scholarly journals Whole genome sequencing of Herpes Simplex Virus 1 directly from human cerebrospinal fluid reveals selective constraints in neurotropic viruses

2019 ◽  
Author(s):  
Florent Lassalle ◽  
Mathew A Beale ◽  
Tehmina Bharucha ◽  
Charlotte A Williams ◽  
Rachel J Williams ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Direct Sequencing ◽  
Clinical Manifestations ◽  
Skin Lesions ◽  
Target Enrichment ◽  
Mortality And Morbidity ◽  
Simplex Virus ◽  
Hsv 1

AbstractHerpes Simplex Virus type 1 (HSV-1) chronically infects over 70% of the global population. Clinical manifestations are largely restricted to recurrent epidermal vesicles. However, HSV-1 also leads to encephalitis, the infection of the brain parenchyma, with high associated rates of mortality and morbidity. In this study, we performed target enrichment followed by direct sequencing of HSV-1 genomes, using target enrichment methods on the cerebrospinal fluid (CSF) of clinical encephalitis patients and from skin swabs of epidermal vesicles on non-encephalopathic patients. Phylogenetic analysis revealed high inter-host diversity and little population structure. By contrast, samples from different lesions in the same patient clustered with similar patterns of allelic variants. Comparison of consensus genome sequences shows HSV-1 has been freely recombining, except for distinct islands of linkage disequilibrium (LD). This suggests functional constraints prevent recombination between certain genes, notably those encoding pairs of interacting proteins. Distinct LD patterns characterised subsets of viruses recovered from CSF and skin lesions, which may reflect different evolutionary constraints in different body compartments. Functions of genes under differential constraint related to immunity or tropism and provide new hypotheses on tissue-specific mechanisms of viral infection and latency.

scholarly journals Whole genome sequencing of Herpes Simplex Virus 1 directly from human cerebrospinal fluid reveals selective constraints in neurotropic viruses

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Florent Lassalle ◽  
Mathew A Beale ◽  
Tehmina Bharucha ◽  
Charlotte A Williams ◽  
Rachel J Williams ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Direct Sequencing ◽  
Clinical Manifestations ◽  
Skin Lesions ◽  
Target Enrichment ◽  
Mortality And Morbidity ◽  
Simplex Virus ◽  
Hsv 1

Abstract Herpes Simplex Virus type 1 (HSV-1) chronically infects over 70 per cent of the global population. Clinical manifestations are largely restricted to recurrent epidermal vesicles. However, HSV-1 also leads to encephalitis, the infection of the brain parenchyma, with high associated rates of mortality and morbidity. In this study, we performed target enrichment followed by direct sequencing of HSV-1 genomes, using target enrichment methods on the cerebrospinal fluid (CSF) of clinical encephalitis patients and from skin swabs of epidermal vesicles on non-encephalopathic patients. Phylogenetic analysis revealed high inter-host diversity and little population structure. In contrast, samples from different lesions in the same patient clustered with similar patterns of allelic variants. Comparison of consensus genome sequences shows HSV-1 has been freely recombining, except for distinct islands of linkage disequilibrium (LD). This suggests functional constraints prevent recombination between certain genes, notably those encoding pairs of interacting proteins. Distinct LD patterns characterised subsets of viruses recovered from CSF and skin lesions, which may reflect different evolutionary constraints in different body compartments. Functions of genes under differential constraint related to immunity or tropism and provide new hypotheses on tissue-specific mechanisms of viral infection and latency.

scholarly journals Efficacy ofBidens pilosaExtract against Herpes Simplex Virus InfectionIn VitroandIn Vivo

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Shinji Nakama ◽  
Kazumi Tamaki ◽  
Chie Ishikawa ◽  
Masayuki Tadano ◽  
Naoki Mori
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Skin Lesions ◽  
Host Cells ◽  
Raw 264.7 Cells ◽  
Bidens Pilosa ◽  
Culture Cells ◽  
Medical Plant ◽  
Simplex Virus ◽  
Hsv 1

