Genomic analysis for virulence determinants in feline herpesvirus type-1 isolates
Feline herpesvirus type 1 (FHV-1) is a widespread cause of respiratory and ocular disease in domestic cats. A spectrum of disease severity is observed in host animals, but there has been limited prior investigation into viral genome factors which could be responsible. Stocks of FHV-1 were established from oropharyngeal swabs obtained from twenty-five cats with signs of infection housed in eight animal shelters around the USA. A standardized numerical host clinical disease severity scoring scheme was used for each cat from which an isolate was obtained. Illumina MiSeq was used to sequence the genome of each isolate. Genomic homogeneity among isolates was relatively high. A general linear model for fixed effects determined that only two synonymous single nucleotide polymorphisms across two genes (UL37/39) in the same isolate (from one host animal with a low disease severity score) were significantly associated (p ≤ 0.05) with assigned host respiratory and total disease severity score. No variants in any isolate were found to be significantly associated with assigned host ocular disease severity score. A concurrent analysis of missense mutations among the viral isolates identified three genes as being primarily involved in the observed genomic variation, but none were significantly associated with host disease severity scores. An ancestral state likelihood reconstruction was performed and determined that there was no evidence of a connection between host disease severity score and viral evolutionary state. We conclude from our results that the spectrum of host disease severity observed with FHV-1 is unlikely to be primarily related to viral genomic variations, and is instead due to host response and/or other factors.
KeywordsFeline herpesvirus Virulence Herpes Host response Disease severity Cat
The authors would like to thank Dr. Curtis Brandt, Aaron Kolb, Dr. Kristen Bernard, Dr. Sandra Newbury and the University of Wisconsin-Madison Biotechnology Center for their assistance and advice in obtaining samples, viral isolation and sequencing. The authors would also like to thank Kristen Cooley CVT, Dr. McLean Gunderson, Jenni Rose McKay, Dr. Aleisha Swartz, Dr. Sharon Ostermann, Dr. Sarah Frei, Dr. Christine Solis, Dr. Julie Andersen, Dr. Emily Purvis, Dr. Margaret Wixson, Dr. Lauren Park, Dr. Cooper Brookshire, Dr. Mark Verdino, Dr. Hillary Herendeen, Dr. Jen Dalmasso, Dr. Libby Gutting and Dr. Kimberly Woodruff for their assistance in acquiring the samples from the cats in this study. Finally the authors would like to thank the LSU Center for Computation and Technology and High-Performance Computing Clusters for computational resources and support.
AL: Designed study, performed sample collection and preparation for sequencing, wrote manuscript. LC: Analyzed data, wrote manuscript. GM: Designed study, reviewed manuscript. EB: Designed study, reviewed manuscript. KK: Reviewed manuscript.
This project was partially funded by a Grant from the University of Wisconsin-Madison Veterinary Teaching Hospital Companion Animal Fund; NIH Vision Research Core Grant, P30EY016665, and NIH National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000427. This work was also supported by an unrestricted Grant from Research to Prevent Blindness, Inc. to the Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
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Conflict of interest
None of the authors have any conflict of interest to report in regards to this manuscript.
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