Comparative Genomic Sequencing and Pathogenic Properties of Equine Herpesvirus 1 KyA and RacL11.
Abstract: Equine herpesvirus 1 (EHV-1) is a major pathogen affecting equines worldwide. The virus causes respiratory disease, abortion, and, in some cases, neurological disease. EHV-1 Kentucky A (KyA) is attenuated in the mouse and equine, whereas wild-type pathogenic strain RacL11 induces severe inflammatory infiltration of the lung, causing infected mice to succumb. The complete DNA sequencing of the KyA genome revealed that genes UL17 (ORF17), US6 (ORF73; gI), US7 (ORF74; gE), and US8 (ORF75; 10 K) are deleted as compared to the RacL11 and Ab4 genomes. In-frame deletions in the US1 (ORF68), US4 (ORF71; gp2), and UL63 (ORF63; EICP0) genes and point mutations in 14 different open reading frames (ORFs) were detected in the KyA genome. Interestingly, UL1 (ORF1) and UL2 (ORF2) were deleted in both KyA and RacL11. Our previous studies showed that EHV-1 glycoproteins gI, gE, and full-length gp2 contribute to the pathogenesis of the RacL11 strain. The confirmation of these gene deletions in KyA suggests their contribution to the attenuation of this virus. The growth kinetics results revealed that KyA replicates to high titers in cell culture as compared to RacL11 and Ab4, indicating that the above genomic deletions and mutations in KyA do not have an inhibitory effect on KyA replication in cells of mouse, rabbit, equine, or human origin. Studies of EHV-1 pathogenesis in CBA mice showed that KyA is attenuated whereas mice infected with RacL11 succumbed by 3-6 days post-infection, which is consistent with our previous results.
Publication Date: 2017-12-11 PubMed ID: 29312962PubMed Central: PMC5732242DOI: 10.3389/fvets.2017.00211Google Scholar: Lookup
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Summary
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This research study examined the genetic makeup and pathogenic properties of the Equine Herpesvirus (EHV-1) strains — Kentucky A (KyA) and RacL11. The study established that the KyA strain, while capable of efficient replication in cells, tends to be less severe compared to the RacL11 strain due to gene deletions and mutations.
Genomic Comparison of EHV-1 Strains
- The researchers conducted full genomic sequencing of the EHV-1 strains: KyA and RacL11.
- They discovered than the KyA genome has deletions in genes UL17, US6, US7, and US8, compared to the RacL11 and Ab4 genomes.
- There were in-frame deletions spotted in genes US1, US4, and UL63, and point mutations in 14 various open reading frames in the KyA genome.
- Both KyA and RacL11 genomes showed deletions in genes UL1 and UL2.
Role of Deletions and Mutations in Pathogenicity
- EHV-1 glycoproteins gI, gE, and full-length gp2 play a distinct role in how the RacL11 strain causes disease.
- The deleted genes in the KyA strain are believed to contribute to its attenuation, or reduced severity, compared to other strains.
Viral Growth Kinetics
- Despite its genomic deletions and mutations, the KyA strain showed competency to reproduce to high levels in cell culture compared to RacL11 and Ab4.
- These genomic changes in KyA do not have an inhibitory effect on the strain’s replication in cells from mice, rabbits, horses, or humans.
Pathogenesis Studies
- The research confirmed that KyA is attenuated when studied in CBA mice, whereas those infected with RacL11 succumbed within 3-6 days post-infection.
- This result aligns with prior research findings, suggesting a consistent behavior on the part of the RacL11 strain.
In summary, the research underscores genetic differences between EHV-1 strains and their impact on disease severity, providing insights on the pathogenesis of this virus in different hosts. It could be beneficial towards developing strategies for disease prevention and treatment.
Cite This Article
APA
Shakya AK, O'Callaghan DJ, Kim SK.
(2017).
Comparative Genomic Sequencing and Pathogenic Properties of Equine Herpesvirus 1 KyA and RacL11.
Front Vet Sci, 4, 211.
https://doi.org/10.3389/fvets.2017.00211 Publication
Researcher Affiliations
- Department of Microbiology and Immunology, Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, LA, United States.
- Department of Microbiology and Immunology, Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, LA, United States.
- Department of Microbiology and Immunology, Center for Molecular and Tumor Virology, Louisiana State University Health Sciences Center, Shreveport, LA, United States.
Grant Funding
- P30 GM110703 / NIGMS NIH HHS
- R01 AI022001 / NIAID NIH HHS
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