Neonatal herpes encephalitis caused by a virologically confirmed acyclovir-resistant herpes simplex virus 1 strain.
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ABSTRACT:
SUBMITTER: Kakiuchi S
PROVIDER: S-EPMC3536242 | biostudies-literature | 2013 Jan
REPOSITORIES: biostudies-literature
Publications
Neonatal herpes encephalitis caused by a virologically confirmed acyclovir-resistant herpes simplex virus 1 strain.
Kakiuchi Satsuki S Nonoyama Shigeaki S Wakamatsu Hajime H Kogawa Kazuhiro K Wang Lixin L Kinoshita-Yamaguchi Hitomi H Takayama-Ito Mutsuyo M Lim Chang-Kweng CK Inoue Naoki N Mizuguchi Masashi M Igarashi Takashi T Saijo Masayuki M
Journal of clinical microbiology 20121024 1
A neonate with herpes simplex virus 1 encephalitis was treated with intravenous acyclovir. During the course of therapy, the infection became intractable to the treatment and a mutation in the viral thymidine kinase gene (nucleotide G375T, amino acid Q125H) developed. This mutation was demonstrated in vitro to confer acyclovir resistance. ...[more]
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Project description:We report an immunocompetent woman with multisystem organ failure following herpes simplex virus type 2 (HSV-2) hepatitis. After she initially responded to intravenous acyclovir, she was switched to oral valacyclovir. She developed respiratory failure and opportunistic infections and died. Autopsy confirmed disseminated HSV infection, and lung tissue grew acyclovir-resistant HSV-2.
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Project description:BackgroundPoor neurodevelopmental outcomes and recurrences of cutaneous lesions remain unacceptably frequent among survivors of neonatal herpes simplex virus (HSV) disease.MethodsWe enrolled neonates with HSV disease in two parallel, identical, double-blind, placebo-controlled studies. Neonates with central nervous system (CNS) involvement were enrolled in one study, and neonates with skin, eye, and mouth involvement only were enrolled in the other. After completing a regimen of 14 to 21 days of parenteral acyclovir, the infants were randomly assigned to immediate acyclovir suppression (300 mg per square meter of body-surface area per dose orally, three times daily for 6 months) or placebo. Cutaneous recurrences were treated with open-label episodic therapy.ResultsA total of 74 neonates were enrolled--45 with CNS involvement and 29 with skin, eye, and mouth disease. The Mental Development Index of the Bayley Scales of Infant Development (in which scores range from 50 to 150, with a mean of 100 and with higher scores indicating better neurodevelopmental outcomes) was assessed in 28 of the 45 infants with CNS involvement (62%) at 12 months of age. After adjustment for covariates, infants with CNS involvement who had been randomly assigned to acyclovir suppression had significantly higher mean Bayley mental-development scores at 12 months than did infants randomly assigned to placebo (88.24 vs. 68.12, P=0.046). Overall, there was a trend toward more neutropenia in the acyclovir group than in the placebo group (P=0.09).ConclusionsInfants surviving neonatal HSV disease with CNS involvement had improved neurodevelopmental outcomes when they received suppressive therapy with oral acyclovir for 6 months. (Funded by the National Institute of Allergy and Infectious Diseases; CASG 103 and CASG 104 ClinicalTrials.gov numbers, NCT00031460 and NCT00031447, respectively.).
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Project description:BackgroundAcyclovir (ACV)-resistant (ACVr) herpes simplex virus type 1 (HSV-1) infections are concern in immunocompromised patients. Most clinical ACVr HSV-1 isolates have mutations in the viral thymidine kinase (vTK) genes. The vTK-associated ACVr HSV-1 shows reduced virulence, but the association between the level of resistance and the virulence of the vTK-associated ACVr HSV-1 is still unclear.MethodsThe virulence in mice of 5 vTK-associated ACVr HSV-1 clones with a variety of ACV sensitivities, when inoculated through intracerebral and corneal routes, was evaluated in comparison with ACV-sensitive (ACVs) parent HSV-1 TAS.ResultsAlthough all the 5 ACVr HSV-1 clones and ACVs HSV-1 TAS showed a similar single-step growth capacity in vitro, the virulence of ACVr HSV-1 clones significantly decreased. A 50% lethal dose (LD50) of each clone was closely correlated with 50% inhibitory concentrations (IC50), demonstrating that the higher the ACV-sensitvity, the the higher the virulence among the ACVr clones. One of the ACVr HSV-1 clones with a relatively low IC50 value maintained similar virulence to that of the parent TAS. The infection in mice with ACVr HSV-1 due to a single amino acid substitution in vTK induced local diseases, keratitis and dermatitis, while vTK-deficient clone did not.ConclusionsA statistically significant correlation between the virulence and susceptibility to ACV among ACVr HSV-1 clones was demonstrated.
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Project description:Pseudo-seq was used to measure differences in the extent of pseudouridine (Ψ) modification in rRNA from human cell lines with heterozygous, and homozygous disruptions of SNORA31.
2019-10-14 | GSE102078 | GEO