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...

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Bibliographic Details
Published in:	PLoS pathogens Vol. 7; no. 10; p. e1002282
Main Authors:	Szpara, Moriah L, Tafuri, Yolanda R, Parsons, Lance, Shamim, S Rafi, Verstrepen, Kevin J, Legendre, Matthieu, Enquist, L W
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 01-10-2011 Public Library of Science (PLoS)
Subjects:	Acquisitions & mergers Alphaherpesvirinae - genetics Alphaherpesvirinae - metabolism Alphaherpesvirinae - pathogenicity Alphaherpesvirus Amino Acid Sequence Animal diseases Animals Base Sequence Binding sites Biology Deoxyribonucleic acid DNA Genetic Variation Genome, Viral Genomes Genomics Health aspects Herpes simplex virus 1 Herpesvirus Herpesvirus 1, Human - genetics Herpesvirus 1, Suid - genetics Herpesvirus 3, Human - genetics Herpesvirus Vaccines - genetics Herpesvirus Vaccines - immunology Herpesviruses Heterogeneity HIV Human immunodeficiency virus Human populations Humans Infections Livestock Medicine Microsatellite Repeats Molecular Sequence Data Mortality Mutation Nucleic acids Phenotypic variations Physiological aspects Polymorphism, Genetic Population Protein folding Pseudorabies Vaccines - genetics Pseudorabies virus Sequence Alignment Sequence Analysis, DNA Vaccines Varicella-zoster virus Veterinary Science Viral proteins Viral Proteins - genetics Viruses United States
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Article-2 ObjectType-Feature-1 Conceived and designed the experiments: MLS YRT LP SRS KJV ML LWE. Performed the experiments: MLS YRT LP SRS ML. Analyzed the data: MLS YRT LP SRS ML. Contributed reagents/materials/analysis tools: MLS YRT LP SRS KJV ML LWE. Wrote the paper: MLS YRT KJV ML LWE.
ISSN:	1553-7374 1553-7366 1553-7374
DOI:	10.1371/journal.ppat.1002282