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Dissecting Host-virus Interaction in Lytic Replication of a Model Herpesvirus
Published on: October 7, 2011
Sequence and comparative analysis of the genome of HSV-1 strain McKrae
1Department of Biomedical Sciences, College of Veterinary Medicine, Oregon State University, Corvallis, OR 97331, USA.
Abstract:
Ocular infection by HSV-1 strain McKrae is neurovirulent in both mice and rabbits and causes fatal encephalitis in approximately 50% of animals. In addition, it spontaneously reactivates with high frequency relative to other HSV-1 strains in rabbits. We sequenced the McKrae strain genome and compared its coding protein sequences with those of six other HSV-1 strains. Most of the 74 predicted protein sequences are conserved; only eleven are less than 98% conserved. Eight proteins were identified to be unique for McKrae based on sequence homology bit score ratio (BSR). These include five proteins showing significant variations (RL1, RS1, UL49A, US7 and US11), two truncated proteins (UL36 and UL56) and one (US10) containing an extended open reading frame. The McKrae strain also has unique features in its 'a' sequence and non-coding sequences, such as LAT and miRNA. These data are indicative of strain variation but need further work to connect observed differences with phenotype effects.
Insights
The McKrae strain of herpes simplex virus type 1 (HSV-1) exhibits unique genetic variations, including distinct proteins and non-coding sequences, potentially explaining its high neurovirulence and reactivation frequency in animal models.
Area of Science:
- Virology
- Genomics
- Neuroscience
Background:
- Herpes simplex virus type 1 (HSV-1) strain McKrae is known for its neurovirulence and high spontaneous reactivation frequency in rabbits.
- Understanding the genetic basis of these phenotypic traits is crucial for comprehending HSV-1 pathogenesis.
Purpose of the Study:
- To sequence the genome of the HSV-1 McKrae strain.
- To compare its protein-coding sequences with other HSV-1 strains to identify unique genetic features.
- To investigate potential genetic correlates of the McKrae strain's observed neurovirulence and reactivation phenotype.
Main Methods:
- Whole-genome sequencing of the HSV-1 McKrae strain.
- Comparative genomic analysis of coding protein sequences against six other HSV-1 strains.
- Identification of unique and significantly varied proteins using sequence homology bit score ratio (BSR).
Main Results:
- The McKrae strain genome was sequenced, revealing 74 predicted protein sequences.
- Eleven proteins showed less than 98% conservation compared to other strains.
- Eight proteins were identified as unique to McKrae, including five with significant variations (RL1, RS1, UL49A, US7, US11), two truncated proteins (UL36, UL56), and one with an extended open reading frame (US10).
- Unique features were also noted in non-coding regions, including the 'a' sequence, latency-associated transcript (LAT), and microRNA (miRNA).
Conclusions:
- The HSV-1 McKrae strain possesses unique genetic characteristics, including distinct protein sequences and variations in non-coding regions.
- These genetic differences may contribute to its heightened neurovirulence and reactivation potential.
- Further research is warranted to establish a direct correlation between these identified genetic variations and the observed phenotypic effects.
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