This dissertation describes the molecular and immunological characterization of the UHB flanked genes among isolates and species of B. burgdorferi sensu lato complex. OspE and ospF, the first UHB ...flanked genes to be identified, encode immunogenic surface exposed lipoproteins. It was postulated that these proteins may be useful in the development of Lyme disease vaccines or diagnostic assays. To assess their utility for these applications we began an analysis of these genes in a diverse group of Borrelia isolates. Hybridization analyses revealed that the sequence upstream of ospEF operon is multi-copy. Sequence analyses revealed that this multi-copy sequence is highly conserved and flanks a variable group of lipoprotein. We refer this conserved sequence as the upstream homology box (UHB) or UHB element. The variable nature of the UHB flanked coding sequences suggested that these genes are not evolutionarily stable. Polymorphisms are primarily in the form of insertions and deletions and cluster in two distinct domains (variable domain 1 and 2) which in some cases are flanked by direct repeat elements. Computer analyses predict the variable domain 1 to be hydrophilic, surface exposed, and antigenic suggesting that recombination and or mutation in this domain could lead to the generation of new antigenic variants that could play a role in immune evasion. Using an isogeneic clone of Borrelia burgdorferi B31G (designated B31Gc1) and the murine model for Lyme disease we demonstrate that the ospE-related genes undergo mutation and rearrangement during infection in mice. The mutations that develop during infection resulted in the generation of OspE proteins with altered antigenic characteristics. In conclusion, this analyses suggest that the UHB gene family is not evolutionarily stable and that the polymorphic ospE alleles has been modified through mutation or recombination events. Collectively, this study strong indicated that the continue change of the OspE antigen through mutations and/or rearrangements could play an important role in antigenic variation after infection in mammals.
Cancer-Host Interactions Chung, Leland W. K.; Huang, Wen-Chin; Sung, Shian-Ying ...
Prostate Cancer
Book Chapter
Cancer is not a single cell disease and its existence and behavior are constantly modulated by the host. Cancer gene expression and genetics are also highly dynamic and are regulated epigenetically ...by the host. In this chapter, we describe the molecular pathways leading to an unusual property of cancer cells: the ability to mimic the host microenvironment, and, in particular, the characteristics of osteomimicry and vasculogenic mimicry. We also discuss the importance of host inflammatory and stem cells, which contribute to the growth and survival of cancer cells. By understanding the salient features of cancer-host interaction, novel therapeutics may be developed to target both cancer and host in the treatment of lethal prostate cancer metastases.
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