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1.
Pharmacol Res Perspect ; 12(6): e70028, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39428714

RESUMO

Antiviral use has been linked to encephalopathy and elevated serum creatinine concentrations in individuals with chronic kidney disease (CKD) in case reports. Using linked healthcare data in Ontario, we conducted a population-based cohort study on adults aged ≥66 years not receiving dialysis and newly prescribed oral acyclovir, valacyclovir, or famciclovir in the outpatient setting (2008-2022) at higher versus lower doses. The primary composite outcome, a hospital visit with encephalopathy or acute kidney injury (AKI) within 14 days of initiating antiviral treatment, was examined in a primary cohort. AKI was assessed in a secondary cohort of older adults with CKD with available linked hospital-based laboratory (lab) data. We used inverse probability of treatment weighting on the propensity score to balance comparison groups on baseline health. Weighted risk ratios (RR) and risk differences (RD) were obtained using modified Poisson and binomial regression. In the primary cohort, higher- versus lower-dose antiviral was not associated with an increased 14-day risk of hospital visit with encephalopathy or AKI. However, Higher- versus lower-dose antiviral was associated with a higher risk of a hospital visit with AKI when assessed using lab values (weighted number of events, 70 of 8407 [0.83%] versus 18 of 8230 [0.22%], respectively; weighted RR, 3.83 [95% CI, 1.87-7.87]; weighted RD, 0.62% [95% CI, 0.37%-0.86%]). In older adults with CKD, starting an antiviral at a higher versus lower dose was associated with a higher risk of AKI, although the absolute risk of this event was <1%.


Assuntos
Injúria Renal Aguda , Antivirais , Insuficiência Renal Crônica , Humanos , Idoso , Masculino , Antivirais/efeitos adversos , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Feminino , Insuficiência Renal Crônica/complicações , Idoso de 80 Anos ou mais , Injúria Renal Aguda/induzido quimicamente , Estudos de Coortes , Aciclovir/efeitos adversos , Aciclovir/administração & dosagem , Aciclovir/uso terapêutico , Ontário/epidemiologia , Valaciclovir/uso terapêutico , Valaciclovir/administração & dosagem , Valaciclovir/efeitos adversos , Famciclovir , Relação Dose-Resposta a Droga , Infecções por Herpesviridae/complicações , Infecções por Herpesviridae/tratamento farmacológico
3.
BMJ Case Rep ; 17(9)2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39256172

RESUMO

Herpes zoster (HZ), commonly known as shingles, is a painful blistering rash in dermatomal distribution, caused by the reactivation of varicella-zoster virus (VZV) that was acquired during a primary varicella infection. While commonly afflicting adults, cases of HZ in paediatric patients are infrequently reported. Such cases are predominantly reported in children who have had prior exposure to VZV, either during pregnancy, early childhood or have been vaccinated with live attenuated VZV. This report presents the first known case to our knowledge of HZ as the initial manifestation of a VZV infection in an immunocompetent toddler in the UK. The report details the chronology of the infection event and discusses the clinical context behind HZ presentations in paediatrics globally. It provides a compelling illustration of the uncommon presentation of VZV infection in an immunocompetent child devoid of antecedent virus exposure, thus meriting acknowledgement and potentially further investigation as to the cause.


Assuntos
Herpes Zoster , Herpesvirus Humano 3 , Humanos , Herpes Zoster/diagnóstico , Herpes Zoster/tratamento farmacológico , Herpesvirus Humano 3/isolamento & purificação , Antivirais/uso terapêutico , Aciclovir/uso terapêutico , Lactente , Masculino , Infecção pelo Vírus da Varicela-Zoster/diagnóstico , Infecção pelo Vírus da Varicela-Zoster/complicações , Infecção pelo Vírus da Varicela-Zoster/tratamento farmacológico , Feminino , Pré-Escolar
4.
PLoS One ; 19(9): e0309733, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39231124

