scholarly journals THE ETIOLOGIC AGENTS OF VARICELLA AND HERPES ZOSTER

1958 ◽  
Vol 108 (6) ◽  
pp. 869-890 ◽  
Author(s):  
Thomas H. Weller ◽  
Helen M. Witton
Keyword(s):  
Herpes Zoster ◽  
Kidney Tissue ◽  
Focal Lesions ◽  
Cell Sheets ◽  
Varicella Zoster ◽  
Close Relationship ◽  
Embryonic Skin ◽  
Simplex Virus ◽  
Specific Fixation

The preparation of antigenic materials capable of specific fixation of complement in the presence of convalescent phase sera from patients with varicella and herpes zoster is described. Satisfactory antigens were obtained by the repetitive harvest and subsequent concentration of the pooled nutrient fluids from bottle cultures of human embryonic skin-muscle tissue or of monkey kidney tissue infected with varicella or herpes zoster viruses. Specific fixation of complement was also demonstrated with antigens prepared from extracts of the infected cell sheets harvested from bottle cultures. In individuals with varicella, complement-fixing antibody usually appeared in the serum 4 or 5 days after the development of the exanthem and further significant increases in titer were characteristically observed during the 2nd week of illness. The complement-fixing antibody response in herpes zoster tended to follow the same pattern as in varicella, with the exception that in sera from some individuals relatively high titers were present in the acute phase specimen. Complement-fixing antigens prepared from varicella strains or from a zoster strain reacted to essentially the same degree with convalescent sera from the homologous and the heterologous clinical entities. The varicella-zoster antigens did not fix complement in the presence of paired sera obtained from a limited number of individuals with primary infections due to herpes simplex virus or from individuals with generalized vaccinia infection. Specific inhibition in vitro of the focal cytopathic process produced by the varicella-zoster viruses was demonstrated. This was accomplished by the incorporation of the sera under test as constituents of nutrient media of the cultures, either prior to or at the time of their inoculation with virus. The neutralization of focal cytopathogenicity thus obtained was relative in degree and never absolute; it was therefore assayed by repetitive counts of the number of focal lesions per culture in the various test groups. Inhibition of varicella-zoster viral cytopathogenicity occurred in the presence of convalescent serum from either clinical entity. The results of the immunologic studies with the viruses of herpes zoster and varicella as propagated in vitro are considered as providing further evidence in support of the concept of the close relationship and probable identity of the two agents.

scholarly journals Evaluation of RealStar® Alpha Herpesvirus PCR Kit for Detection of HSV-1, HSV-2, and VZV in Clinical Specimens

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Cyril C. Y. Yip ◽  
Siddharth Sridhar ◽  
Kit-Hang Leung ◽  
Andrew K. W. Cheng ◽  
Kwok-Hung Chan ◽  
...  
Keyword(s):  
Real Time ◽  
Real Time Pcr ◽  
Test Performance ◽  
Analytical Sensitivity ◽  
Pcr Assay ◽  
Clinical Specimens ◽  
Varicella Zoster ◽  
Simplex Virus ◽  
Hsv 1

Several commercial PCR kits are available for detection of herpes simplex virus (HSV) and varicella zoster virus (VZV), but the test performance of one CE-marked in vitro diagnostic kit—RealStar® alpha Herpesvirus PCR Kit—has not been well studied. This study evaluated the performance of RealStar® alpha Herpesvirus PCR Kit 1.0 on the LightCycler® 480 Instrument II for detection and differentiation of HSV-1, HSV-2, and VZV in human clinical specimens. We evaluated the analytical sensitivity of the RealStar® and in-house multiplex real-time PCR assays using serial dilutions of nucleic acids extracted from clinical specimens. The analytical sensitivity of the RealStar® assay was 10, 32, and 100 copies/reaction for HSV-1, HSV-2, and VZV, respectively, which was slightly higher than that of the in-house multiplex real-time PCR assay. Reproducibility of the cycle threshold (Cp) values for each viral target was satisfactory with the intra- and interassay coefficient of variation values below 5% for both assays. One-hundred and fifty-three clinical specimens and 15 proficiency testing samples were used to evaluate the diagnostic performance of RealStar® alpha Herpesvirus PCR Kit against the in-house multiplex real-time PCR assay. The RealStar® assay showed 100% sensitivity and specificity when compared to the in-house assay. Cp values of the RealStar® and in-house assays showed excellent correlation. RealStar® alpha Herpesvirus PCR is a sensitive, specific, and reliable assay for the detection of HSV-1, HSV-2, and VZV, with less extensive verification requirements compared to a laboratory developed assay.

