Genetic variability in the region encompassing reiteration VII of herpes simplex virus type 1, including deletions and multiplications related to recombination between direct repeats

Umene, Kenichi; Yoshida, Masami; Fukumaki, Yasuyuki

doi:10.1186/s40064-015-0990-y

Cited by 4 publications

(4 citation statements)

References 46 publications

(97 reference statements)

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“…The high sequence identity across each set of repeats indicates that reads derived from these repeat regions are ambiguous with respect to which repeat they arise from and therefore cannot be mapped to a unique position. The high degree of sequence identity between the two copies of each repeat suggests recombination between these regions during HSV1 replication [ 36 , 37 ]. The existence of these repeats generates additional difficulties in genomic analyses, even by Southern blot, as HSV1 stocks consist of equal fractions of four different isomers of the genome, which differ in the relative position and orientation of the RS–US–RS segments, which can be on either the left or right side of the genome relative to the RL–UL–RL segments ( Figure 2 ) [ 38 ].…”

Section: Resultsmentioning

confidence: 99%

Reliable Detection of Herpes Simplex Virus Sequence Variation by High-Throughput Resequencing

Morse

Calabro

Fear

et al. 2017

Viruses

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High-throughput sequencing (HTS) has resulted in data for a number of herpes simplex virus (HSV) laboratory strains and clinical isolates. The knowledge of these sequences has been critical for investigating viral pathogenicity. However, the assembly of complete herpesviral genomes, including HSV, is complicated due to the existence of large repeat regions and arrays of smaller reiterated sequences that are commonly found in these genomes. In addition, the inherent genetic variation in populations of isolates for viruses and other microorganisms presents an additional challenge to many existing HTS sequence assembly pipelines. Here, we evaluate two approaches for the identification of genetic variants in HSV1 strains using Illumina short read sequencing data. The first, a reference-based approach, identifies variants from reads aligned to a reference sequence and the second, a de novo assembly approach, identifies variants from reads aligned to de novo assembled consensus sequences. Of critical importance for both approaches is the reduction in the number of low complexity regions through the construction of a non-redundant reference genome. We compared variants identified in the two methods. Our results indicate that approximately 85% of variants are identified regardless of the approach. The reference-based approach to variant discovery captures an additional 15% representing variants divergent from the HSV1 reference possibly due to viral passage. Reference-based approaches are significantly less labor-intensive and identify variants across the genome where de novo assembly-based approaches are limited to regions where contigs have been successfully assembled. In addition, regions of poor quality assembly can lead to false variant identification in de novo consensus sequences. For viruses with a well-assembled reference genome, a reference-based approach is recommended.

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Section: Resultsmentioning

confidence: 99%

Reliable Detection of Herpes Simplex Virus Sequence Variation by High-Throughput Resequencing

Morse

Calabro

Fear

et al. 2017

Viruses

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“…While US11 is a nonessential gene and while there is clear evidence for its strainto-strain diversity (57,(75)(76)(77), the ORF was found to be preserved in all HSV-1 strains that have been sequenced. These findings imply that although US11 variants arise, there is significant selective pressure to retain US11 function.…”

Section: Discussionmentioning

confidence: 99%

The US11 Gene of Herpes Simplex Virus 1 Promotes Neuroinvasion and Periocular Replication following Corneal Infection