RESUMO

Combining different drugs synergistically is an essential aspect of developing effective treatments. Although there is a plethora of research on computational prediction for new combination therapies, there is limited to no research on combination therapies in the treatment of viral diseases. This paper proposes AI-based models for predicting novel antiviral combinations to treat virus diseases synergistically. To do this, we assembled a comprehensive dataset comprising information on viral strains, drug compounds, and their known interactions. As far as we know, this is the first dataset and learning model on combination therapy for viruses. Our proposal includes using a random forest model, an SVM model, and a deep model to train viral combination therapy. The machine learning models showed the highest performance, and the predicted values were validated by a t-test, indicating the effectiveness of the proposed methods. One of the predicted combinations of acyclovir and ribavirin has been experimentally confirmed to have a synergistic antiviral effect against herpes simplex type-1 virus, as described in the literature.


Assuntos
Antivirais , Sinergismo Farmacológico , Quimioterapia Combinada , Aprendizado de Máquina , Antivirais/uso terapêutico , Antivirais/farmacologia , Humanos , Ribavirina/uso terapêutico , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 1/fisiologia , Aciclovir/uso terapêutico , Aciclovir/administração & dosagem , Aciclovir/farmacologia , Viroses/tratamento farmacológico
5.
Tidsskr Nor Laegeforen ; 144(11)2024 Sep 24.
Artigo em Inglês, Norueguês | MEDLINE | ID: mdl-39319764

RESUMO

Background: Acute functional decline is a common reason for hospital admission for older people, often caused by an acute deterioration of an underlying chronic illness. However, occasionally a rare condition is detected. Case presentation: A woman in her eighties was admitted to hospital with acute functional decline. Hyponatraemia, urinary tract infection and pulmonary embolism were initially diagnosed. She developed increasing difficulties in using her legs, and assessment led to the diagnosis of varicella- zoster virus myelitis, which was treated with intravenous acyclovir. After a brief stay in the rehabilitation unit, the patient's condition acutely deteriorated, leading to readmission with neurovascular septic embolism and microvascular haemorrhage in the brain. Anticoagulation was terminated. After 52 days she was discharged to a nursing home for further rehabilitation. Interpretation: Our article presents a case of acute functional decline caused by a rare condition. Collaboration between the geriatric, neurological and infectious disease departments was needed. When treated rapidly with targeted therapy, the prognosis for myelitis is often good.


Assuntos
Aciclovir , Antivirais , Mielite , Infecção pelo Vírus da Varicela-Zoster , Humanos , Feminino , Mielite/virologia , Mielite/diagnóstico , Mielite/tratamento farmacológico , Antivirais/uso terapêutico , Infecção pelo Vírus da Varicela-Zoster/diagnóstico , Infecção pelo Vírus da Varicela-Zoster/tratamento farmacológico , Infecção pelo Vírus da Varicela-Zoster/complicações , Idoso de 80 Anos ou mais , Aciclovir/uso terapêutico , Aciclovir/administração & dosagem , Herpesvirus Humano 3/isolamento & purificação , Imageamento por Ressonância Magnética , Doença Aguda
6.
Rev Med Virol ; 34(5): e2574, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39090526

RESUMO

Herpes simplex virus (HSV) infections in allogeneic haematopoietic stem cell transplantation (HSCT) recipients pose significant challenges, with higher incidence, severity, and risk of emergence of resistance to antivirals due to impaired T-cell mediated immunity. This literature review focuses on acyclovir-refractory/resistant HSV infections in HSCT recipients. The review addresses the efficacy of antiviral prophylaxis, the incidence of acyclovir-refractory/resistant HSV infections, and the identification of risk factors and potential prognostic impact associated with those infections. Additionally, alternative therapeutic options are discussed. While acyclovir prophylaxis demonstrates a significant benefit in reducing HSV infections in HSCT recipients and, in some cases, overall mortality, concerns arise about the emergence of drug-resistant HSV strains. Our systematic review reports a median incidence of acyclovir-resistant HSV infections of 16.1%, with an increasing trend in recent years. Despite limitations in available studies, potential risk factors of emergence of HSV resistance to acyclovir include human leucocyte antigen (HLA) mismatches, myeloid neoplasms and acute leukaemias, and graft-versus-host disease (GVHD). Limited evidences suggest a potentially poorer prognosis for allogeneic HSCT recipients with acyclovir-refractory/resistant HSV infection. Alternative therapeutic approaches, such as foscarnet, cidofovir, topical cidofovir, optimised acyclovir dosing, and helicase-primase inhibitors offer promising options but require further investigations. Overall, larger studies are needed to refine preventive and therapeutic strategies for acyclovir-refractory/resistant HSV infections in allogeneic HSCT recipients and to identify those at higher risk.