scholarly journals Amphipathic DNA Polymers Exhibit Antiherpetic Activity In Vitro and In Vivo

2008 ◽  
Vol 52 (8) ◽  
pp. 2727-2733 ◽  
Author(s):  
David I. Bernstein ◽  
Nathalie Goyette ◽  
Rhonda Cardin ◽  
Earl R. Kern ◽  
Guy Boivin ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Broad Spectrum ◽  
Parent Compound ◽  
Human Herpesvirus ◽  
Varicella Zoster ◽  
Barr Virus ◽  
Simplex Virus ◽  
Acid Stable

ABSTRACT Phosphorothioated oligonucleotides have a sequence-independent antiviral activity as amphipathic polymers (APs). The activity of these agents against herpesvirus infections in vitro and in vivo was investigated. The previously established sequence-independent, phosphorothioation-dependent antiviral activity of APs was confirmed in vitro by showing that a variety of equivalently sized homo- and heteropolymeric AP sequences were similarly active against herpes simplex virus type 1 (HSV-1) infection in vitro compared to the 40mer degenerate parent compound (REP 9), while the absence of phosphorothioation resulted in the loss of antiviral activity. In addition, REP 9 demonstrated in vitro activity against a broad spectrum of other herpesviruses: HSV-2 (50% effective concentration [EC50], 0.02 to 0.06 μM), human cytomegalovirus (EC50, 0.02 to 0.13 μM), varicella zoster virus (EC50, <0.02 μM), Epstein-Barr virus (EC50, 14.7 μM) and human herpesvirus types 6A/B (EC50, 2.9 to 10.2 μM). The murine microbicide model of genital HSV-2 was then used to evaluate in vivo activity. REP 9 (275 mg/ml) protected 75% of animals from disease and infection when provided 5 or 30 min prior to vaginal challenge. When an acid-stable analog (REP 9C) was used, 75% of mice were protected when treated with 240 mg/ml 5 min prior to infection (P < 0.001), while a lower dose (100 mg/ml) protected 100% of the mice (P < 0.001). The acid stable REP 9C formulation also provided protection at 30 min (83%, P < 0.001) and 60 min (50%, P = 0.07) against disease. These observations suggest that APs may have microbicidal activity and potential as broad-spectrum antiherpetic agents and represent a novel class of agents that should be studied further.

scholarly journals Silicone-Acyclovir Controlled Release Devices Suppress Primary Herpes Simplex Virus-2 and Varicella Zoster Virus InfectionsIn Vitro

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Carol L. Berkower ◽  
Nicole M. Johnson ◽  
Stephen B. Longdo ◽  
Shenika O. McGusty-Robinson ◽  
Samantha L. Semenkow ◽  
...  
Keyword(s):  
Slow Release ◽  
Clinical Symptoms ◽  
Drug Regimen ◽  
Daily Basis ◽  
Varicella Zoster ◽  
Simplex Virus ◽  
Hsv 1

