Regulation of AURKC expression by CpG island methylation in human cancer cells.

AURKC, a member of the Aurora kinase gene family, is highly expressed in testis but is either moderately expressed or repressed in most somatic cells. Varying expression of AURKC has been observed in human cancers, but the underlying mechanisms of differential expression have been investigated only to a limited extent. We investigated the role of promoter CpG methylation in the regulation of AURKC gene expression in human cancer cells, in relation to a recently reported AURKC transcription repressor PLZF/ZBTB16, implicated in transformation and tumorigenesis. AURKC and PLZF/ZBTB16 expression profiles were investigated in reference to CpG methylation status on the AURKC promoter experimentally, and also in The Cancer Genome Atlas (TCGA) dataset involving multiple cancer types. AURKC promoter showed dense to moderate hypermethylation correlating with low to moderate expression of the gene in normal somatic cells and cancer cell lines, while testis with high expression revealed marked hypo-methylation. Treatment with the demethylating agent, 5-aza-dC, but not the histone deacetylase (HDAC) inhibitor, TSA, led to elevated expression in cancer cell lines, indicating that promoter DNA methylation negatively regulates AURKC expression. High expression of PLZF in PLZF-transfected cells treated with 5-aza-dC only partially repressed expression of AURKC despite 5-aza-dC also inducing elevated PLZF expression. Analyses of the TCGA data showed differential expression of AURKC in multiple cancer types and stronger correlation of AURKC expression with CpG methylation compared to PLZF levels. These findings demonstrate that differential promoter CpG methylation is an important mechanism regulating AURKC expression in cancer cells.

Emerging tick-borne disease in African vipers caused by a Cowdria-like organism.

Heartwater is a tick-borne infectious disease caused by the rickettsial organism Cowdria ruminantium, currently Ehrlichia ruminantium. It poses an imminent threat to the Western Hemisphere, where it could cause mortality in cattle and other ruminant livestock in excess of 70%. It has been reported in the Caribbean; and its vector, Amblyomma sparsum, has been found on imported African spurred tortoises (Geochelone sulcata) and leopard tortoises (Geochelone pardalis) in southern Florida in the United States, leading to an importation ban on these reptiles. Symptoms have not been previously reported in reptiles. Here, we report peracute and acute deaths in African vipers imported from Africa through Florida. Signs included vomiting mucoid fluid, diarrhea, emaciation, convulsions, and death. Postmortem showed few gross lesions. The most consistent peracute and acute lesions were the pulmonary lesions and pericarditis with considerable bloody fluid in the pericardial sac (hydropericardium). These lesions strongly resembled the lesions of heartwater and a coccobacillus of less than 1-micron diameter was isolated in viper cell culture. The outbreak was brought to a halt by tick control and treatment of all exposed snakes with tetracycline. This isolation, tetracycline sensitivity, clinical signs, preliminary results with polymerase chain reaction of pCS20 ORF, and the viper preference of the disease may indicate a Cowdria-related attenuated species that has adapted to infect reptiles or an emerging new form of this group of microbes.

Viral association with the elusive rickettsia of viper plague from Ghana, West Africa.

We previously reported a rickettsial heartwater-like disease in vipers from Ghana that resembled heartwater in its gross lesions, was apparently transmitted by ticks (Aponomma and Amblyomma), and responded clinically favorably to early treatment with tetracycline. Cell culture showed consistent cytopathic effects in bovine endothelial cells, viper cells, and mouse cells, and inhibition of cytopathic effect by tetracycline in vitro. A type D retrovirus was observed in vacuoles in all infected cells. The virus and rickettsia infection was associated with transfer of cytopathic effect, regardless of cell species. Close association of virus and rickettsia may indicate a dual infection etiology of viper plague.