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Viet Chau, Aaron Kolb, Darlene Miller, Curtis R Brandt, Nicolas Yannuzzi; Phylogenic and Genomic Analysis of HSV-1 Ocular Isolates Recovered From Keratoconjunctivitis. Invest. Ophthalmol. Vis. Sci. 2022;63(7):497 – A0074.
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© ARVO (1962-2015); The Authors (2016-present)
There is limited data on the prevalence and genetic diversity of the herpes simplex virus type 1 (HSV-1) virulence genes in ocular isolates. Phylogenetic and genomic analyses of 9 HSV-1 conjunctival isolates were performed to help better understand genetic variability amongst common virulence genes in ocular herpetic disease.
Whole genome sequencing of 9 HSV-1 isolates recovered in tissue culture from conjunctival scrapings collected between 2004 and 2015 from patients with viral kerato-conjunctivitis were screened using the PacBio Sequel II platform. A phylogenetic network was generated using a multiple sequence alignment method, combining the 9 viral isolate sequences along with 160 global HSV-1 sequences. Protein sequence analyses of common virulence genes (thymidine kinase [TK], DNA polymerase, and ICP22) were performed.
Of the 9 samples, 8 mapped to the American-European clade, whereas the remaining one, closely aligned with the African clade. Both TK and DNA polymerase protein sequencing analyses revealed multiple single nucleotide polymorphisms (SNPs). The majority of these have been previously described, none however are known to confer antiviral resistance. One novel TK SNP (P300S) was found in two viral isolates and the potential effect of the polymorphism on TK and antiviral resistance has yet to be determined. Two novel DNA polymerase SNPs (T929A and R1001Q) were found, which have yet to be described in the literature. The impact on DNA polymerase and acyclovir susceptibility is also unknown. Analysis of ICP22 protein sequences did not reveal any novel protein coding SNPs, however two isolates contained an A78D change, which may affect nucleotidylation of the ICP22 protein.
Whole genome sequencing along with phylogenetic and genomic analyses are powerful tools for understanding genetic variability amongst ocular conjunctival HSV isolates. Identification of novel and common recurrent polymorphisms may help understand drivers of herpetic pathogenicity and factors that may influence virulence in ocular disease.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.
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