Assuntos
Aciclovir , Antivirais , Farmacorresistência Viral , Transplante de Células-Tronco Hematopoéticas , Herpes Simples , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Herpes Simples/tratamento farmacológico , Herpes Simples/virologia , Herpes Simples/terapia , Antivirais/uso terapêutico , Aciclovir/uso terapêutico , Simplexvirus/efeitos dos fármacos , Simplexvirus/fisiologia , Fatores de Risco , Transplantados , Incidência
8.
Photodiagnosis Photodyn Ther ; 49: 104282, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39009206

RESUMO

OBJECTIVE: This study aimed to determine the effect of Photobiomodulation therapy (PBMT) in the treatment of recurrent herpes labialis (RHL), one of the most common herpes simplex virus type 1 infections. MATERIAL AND METHODS: In this randomized double blind controlled trial, Twenty-two symptomatic patients with RHL were enrolled. The patients were randomly allocated into one group (5 % acyclovir cream with 940±10 nm wavelength and 4 J/cm2 energy density and 100 mW output power) and another group (5 % Acyclovir 5 times/5 days and sham laser). Lesion size, and pain intensity were considered as the outcome at baseline, 1st 2nd and 3rd days postoperatively. RESULTS: Pain intensity in PBM + Acyclovir group was significantly lower than Acyclovir without PBM group in both two and three days after intervention (p < 0.001). The lesion size in case group was significantly lower on 7 and 10 days (p < 0.05). Patients in the treatment group were significantly more satisfied with their treatment process (p = 0.008). CONCLUSION: PBMT can be used as an adjuvant tool to acyclovir cream, due to higher potential in reducing postoperative pain, lesion size and also patients satisfaction.


Assuntos
Aciclovir , Antivirais , Herpes Labial , Terapia com Luz de Baixa Intensidade , Humanos , Herpes Labial/tratamento farmacológico , Herpes Labial/radioterapia , Feminino , Terapia com Luz de Baixa Intensidade/métodos , Aciclovir/uso terapêutico , Adulto , Masculino , Método Duplo-Cego , Antivirais/uso terapêutico , Pessoa de Meia-Idade , Recidiva , Terapia Combinada
9.
Afr Health Sci ; 24(1): 91-93, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38962355

RESUMO

This case report describes a pregnant patient with recent diagnosis of Human Immuno-Deficiency Virus (HIV) infection initiated on Anti-Retroviral Therapy (ART) in the second trimester, as well as high dose acyclovir high for large infected genital warts. She had no other HIV related opportunistic infections, and no prior anti tuberculosis treatment or preventive medication. Despite little response to acyclovir, patient was continuing on acyclovir for over 4 months. She subsequently developed recurrent anemia requiring frequent transfusion (14 units in total) over a 6-week period. On stopping acyclovir, the anemia subsided, a few weeks later she had a normal delivery, followed by surgical removal of the warts. At a follow-up 8 months later, she was well, with a healthy baby, and reported no other episodes of blood transfusion.


