A Wide Extent of Inter-Strain Diversity in Virulent and Vaccine Strains of Alphaherpesviruses

Alphaherpesviruses are widespread in the human population, and include herpes simplex virus 1 (HSV-1) and 2, and varicella zoster virus (VZV). These viral pathogens cause epithelial lesions, and then infect the nervous system to cause lifelong latency, reactivation, and spread. A related veterinary herpesvirus, pseudorabies (PRV), causes similar disease in livestock that result in significant economic losses. Vaccines developed for VZV and PRV serve as useful models for the development of an HSV-1 vaccine. We present full genome sequence comparisons of the PRV vaccine strain Bartha, and two virulent PRV isolates, Kaplan and Becker. These genome sequences were determined by high-throughput sequencing and assembly, and present new insights into the attenuation of a mammalian alphaherpesvirus vaccine strain. We find many previously unknown coding differences between PRV Bartha and the virulent strains, including changes to the fusion proteins gH and gB, and over forty other viral proteins. Inter-strain variation in PRV protein sequences is much closer to levels previously observed for HSV-1 than for the highly stable VZV proteome. Almost 20% of the PRV genome contains tandem short sequence repeats (SSRs), a class of nucleic acids motifs whose length-variation has been associated with changes in DNA binding site efficiency, transcriptional regulation, and protein interactions. We find SSRs throughout the herpesvirus family, and provide the first global characterization of SSRs in viruses, both within and between strains. We find SSR length variation between different isolates of PRV and HSV-1, which may provide a new mechanism for phenotypic variation between strains. Finally, we detected a small number of polymorphic bases within each plaque-purified PRV strain, and we characterize the effect of passage and plaque-purification on these polymorphisms. These data add to growing evidence that even plaque-purified stocks of stable DNA viruses exhibit limited sequence heterogeneity, which likely seeds future strain evolution

Doctor of Philosophy

thesisThe Ut0-Aztecan Family is a distinguished one and contains members that are culturally as diverse as the Maya and the "Digger Indians" of Nevada. It is similarities in language and not in culture traits that cause anthropologists to classify Indian tribes in families, and then to divide these large families into branches in which the tribal tongue is still more similar

American West Center occasional paper number 6: An essay on the historiography of the Indians of the Americas

Bibliography of sources and works relating to the portrayal of the American Indian, along with an essay on government documents and archives by C. B. Clark and a discussion of the Human Relations Area Files by Dennis R. Defa. The sixth Occasional paper of the University of Utah's American West Cente

Ute Women's Conference (3/17/67)

UteRecorded by S. Lyman Tyler and J. Witherspoon in Salt Lake City, Utah on 17 March 1967. Includes speeches by Currey, Couch, Noble, and McKinley in Ute and English. Not transcribed. Dorisduke 1436.pd

American West Center occasional paper number 17: Spanish laws concerning discoveries, pacifications and settlements among the Indians

The 17th Occasional paper of the University of Utah's American West Center, including an introduction, the first English translation of the New Ordinances of Philip II, July 1573, and of Book IV from the Recopiacion de leyes de los Reinos de las Indias relating to the Native Americans

American West Center occasional paper number 25: Historiography of Utah, the Mormons, and the West, a personal approach

The 25th Occasional paper of the University of Utah's American West Center, including an essay on writing about Mormons in the West, entries on Mormonism, the Mormons, and Utah as listed in Sabin, and writings since the publication of Chad Flake's Mormon Bibliography, 1830-1930

American West Center occasional paper number 24: European-American relations with the indigenous Americans: Crown to Congress to Executive, and colony to state

The 24th Occasional paper of the University of Utah's American West Center, an essay on government regulation of the status of Native Americans, especially in the United States. Includes a reproduction of a lengthy section of the 18th annual report of the Bureau of American Ethnology (1899) on the control of relations with the Indians by individual American colonies