Following initial infection, herpesviruses retreat into a permanent latent state with periodic reactivation resulting in an enhanced likelihood of transmission and clinical disease. The nucleoside analogue acyclovir reduces clinical symptoms of the three human alpha herpesviruses, HSV-1, HSV-2, and VZV. Long-term administration of acyclovir (ACV) can reduce the frequency and severity of reactivation, but its low bioavailability and short half-life require a daily drug regimen. Our lab is working to develop a subcutaneous delivery system to provide long-lasting, sustained release of ACV. Previously, we demonstrated that an implantable silicone (MED-4050) device, impregnated with ACV protected against HSV-1 bothin vitroandin vivo. Here, we extend ourin vitroobservations to include protection against both HSV-2 and VZV. We also demonstrate protection against HSV-2in vitrousing MED-4750, a silicone polymer designed for long-term use in humans. When release of ACV from MED-4750 is quantitated on a daily basis, an initial burst of 5 days is observed, followed by a long period of slow release with near-zero-order kinetics, with an average daily release of 1.3923 ± 0.5908 μg ACV over days 20–60. Development of a slow-release implant has the potential to significantly impact the treatment of human alpha herpesvirus infections.

scholarly journals What is the True Etiology of “Recurrent Shingles”?

2021 ◽  
Vol 5 (1) ◽  
pp. 7-12
Author(s):  
Ramya Vangipuram ◽  
Harrison Nguyen ◽  
Stephen Tyring
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Zoster ◽  
Herpes Simplex ◽  
Varicella Zoster Virus ◽  
Varicella Zoster ◽  
Dermatology Clinic ◽  
Simplex Infection ◽  
Common Diagnosis ◽  
Recurrent Herpes ◽  
Simplex Virus

Purpose:  To determine the true etiology of cases of putative recurrent shingles referred to a dermatology clinic. Methods: A prospective cohort study of patients aged 15-87 years with reported recurrent herpes zoster was conducted. Vesicular fluid and serology for herpes simplex 1, 2, and varicella zoster virus immunoglobulins were obtained from patients presenting with vesicles. Biopsies were obtained from patients with ambiguous presentations. Results:  44 patients (56%) had evidence of herpes simplex virus infection. 32% of patients had positive herpes simplex virus cultures or polymerase chain reaction sequencing, and 24% additional patients were diagnosed with presumptive simplex infection based on elevated antibody titers. 44% of patients had a diagnosis other than zoster or simplex. One individual had a positive viral culture for varicella zoster virus. 99% of patients who presented with suspected recurrent herpes zoster had no definitive evidence of varicella zoster virus reactivation. Conclusions:  The most common diagnosis was herpes simplex infection. Our results suggest that true recurrent shingles in immunocompetent patients is rare.

A Comparative Study of the in vitro and in vivo Antiviral Activities of Acyclovir and Penciclovir

1995 ◽  
Vol 6 (2) ◽  
pp. 89-97 ◽  
Author(s):  
P. Ertl ◽  
W. Snowden ◽  
D. Lowe ◽  
W. Miller ◽  
P. Collins ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Varicella Zoster ◽  
Significant Difference ◽  
Simplex Virus ◽  
Hsv 1

The antiviral properties of the compounds acyclovir (ACV) and penciclovir (PCV) have been compared in a number of in vitro and in vivo assays. In vitro, both compounds had good activity against herpes simplex virus type 1 (HSV-1) and varicella-zoster virus (VZV), although ACV showed statistically significant superiority. In addition, ACV had greater activity against herpes simplex virus type 2 (HSV-2), human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV). We examined the effect of time of addition and removal of ACV and PCV under a variety of conditions and found similar results with the two compounds under most conditions. However, at a high multiplicity of infection, when all of the cells would be expected to be synchronously expressing large amounts of the viral thymidine kinase, short exposures to PCV appeared to be superior to similar exposures to ACV. In the HSV-1 zosteriform mouse model there was no significant difference between the activities of ACV and PCV, or its prodrug famciclovir (FCV), in once- or twice-daily treatment. The possible significance of these results and those previously reported on the activity of the compounds in humans is discussed.

scholarly journals Inhibition of Herpesvirus Replication by 5-Substituted 4′-Thiopyrimidine Nucleosides