Assuntos
Aciclovir , Anemia , Antivirais , Infecções por HIV , Complicações Infecciosas na Gravidez , Recidiva , Humanos , Feminino , Gravidez , Aciclovir/uso terapêutico , Aciclovir/efeitos adversos , Aciclovir/administração & dosagem , Infecções por HIV/tratamento farmacológico , Infecções por HIV/complicações , Complicações Infecciosas na Gravidez/tratamento farmacológico , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Adulto , Uganda , Resultado do Tratamento , Herpes Genital/tratamento farmacológico , Transfusão de Sangue
10.
Georgian Med News ; (349): 51-53, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38963201

RESUMO

The etiology of meningoencephalitis with COVID19 is coronavirus and herpetic. Secondary herpes infection is associated with immunological dysregulation or with the use of tocilizumab. Differential diagnosis of the etiology of encephalitis is important, because acyclovir is effective for herpes infection. Case Report: A 38-year-old man with right-sided lower lobe pneumonia COVID-19 was hospitalized in the infectious diseases department. On the 6th day of hospitalization, the patient developed respiratory failure and was transferred to the anesthesiology and intensive care unit. We started noninvasive lung ventilation, which was ineffective, and the patient was intubated and started on MVL. MRI data: encephalitis of the frontal, parietal and occipital lobes on the left. On the 14th day, we detected a herpetic rash on the legs and thighs in the projection of the sciatic nerve. We suspected the patient had a herpes infection and prescribed acyclovir 1000 mg intravenously 3 times a day. On the 32nd day, a blood test by IFA revealed class G antibodies to the Viral Capsid Antigen (VCA) of the Epstein-Barr virus. On the 58th day, he was discharged home in a satisfactory condition. Given the extraordinary strain on healthcare systems amid the pandemic, there are challenges in diagnosing herpes infection in patients with COVID-19. The alertness of doctors about the development of herpes infection and its clinical signs is important. This will allow for early antiherpetic treatment.


Assuntos
Aciclovir , COVID-19 , Humanos , Masculino , Adulto , COVID-19/complicações , Aciclovir/uso terapêutico , SARS-CoV-2 , Antivirais/uso terapêutico , Imageamento por Ressonância Magnética
11.
Brain Inj ; 38(12): 1046-1051, 2024 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-38963013

RESUMO

OBJECTIVE: Herpes simplex virus encephalitis (HSVE) is associated with significant morbidity and mortality. Here, we present the occurrence of HSVE in a 36-year-old immunocompetent patient following craniotomy for a traumatic acute subdural hematoma (ASDH). METHODS: Imaging after four days of progressive headache following a fall with head-strike demonstrated a 1 cm thick left holohemispheric ASDH with significant cerebral compression, edema, and 8 mm of left-to-right midline shift, and an emergent craniotomy and ASDH evacuation were performed, with additional treatment needed for reaccumulation. Postoperatively, the patient developed a worsening leukocytosis, became febrile, and was hypotensive requiring vasopressor support. RESULTS: Despite empiric antibiotics, the patient remained persistently febrile with significant leukocytosis. Repeat head CT showed a new left insular hypodensity and a subsequent viral encephalitis panel was positive for HSV-1. The patient was then started on intravenous acyclovir, with progressive neurological exam improvement. Of note, the patient was noted to have a positive serum HSV-1 IgG antibody titer, indicative of prior infection. CONCLUSIONS: Given the known systemic immunosuppression in brain injury and the high prevalence of HSV seropositivity, clinicians should consider the possibility of HSVE from HSV reactivation in TBI patients with persistent fever, leukocytosis, and/or neurological deficits without an obvious etiology.


Assuntos
Lesões Encefálicas Traumáticas , Encefalite por Herpes Simples , Humanos , Encefalite por Herpes Simples/complicações , Adulto , Masculino , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/cirurgia , Ativação Viral , Craniotomia/efeitos adversos , Herpesvirus Humano 1 , Antivirais/uso terapêutico , Aciclovir/uso terapêutico , Hematoma Subdural Agudo/etiologia , Hematoma Subdural Agudo/cirurgia , Complicações Pós-Operatórias
12.
BMJ Case Rep ; 17(7)2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38991567

