Complete Genome Sequence of Herpes Simplex Virus 1 Strain McKrae

Jiao, Xiaoli; Sui, Hongyan; Lyons, Christopher J.; Tran, Bao; Sherman, Brad T.; Imamichi, Tomozumi

doi:10.1128/mra.00993-19

Cited by 12 publications

(8 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…To demonstrate a profile of DNA virus‐dependent acetylation on Ku70 and a correlation between the acetylation and the IFN‐λ1 induction may delineate the mechanism of the viral strain‐dependent immune response. To precisely define the mechanism underlying the strain dependency in the IFN induction and Ku70 translocation, we recently completed full‐length viral DNA sequences of two strains 59,60 and a comparative study is currently underway. Deschamps and Kalamyoki reported that HSV‐1 strain 17 UL46 suppresses STING‐mediated IFN‐β and ISG expression in HEL cells, a human erythroleukaemia cell line 61 .…”

Section: Discussionmentioning

confidence: 99%

Cytoplasmic‐translocated Ku70 senses intracellular DNA and mediates interferon‐lambda1 induction

2021

Self Cite

View full text Add to dashboard Cite

We have previously identified that human Ku70, a nuclear protein, serves as a cytosolic DNA sensor. Upon transfection with DNA or infection with DNA virus, Ku70 translocates from the nucleus into the cytoplasm and then predominately induces interferon lambda1 (IFN-k1) rather than IFN-alpha or IFN-beta, through a STING-dependent signalling pathway. However, a detailed mechanism for Ku70 cytoplasmic translocation and its correlation with IFN-k1 induction have not been fully elucidated. Here, we observed that cytoplasmic translocation of Ku70 only occurred in DNA-triggered IFN-k1-inducible cells. Additionally, infection by Herpes simplex virus type-1 (HSV-1), a DNA virus, induces cytoplasmic translocation of Ku70 and IFN-k1 induction in a strain-dependent manner: the translocation and IFN-k1 induction were detected upon infection by HSV-1 McKrae, but not MacIntyre, strain. A kinetic analysis indicated that cytoplasmic translocation of Ku70 was initiated right after DNA transfection and was peaked at 6 hr after DNA stimulation. Furthermore, treatment with leptomycin B, a nuclear export inhibitor, inhibited both Ku70 translocation and IFN-k1 induction, suggesting that Ku70 translocation is an essential and early event for its cytosolic DNA sensing. We further confirmed that enhancing the acetylation status of the cells promotes Ku70's cytoplasmic accumulation, and therefore increases DNA-mediated IFN-k1 induction. These findings provide insights into the molecular mechanism by which the versatile sensor detects pathogenic DNA in a localization-dependent manner.

show abstract

Section: Discussionmentioning

confidence: 99%

Cytoplasmic‐translocated Ku70 senses intracellular DNA and mediates interferon‐lambda1 induction

2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Thus, we analyzed the whole genomes of wild-type (WT) HSV-1 and rHSV-1 by WGS. As previously shown, WGS and assembly of HSV-1 is highly challenging due to high GC content and multiple repeat sequences 19 . To this end, Sanger sequences were used in combination with Illumina short reads.…”

Section: Resultsmentioning

confidence: 99%

A novel bioluminescent herpes simplex virus 1 for in vivo monitoring of herpes simplex encephalitis

Uyar

Plante

Piret

et al. 2021

Sci Rep

View full text Add to dashboard Cite

Herpes simplex virus 1 (HSV-1) is responsible for herpes simplex virus encephalitis (HSE), associated with a 70% mortality rate in the absence of treatment. Despite intravenous treatment with acyclovir, mortality remains significant, highlighting the need for new anti-herpetic agents. Herein, we describe a novel neurovirulent recombinant HSV-1 (rHSV-1), expressing the fluorescent tdTomato and Gaussia luciferase (Gluc) enzyme, generated by the Clustered regularly interspaced short palindromic repeats (CRISPR)—CRISPR-associated protein 9 (Cas9) (CRISPR-Cas9) system. The Gluc activity measured in the cell culture supernatant was correlated (P = 0.0001) with infectious particles, allowing in vitro monitoring of viral replication kinetics. A significant correlation was also found between brain viral titers and Gluc activity in plasma (R2 = 0.8510, P < 0.0001) collected from BALB/c mice infected intranasally with rHSV-1. Furthermore, evaluation of valacyclovir (VACV) treatment of HSE could also be performed by analyzing Gluc activity in mouse plasma samples. Finally, it was also possible to study rHSV-1 dissemination and additionally to estimate brain viral titers by in vivo imaging system (IVIS). The new rHSV-1 with reporter proteins is not only as a powerful tool for in vitro and in vivo antiviral screening, but can also be used for studying different aspects of HSE pathogenesis.

show abstract

“…Acyclovir was the first highly virus-selective antiviral drug. It serves as a more preferential substrate for the HSV-encoded thymidine-kinase than host cell kinases for its initial phosphorylation (Frobert et al , 2005; Jiao et al , 2019). Previously, 3′-azido-2′,3′-unsaturated thymine analogue has shown better activity compared to other nucleoside analogues against SARS-CoV (EC50=10.3 µM) with a significant level of toxicity (Chu et al , 2006).…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 has observably higher propensity to accept uracil as nucleotide substitution: Prevalence of amino acid substitutions and their predicted functional implications in circulating SARS-CoV-2 in India up to July, 2020

Roy

Nath

Mallick

et al. 2020

Preprint

View full text Add to dashboard Cite

SARS-CoV-2 has emerged as pandemic all over the world since late 2019. In this study, we investigated the diversity of the virus in the context of SARS-CoV-2 spread in India. Full-length SARS-CoV-2 genome sequences of the circulating viruses from all over India were collected from GISAID, an open data repository, until 25thJuly, 2020. We have focused on the non-synonymous changes across the genome that resulted in amino acid substitutions. Analysis of the genomic signatures of the non-synonymous mutations demonstrated a strong association between the time of sample collection and the accumulation of genetic diversity. Most of these isolates from India belonged to the A2a clade (63.4%) which has overcome the selective pressure and is spreading rapidly across several continents. Interestingly a new clade I/A3i has emerged as the second-highest prevalent type among the Indian isolates, comprising 25.5% of the Indian sequences. Emergence of new mutations in the S protein was observed. Major SARS-CoV-2 clades in India have defining mutations in the RdRp. Maximum accumulation of mutations was observed in ORF1a.Other than the clade-defining mutations, few representative non-synonymous mutations were checked against the available crystal structures of the SARS-CoV-2 proteins in the DynaMut server to assess their thermodynamic stability. We have observed that SARS-CoV-2 genomes contain more uracil than any other nucleotide. Furthermore, substitution of nucleotides to uracil was highest among the non-synonymous mutations observed. The A+U content in SARS-CoV-2 genome is much higher compared to other RNA viruses, suggesting that the virus RdRp has a propensity towards uracil incorporation in the genome. This implies that thymidine analogues may have a better chance to competitively inhibit SARS-CoV-2 RNA replication than other nucleotide analogues.

show abstract

Complete Genome Sequence of Herpes Simplex Virus 1 Strain McKrae

Cited by 12 publications

References 17 publications

Cytoplasmic‐translocated Ku70 senses intracellular DNA and mediates interferon‐lambda1 induction

Cytoplasmic‐translocated Ku70 senses intracellular DNA and mediates interferon‐lambda1 induction

A novel bioluminescent herpes simplex virus 1 for in vivo monitoring of herpes simplex encephalitis

SARS-CoV-2 has observably higher propensity to accept uracil as nucleotide substitution: Prevalence of amino acid substitutions and their predicted functional implications in circulating SARS-CoV-2 in India up to July, 2020

Contact Info

Product

Resources

About