2009 ◽  
Vol 53 (12) ◽  
pp. 5251-5258 ◽  
Author(s):  
Mark N. Prichard ◽  
Debra C. Quenelle ◽  
Caroll B. Hartline ◽  
Emma A. Harden ◽  
Geraldine Jefferson ◽  
...  
Keyword(s):  
Human Herpesvirus ◽  
Good Activity ◽  
Varicella Zoster ◽  
Barr Virus ◽  
Resistant Strains ◽  
Epstein Barr ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT A series of 4′-thionucleosides were synthesized and evaluated for activities against orthopoxviruses and herpesviruses. We reported previously that one analog, 5-iodo-4′-thio-2′-deoxyuridine (4′-thioIDU), exhibits good activity both in vitro and in vivo against two orthopoxviruses. This compound also has good activity in cell culture against many of the herpesviruses. It inhibited the replication of herpes simplex virus type 1 (HSV-1), HSV-2, and varicella-zoster virus with 50% effective concentrations (EC50s) of 0.1, 0.5, and 2 μM, respectively. It also inhibited the replication of human cytomegalovirus (HCMV) with an EC50 of 5.9 μM but did not selectively inhibit Epstein-Barr virus, human herpesvirus 6, or human herpesvirus 8. While acyclovir-resistant strains of HSV-1 and HSV-2 were comparatively resistant to 4′-thioIDU, it retained modest activity (EC50s of 4 to 12 μM) against these strains. Some ganciclovir-resistant strains of HCMV also exhibited reduced susceptibilities to the compound, which appeared to be related to the specific mutations in the DNA polymerase, consistent with the observed incorporation of the compound into viral DNA. The activity of 4′-thioIDU was also evaluated using mice infected intranasally with the MS strain of HSV-2. Although there was no decrease in final mortality rates, the mean length of survival after inoculation increased significantly (P < 0.05) for all animals receiving 4′-thioIDU. The findings from the studies presented here suggest that 4′-thioIDU is a good inhibitor of some herpesviruses, as well as orthopoxviruses, and this class of compounds warrants further study as a therapy for infections with these viruses.

scholarly journals In Vitro Activity and Mechanism of Action of Methylenecyclopropane Analogs of Nucleosides against Herpesvirus Replication

2005 ◽  
Vol 49 (3) ◽  
pp. 1039-1045 ◽  
Author(s):  
Earl R. Kern ◽  
Nicole L. Kushner ◽  
Caroll B. Hartline ◽  
Stephanie L. Williams-Aziz ◽  
Emma A. Harden ◽  
...  
Keyword(s):  
Mechanism Of Action ◽  
Human Herpesvirus ◽  
Murine Cytomegalovirus ◽  
Enzyme Linked Immunosorbent Assay ◽  
Herpesvirus Type ◽  
Varicella Zoster ◽  
Barr Virus ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT We have reported previously that methylenecyclopropane analogs of nucleosides have excellent activity against certain members of the herpesvirus family. A second generation, the 2,2-bis-hydroxymethyl derivatives, were synthesized, and 18 compounds were tested for activity in vitro against herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), human and murine cytomegalovirus (HCMV and MCMV), varicella-zoster virus (VZV), and Epstein-Barr virus (EBV). Selected analogs were also evaluated against human herpesvirus type 6 (HHV-6) and HHV-8. None of the 18 compounds had activity against HSV-1 or HSV-2, but four were active against VZV by plaque reduction (PR) assay at 50% effective concentration (EC50) levels of ≤50 μM. Six of the 18 compounds were active against HCMV by cytopathic effect or PR assays with EC50s of 0.5 to 44 μM, and all were active against MCMV by PR (0.3 to 54 μM). Four of the compounds were active against EBV by enzyme-linked immunosorbent assay (<0.3 to 4.4 μM). Four compounds with CMV activity were also active against HHV-6A and HHV-6B (0.7 to 28 μM), and three compounds were active against HHV-8 (5.5 to 16 μM). One of these, ZSM-I-62, had particularly good activity against CMV, HHV-6, and HHV-8, with EC50s of 0.7 to 8 μM. Toxicity was evaluated in adherent and nonadherent cells, and minimal cytotoxicity was observed. Mechanism of action studies with HCMV suggested that these compounds are phosphorylated by the ppUL97 phosphotransferase and are potent inhibitors of viral DNA synthesis. These results indicate that at least one of these compounds may have potential for use in treating CMV and other herpesvirus infections in humans.

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