RESUMO

We present a case of a primigravida in her 30s who had a caesarean delivery of dichorionic diamniotic twins at 33 weeks of gestation. Her postpartum course was complicated by a herpes simplex virus (HSV) infection of her nipple, found after her neonates were diagnosed with HSV encephalitis. She was evaluated at her 3-week postpartum visit and reported that her neonates were concurrently admitted to the neonatal intensive care unit with disseminated neonatal HSV-1. The patient and her partner were in a monogamous relationship with no known history of HSV. Physical examination demonstrated a vertical fissure on the face of her right nipple and a small cluster of vesicles on her left hand. PCR swabs of the lesions were positive for HSV-1 at both locations. The patient was started on oral valacyclovir 1000 mg two times per day, topical acyclovir ointment applied 4-6 times per day and mupirocin ointment applied 3 times per day to her breast with resolution of her breast lesions. She was able to continue expressing her breastmilk with the help of a pump and then resumed breastfeeding once her infection was cleared. Her infants recovered after prolonged parenteral antiviral therapy with age-appropriate development at follow-up.


Assuntos
Aciclovir , Antivirais , Encefalite por Herpes Simples , Herpes Simples , Herpesvirus Humano 1 , Mamilos , Humanos , Feminino , Antivirais/uso terapêutico , Antivirais/administração & dosagem , Recém-Nascido , Aciclovir/uso terapêutico , Aciclovir/administração & dosagem , Herpes Simples/diagnóstico , Herpes Simples/tratamento farmacológico , Herpesvirus Humano 1/isolamento & purificação , Encefalite por Herpes Simples/diagnóstico , Encefalite por Herpes Simples/tratamento farmacológico , Valaciclovir/uso terapêutico , Valaciclovir/administração & dosagem , Complicações Infecciosas na Gravidez/diagnóstico , Adulto , Gravidez , Transmissão Vertical de Doenças Infecciosas , Valina/análogos & derivados , Valina/uso terapêutico , Valina/administração & dosagem , Aleitamento Materno
13.
J Virol Methods ; 329: 114994, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38971379

RESUMO

Herpes Simplex Virus Type 1 (HSV-1) is a widespread human pathogen known for causing a spectrum of clinical manifestations, ranging from mild cold sores to severe complications like encephalitis. Understanding the strain-specific variations of HSV-1 is crucial for elucidating its pathogenesis and developing targeted therapeutic interventions. In this multifaceted study, we investigated the strain-specific characteristics of HSV-1 using an in vivo rat model. Firstly, a pilot study was conducted to assess the capacity of three HSV-1 strains (Fisher (F), KOS (K), and MacIntyre (M)) to induce cold sores in rats. Remarkably, the F strain exhibited pronounced pathogenicity, inducing erythema, swelling, and disrupted epidermis with ulceration, distinguishing it from the K and M strains. Subsequently, the treatment capability of intravenous acyclovir injection in HSV-1 F strain-infected rats was evaluated. Acyclovir treatment resulted in a significant reduction in HSV-1 viral copy numbers in serum and dissected neuronal tissues, particularly in the spinal cord, brain, and lower lip. Lastly, whole genome sequencing data revealed that high-impact mutations occurred in the K and M strains within the UL49, US2, and US3 genes. These mutations may play a pivotal role in influencing viral replication, dissemination, pathogenesis, and infectivity. In contrast, the moderate missense variant mutations detected in the US12, US8, UL3, UL30, UL31, and UL36 genes appeared to have no effect on viral pathogenesis and infectivity, based on RT-PCR data for spinal cord, trigeminal nerve, brain, and the lower lip. These strain-specific mutations underscore the dynamic nature of HSV-1 evolution. Collectively, our findings contribute to a deeper understanding of HSV-1 strain diversity and pave the way for the development of targeted therapeutic strategies against this medically significant virus.