Charron

Ward

North

et al. 2019

J Virol

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Herpes simplex virus 1 (HSV-1) cycles between phases of latency in sensory neurons and replication in mucosal sites. HSV-1 encodes two key proteins that antagonize the shutdown of host translation, US11 through preventing PKR activation and ICP34.5 through mediating dephosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α). While profound attenuation of ICP34.5 deletion mutants has been repeatedly demonstrated, a role for US11 in HSV-1 pathogenesis remains unclear. We therefore generated an HSV-1 strain 17 US11-null virus and examined its properties in vitro and in vivo. In U373 glioblastoma cells, US11 cooperated with ICP34.5 to prevent eIF2α phosphorylation late in infection. However, the effect was muted in human corneal epithelial cells (HCLEs), which did not accumulate phosphorylated eIF2α unless both US11 and ICP34.5 were absent. Low levels of phosphorylated eIF2α correlated with continued protein synthesis and with the ability of virus lacking US11 to overcome antiviral immunity in HCLE and U373 cells. Neurovirulence following intracerebral inoculation of mice was not affected by the deletion of US11. In contrast, the time to endpoint criteria following corneal infection was greater for the US11-null virus than for the wild-type virus. Replication in trigeminal ganglia and periocular tissue was promoted by US11, as was periocular disease. The establishment of latency and the frequency of virus reactivation from trigeminal ganglia were unaffected by US11 deletion, although emergence of the US11-null virus occurred with slowed kinetics. Considered together, the data indicate that US11 facilitates the countering of antiviral response of infected cells and promotes the efficient emergence of virus following reactivation. IMPORTANCE Alphaherpesviruses are ubiquitous DNA viruses and include the human pathogens herpes simplex virus 1 (HSV-1) and HSV-2 and are significant causes of ulcerative mucosal sores, infectious blindness, encephalitis, and devastating neonatal disease. Successful primary infection and persistent coexistence with host immune defenses are dependent on the ability of these viruses to counter the antiviral response. HSV-1 and HSV-2 and other primate viruses within the Simplexvirus genus encode US11, an immune antagonist that promotes virus production by preventing shutdown of protein translation. Here we investigated the impact of US11 deletion on HSV-1 growth in vitro and pathogenesis in vivo. This work supports a role for US11 in pathogenesis and emergence from latency, elucidating immunomodulation by this medically important cohort of viruses.

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“…Clinical data suggests an increasing number of genital infections caused by HSV − 1, although HSV − 2 is a predominate agent [5]. The virus is capable of causing recurrent infections in the host due to its ability to go into a latency state [4,6,7,8]. HSV also responsible for neonatal herpes infections, genital ulcer disease and increases the acquisition of other sexually transmitted infections such as Human Immunode ciency Virus (HIV) and Human Papillomavirus (HPV) [1,3].…”

Section: Introductionmentioning

confidence: 99%

Herpes Simplex Virus Gene Variants among Asymptomatic Women in Ghana: a pilot study

Debrah

Harry

Ama

et al. 2022

Preprint

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Herpes simplex virus infections account for a large burden of disease worldwide. HSV-1 is traditionally considered to cause orofacial infections, whereas HSV-2 is known for genital infections. A number of studies have suggested an increase of genital herpes infections caused by HSV-1. As reporting of diseases caused by herpes simplex virus is not mandatory in Ghana, reliable statistics on the epidemiology of infections are not available. We took advantage of the Cervicare program in Ghana to screen for the presence of HSV variants 1 and 2 among a convenient subset of asymptomatic women presenting for cervical screening in Accra, Ghana (n = 94). Genetic markers for both HSV 1 and 2 were detected in cervical swabs. There was a preponderance of HSV-1 (12.8%) genital infections in our study sample: compared to HSV-2 (4.8%). HSV-1 and 2 co-infection was detected in 4.3% of study population. Among positive cases for HSV-1 DNA, 92% had confirmed seropositive HSV-1 status and 8% were borderline result. All positive HSV-2 DNA were confirmed seropositive HSV-2 status. We have successfully demonstrated the presence of herpes simplex virus type 1 and type 2 gene variants in genital swabs. Owing to the lack of epidemiological data on genital HSV-1 infection in Ghana, the role of sexual transmission for HSV-1 is unclear: the findings of our pilot study have important public health implications. A bigger surveillance study is recommended in Ghana to identify the etiology of genital herpes and estimate the true burden of asymptomatic herpes infection in the population.

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Genetic variability in the region encompassing reiteration VII of herpes simplex virus type 1, including deletions and multiplications related to recombination between direct repeats

Cited by 4 publications

References 46 publications

Reliable Detection of Herpes Simplex Virus Sequence Variation by High-Throughput Resequencing

Reliable Detection of Herpes Simplex Virus Sequence Variation by High-Throughput Resequencing

The US11 Gene of Herpes Simplex Virus 1 Promotes Neuroinvasion and Periocular Replication following Corneal Infection

Herpes Simplex Virus Gene Variants among Asymptomatic Women in Ghana: a pilot study

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