The development of strains of herpes simplex virus (HSV) resistant to drugs has been reported among the immunocompromised patients. Thus, there is a need to develop new therapeutic agents for HSV infections. We evaluated the anti-HSV activity ofBidens pilosa(B. pilosa), a tropical weed, in tissue culture cells and a mouse model.B. pilosaextract showed potent virucidal activity. It inhibited plaque formation and suppressed virus yield in Vero and RAW 264.7 cells infected with HSV-1 and HSV-2. Both the binding of virus to host cells and penetration of virus into cells were also blocked byB. pilosa. Furthermore,B. pilosawas effective against thymidine kinase-deficient and phosphonoacetate-resistant HSV-1 strains.B. pilosatreatment increased the survival rate of HSV-infected mice and limited the development of skin lesions. Our results indicate thatB. pilosahas anti-HSV activity and is thus a potentially useful medical plant for treatment of HSV infection.

scholarly journals An epidemiologic study of herpes simplex virus type 1 and 2 infection in Japan based on type-specific serological assays

1998 ◽  
Vol 120 (2) ◽  
pp. 179-186 ◽  
Author(s):  
M. HASHIDO ◽  
F. K. LEE ◽  
A. J. NAHMIAS ◽  
H. TSUGAMI ◽  
S. ISOMURA ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Pregnant Women ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Epidemiologic Study ◽  
Clinical Manifestations ◽  
Simplex Virus ◽  
Hsv 1

A seroepidemiologic study of herpes simplex virus type 1 (HSV-1) and 2 (HSV-2) was performed on Japanese adults. Serum samples collected between 1985–9 from a total of 536 healthy adults, female prostitutes, males with sexually transmitted diseases (STD), homosexual men, and pregnant women were studied by immunodot assays using HSV type-specific antigens, glycoproteins G (gG1 and gG2). HSV-1 infections correlated mostly with age and was widely prevalent among subjects <40 years. HSV-2 prevalence varied greatly among subgroups defined by sexual activity and was associated with risk behaviours for prostitution, infection with STD, and homosexual activity. HSV-2 seroprevalence was highest among prostitutes (80%), lowest among pregnant women (7 %), and intermediate in STD patients (23%) and homosexuals (24%). Because HSV-1 infection during childhood has been decreasing, primary genital HSV-2 infection, with its higher frequency of clinical manifestations, will become a greater burden to the public health in Japan.

scholarly journals Time-Resolved Fluorometry PCR Assay for Rapid Detection of Herpes Simplex Virus in Cerebrospinal Fluid

2000 ◽  
Vol 38 (9) ◽  
pp. 3214-3218 ◽  
Author(s):  
Veijo Hukkanen ◽  
Tiina Rehn ◽  
Ritva Kajander ◽  
Minna Sjöroos ◽  
Matti Waris
Keyword(s):  
Cerebrospinal Fluid ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Pcr Assay ◽  
Time Resolved ◽  
Short Oligonucleotide ◽  
Pcr Products ◽  
The Mean ◽  
Simplex Virus ◽  
Hsv 1

We have introduced a time-resolved fluorometry (TRF)-based microwell hybridization assay for PCR products in detection of herpes simplex virus (HSV) in cerebrospinal fluid (CSF) specimens. TRF is a sensitive nonradioactive detection technique which involves the use of lanthanide chelates as fluorescent labels. We used PCR primers from the glycoprotein D genes of HSV type 1 (HSV-1) and HSV-2. The biotinylated PCR products were collected on streptavidin-coated microtitration wells and hybridized with short oligonucleotide probes, europium labeled for HSV-1 and samarium labeled for HSV-2. The TRF results were obtained as counts per second and as signal-to-noise (S/N) ratios. The sensitivity of the assay was 0.1 infectious units (PFU) of HSV in CSF specimens, and the S/N values increased with the virus amount, up to 68.5 for 103 PFU of HSV-1 and to 58.5 for 103 PFU of HSV-2, allowing semiquantitation of HSV in CSF. The primers and probes recognized all the studied 48 HSV wild-type samples, with S/N ratios of 12.4 to 190 (HSV-1) and 5.1 to 248 (HSV-2). We tested CSF specimens, 100 for each HSV type, which were HSV PCR negative by Southern blot and 22 CSF specimens which were HSV-1 or -2 PCR blot positive. In the TRF test, the mean S/N ratio for the HSV-1-negative CSF was 1.37 (standard deviation [SD] = 0.513) and for the HSV-2-negative CSF it was 1.03 (SD = 0.098). The HSV-1 blot-positive CSF yielded S/N ratios of 3.6 to 85.9, and the HSV-2 blot-positive CSF yielded ratios from 1.9 to 13. Using the mean S/N ratio for negative CSF specimens + 3 SD as the cutoff yielded all the previously HSV-positive specimens as TRF positive. The TRF PCR assay for HSV in CSF specimens is a rapid and sensitive method, improves interpretation of PCR results, and is well suited for automation.

scholarly journals Testing for Herpes Simplex Virus in Low-Volume Cerebrospinal Fluid Samples: Comparison of Three Protocols To Optimize Detection

2015 ◽  
Vol 53 (12) ◽  
pp. 3897-3899 ◽  
Author(s):  
Mark J. Espy ◽  
Cole L. Irish ◽  
Matthew J. Binnicker
Keyword(s):  
Cerebrospinal Fluid ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Medical Emergency ◽  
Herpes Simplex Virus 1 ◽  
Pcr Method ◽  
Low Volume ◽  
Simplex Virus ◽  
Testing Protocols ◽  
Hsv 1

Detection of herpes simplex virus 1 and 2 (HSV-1 and HSV-2) in cerebrospinal fluid (CSF) is a medical emergency and requires rapid, sensitive testing. However, the volume of CSF received for microbiological studies may be limited, especially from young children. In this study, we compared three testing protocols to our routine real-time PCR method to determine the most sensitive approach for detecting HSV-1 and HSV-2 in low-volume (≤100 μl) CSF.

scholarly journals Criteria for Reducing Unnecessary Testing for Herpes Simplex Virus, Varicella-Zoster Virus, Cytomegalovirus, and Enterovirus in Cerebrospinal Fluid Samples from Adults

2015 ◽  
Vol 53 (3) ◽  
pp. 887-895 ◽  
Author(s):  
Craig B. Wilen ◽  
Cynthia L. Monaco ◽  
Joan Hoppe-Bauer ◽  
Ronald Jackups ◽  
Robert C. Bucelli ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Varicella Zoster Virus ◽  
Acceptance Criteria ◽  
Validation Data ◽  
Varicella Zoster ◽  
Simplex Virus ◽  
Unnecessary Testing ◽  
Hsv 1

Excessive utilization of laboratory diagnostic testing leads to increased health care costs. We evaluated criteria to reduce unnecessary nucleic acid amplification testing (NAAT) for viral pathogens in cerebrospinal fluid (CSF) samples from adults. This is a single-center split retrospective observational study with a screening cohort from 2008 to 2012 and a validation cohort from 2013. Adults with available results for herpes simplex virus 1/2 (HSV-1/2), varicella-zoster virus (VZV), cytomegalovirus (CMV), or enterovirus (EV) NAAT with CSF samples between 2008 and 2013 were included (n= 10,917). During this study, 1.3% (n= 140) of viral NAAT studies yielded positive results. The acceptance criteria of >10 nucleated cells/μl in the CSF of immunocompetent subjects would have reduced HSV-1/2, VZV, CMV, and EV testing by 63%, 50%, 44%, and 51%, respectively, from 2008 to 2012. When these criteria were applied to the 2013 validation data set, 54% of HSV-1/2, 57% of VZV, 35% of CMV, and 56% of EV tests would have been cancelled. No clinically significant positive tests would have been cancelled in 2013 with this approach. The introduction of a computerized order entry set was associated with increased test requests, suggesting that computerized order sets may contribute to unnecessary testing. Acceptance criteria of >10 nucleated cells/μl in the CSF of immunocompetent adults for viral CSF NAAT assays would increase clinical specificity and preserve sensitivity, resulting in significant cost savings. Implementation of these acceptance criteria led to a 46% reduction in testing during a limited follow-up period.

scholarly journals Simultaneous Detection of Herpes Simplex Virus 1 and 2 in the Cerebrospinal Fluid of a Patient with Seizures and Encephalitis

2014 ◽  
Vol 53 (1) ◽  
pp. 343-345 ◽  
Author(s):  
Neil W. Anderson ◽  
William Sistrunk ◽  
Matthew J. Binnicker
Keyword(s):  
Cerebrospinal Fluid ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Simultaneous Detection ◽  
Molecular Testing ◽  
Herpes Simplex Virus 1 ◽  
First Report ◽  
Simplex Virus ◽  
Hsv 1

We report a case of a 62-year-old female with seizures and encephalitis. Molecular testing of the patient's cerebrospinal fluid was positive for both herpes simplex virus 1 and 2 (HSV-1 and HSV-2). To our knowledge, this is the first report of simultaneous detection of HSV-1 and HSV-2 in cerebrospinal fluid.

scholarly journals Intravenous Infusion of Cereport Increases Uptake and Efficacy of Acyclovir in Herpes Simplex Virus-Infected Rat Brains

2001 ◽  
Vol 45 (8) ◽  
pp. 2316-2323 ◽  
Author(s):  
Deborah J. Bidanset ◽  
Laurent Placidi ◽  
Rachel Rybak ◽  
Joyce Palmer ◽  
Jean-Pierre Sommadossi ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Rat Brain ◽  
Herpes Encephalitis ◽  
Mortality And Morbidity ◽  
Series Of Experiments ◽  
Long Term Prognosis ◽  
Simplex Virus ◽  
The Brain ◽  
Hsv 1

ABSTRACT The outcome of herpes simplex virus (HSV) infections manifesting as encephalitis in healthy or immunocompromised individuals is generally very poor with mortality rates of about 8 to 28% with treatment. The long-term prognosis of survivors is often problematic, posing the need for alternative treatments that may decrease the mortality and morbidity associated with herpes encephalitis. This study addresses one such approach that includes a temporary permeabilization of the blood-brain barrier during treatment with acyclovir (ACV). In these studies we utilized a synthetic bradykinin analog, Cereport (RMP-7), in conjunction with ACV to treat HSV infection of the brain in a rat model. Cereport, infused intravenously via the jugular vein, was shown to increase [14C]ACV uptake in both the HSV-1-infected and -uninfected rat brain by approximately two- to threefold, correlating with enhanced efficacy of ACV in various brain compartments. In another series of experiments to determine efficacy, various doses of unlabeled ACV were administered during infusion with RMP-7. The decrease in viral titers in the temporal regions of the brain after 5 days of treatment suggested that this approach enhanced the efficacy of ACV treatment. These data indicated that Cereport infused with ACV enhances both the penetration and efficacy of this drug in the treatment of an experimental HSV-1 infection of the rat brain.

scholarly journals Importance of NKT Cells in Resistance to Herpes Simplex Virus, Fate of Virus-Infected Neurons, and Level of Latency in Mice

2008 ◽  
Vol 82 (22) ◽  
pp. 11073-11083 ◽  
Author(s):  
Branka Grubor-Bauk ◽  
Jane Louise Arthur ◽  
Graham Mayrhofer
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Neuronal Damage ◽  
Nkt Cells ◽  
Skin Lesions ◽  
The Central Nervous System ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Herpes simplex virus type 1 (HSV-1) produces acute mucocutaneous infections, spread to sensory ganglia, and establishment of latency. In addition, neurovirulent strains have potential to invade the central nervous system (CNS), with potentially a lethal outcome. Early activation of defenses at all stages is essential to limit virus load and reduce the risk of neuronal damage, extensive zosteriform skin lesions, and catastrophic spread to the CNS. NKT cells respond rapidly, and we have shown previously that CD1d-deficient mice are compromised in controlling a neuroinvasive isolate of HSV-1. We now compare infection in Jα18 GKO and CD1d GKO mice, allowing direct assessment of the importance of invariant Vα14+ NKT cells and deduction of the role of the CD1d-restricted NKT cells with diverse T-cell receptors. The results indicate that both subsets of NKT cells contribute to virus control both in the afferent phase of infection and in determining the mortality, neuroinvasion, loss of sensory neurons, size of zosteriform, lesions and levels of latency. In particular, both are crucial determinants of clinical outcome, providing protection equivalent to a 1-log dose of virus. These NKT cells can be expected to provide protection at doses of virus that might be encountered naturally.

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