Assuntos
Aciclovir , Antivirais , Herpes Simples , Herpesvirus Humano 1 , Sequenciamento de Nucleotídeos em Larga Escala , Animais , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/patogenicidade , Herpesvirus Humano 1/isolamento & purificação , Herpesvirus Humano 1/efeitos dos fármacos , Ratos , Herpes Simples/virologia , Antivirais/farmacologia , Antivirais/uso terapêutico , Aciclovir/farmacologia , Aciclovir/uso terapêutico , Modelos Animais de Doenças , Projetos Piloto , Mutação , Virulência , Genoma Viral , Masculino
15.
Int J Infect Dis ; 147: 107170, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39025201

RESUMO

PURPOSE: Acute retinal necrosis (ARN) is a vision-threatening uveitis caused by herpesviruses reactivation, which has recently been suggested to be associated with COVID-19 infection and after vaccination against it. CASE DESCRIPTION: We present the case of a 58-year-old Japanese woman with ARN in the left eye due to herpes simplex virus 2 (HSV2) two days after receiving the fifth dose of the BNT162b2 mRNA COVID-19 vaccine. The patient demonstrated an ARN history in the right eye and had been treated for it. The patient was administered oral steroids and immunosuppressive drugs for mixed connective tissue disease and organizing pneumonia. The patient was treated with intravenous acyclovir and foscarnet, and a vitrectomy was performed for retinal detachment. The lesion took approximately two months to scar. CONCLUSION: This report suggests that patients with an ARN history might be at risk of ARN recurrence because of the reactivation of the herpes simplex virus induced by COVID-19 vaccination.


Assuntos
Vacina BNT162 , COVID-19 , Herpes Simples , Herpesvirus Humano 2 , Síndrome de Necrose Retiniana Aguda , Ativação Viral , Feminino , Humanos , Pessoa de Meia-Idade , Aciclovir/uso terapêutico , Antivirais/uso terapêutico , Vacina BNT162/efeitos adversos , COVID-19/diagnóstico , Herpes Simples/tratamento farmacológico , Recidiva , Síndrome de Necrose Retiniana Aguda/tratamento farmacológico , Síndrome de Necrose Retiniana Aguda/virologia , Vacinação/efeitos adversos , Vitrectomia
16.
Curr Opin Infect Dis ; 37(5): 413-418, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39079178

RESUMO

PURPOSE OF REVIEW: The American Academy of Pediatrics recently published guidance for the evaluation and management of febrile infants. However, guidance on testing and empiric treatment for neonatal herpes simplex virus (HSV) remains less standardized and subject to clinical practice variation. RECENT FINDINGS: Recent reports reveal that high numbers of infants presenting for sepsis evaluations need to be treated empirically with acyclovir to capture one case of neonatal HSV. Clinical and laboratory risk factors for neonatal HSV identified in the literature can be used for a targeted approach to testing and treating infants for HSV to optimize resource utilization. SUMMARY: The literature supports a targeted approach to evaluation and empiric acyclovir treatment for neonatal HSV, but additional studies are needed to validate this approach given the rarity of disease.


Assuntos
Aciclovir , Antivirais , Herpes Simples , Complicações Infecciosas na Gravidez , Humanos , Herpes Simples/tratamento farmacológico , Herpes Simples/diagnóstico , Recém-Nascido , Antivirais/uso terapêutico , Aciclovir/uso terapêutico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/virologia , Complicações Infecciosas na Gravidez/diagnóstico , Sepse/tratamento farmacológico , Sepse/diagnóstico , Simplexvirus/efeitos dos fármacos , Fatores de Risco
17.
Antiviral Res ; 228: 105950, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38944159

RESUMO

Herpes simplex virus type 1 (HSV-1) is a neurotropic alphaherpesvirus that establishes a lifelong infection in sensory neurons of infected individuals, accompanied with intermittent reactivation of latent virus causing (a)symptomatic virus shedding. Whereas acyclovir (ACV) is a safe and highly effective antiviral to treat HSV-1 infections, long-term usage can lead to emergence of ACV resistant (ACVR) HSV-1 and subsequently ACV refractory disease. Here, we isolated an HSV-1 strain from a patient with reactivated herpetic eye disease that did not respond to ACV treatment. The isolate carried a novel non-synonymous F289S mutation in the viral UL23 gene encoding the thymidine kinase (TK) protein. Because ACV needs conversion by viral TK and subsequently cellular kinases to inhibit HSV-1 replication, the UL23 gene is commonly mutated in ACVR HSV-1 strains. The potential role of the F289S mutation causing ACVR was investigated using CRISPR/Cas9-mediated HSV-1 genome editing. Reverting the F289S mutation in the original clinical isolate to the wild-type sequence S289F resulted in an ACV-sensitive (ACVS) phenotype, and introduction of the F289S substitution in an ACVS HSV-1 reference strain led to an ACVR phenotype. In summary, we identified a new HSV-1 TK mutation in the eye of a patient with ACV refractory herpetic eye disease, which was identified as the causative ACVR mutation with the aid of CRISPR/Cas9-mediated genome engineering technology. Direct editing of clinical HSV-1 isolates by CRISPR/Cas9 is a powerful strategy to assess whether single residue substitutions are causative to a clinical ACVR phenotype.


Assuntos
Aciclovir , Antivirais , Sistemas CRISPR-Cas , Farmacorresistência Viral , Edição de Genes , Herpesvirus Humano 1 , Mutação , Timidina Quinase , Timidina Quinase/genética , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 1/enzimologia , Humanos , Farmacorresistência Viral/genética , Aciclovir/farmacologia , Aciclovir/uso terapêutico , Antivirais/farmacologia , Antivirais/uso terapêutico , Herpes Simples/virologia , Herpes Simples/tratamento farmacológico
18.
BMC Infect Dis ; 24(1): 556, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831304

RESUMO

BACKGROUND: Herpes simplex encephalitis (HSE) is an important central nervous infection with severe neurological sequelae. The aim of this study was to describe clinical characteristic and outcomes of patients with HSE in Vietnam. METHODS: This was a retrospective study of 66 patients with herpes simplex encephalitis who admitted to the National Hospital for Tropical Diseases, Hanoi, Vietnam from 2018 to 2021. The detection of herpes simplex virus (HSV) in cerebrospinal fluid was made by the real-time PCR assay. We reported the clinical manifestation on admission and evaluated clinical outcomes at the hospital discharge by modified Rankin Scale (mRS). Multivariate logistic regression analysis was used to analyze the independent risk factors of severe outcomes. RESULTS: Of the 66 patients with laboratory confirmed HSE, the median age was 53 years (IQR 38-60) and 44 patients (69.7%) were male. The most common manifestations included fever (100%), followed by the consciousness disorder (95.5%). Other neurological manifestation were seizures (36.4%), memory disorders (31.8%), language disorders (19.7%) and behavioral disorders (13.6%). Conventional magnetic resonance imaging (MRI) showed 93.8% patients with temporal lobe lesions, followed by abnormalities in insula (50%), frontal lobe (34.4%) and 48.4% of patients had bilateral lesions. At discharge, 19 patients (28.8%) completely recovered, 15 patients (22.7%) had mild sequelae, 28 patients (42.4%) had moderate to severe sequelae. Severe neurological sequelae were memory disorders (55.8%), movement disorders (53.5%), language disorders (30.2%). Multivariate logistic regression analysis showed that Glasgow score decrement at admission, seizures, and time duration from onset of symptoms to the start of Acyclovir treatment > 4 days were independent factors associated with severe outcomes in HSE patients. CONCLUSION: Glasgow score decrement, seizures and delay treatment with Acyclovir were associated with the poor outcome of patients with HSE.


Assuntos
Encefalite por Herpes Simples , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Vietnã/epidemiologia , Adulto , Encefalite por Herpes Simples/tratamento farmacológico , Encefalite por Herpes Simples/virologia , Encefalite por Herpes Simples/epidemiologia , Antivirais/uso terapêutico , Simplexvirus/isolamento & purificação , