our hypothesis is that variations of genes participating in DNA damage repair and response pathways play significant roles in an individual’s risk of developing tobacco-related cancers. To test this hypothesis, 61 human B-lymphocyte cell lines from the International HapMap project were phenotyped for their sensitivity to the cytotoxic and genotoxic properties of a model methylating agent, N-nitroso-N-methylurethane (NMUr). Cell viability was measured using a luciferase-based assay. Repair of the mutagenic and toxic DNA adduct, O 6-methylguanine (O 6-mG), was monitored by LC-MS/MS analysis. Genotoxic potential of NMUr was assessed employing a flow-cytometry based in vitro mutagenesis assay in the phosphatidylinositol-glycan biosynthesis class-A (PIG-A) gene. A wide distribution of responses to NMUr was observed with no correlation to gender or ethnicity. While the rate of O 6-mG repair partially influenced the toxicity of NMUr, it did not appear to be the major factor affecting individual susceptibility to the mutagenic effects of NMUr. Genome-wide analysis identified several novel single nucleotide polymorphisms to be explored in future functional validation studies for a number of the toxicological end points.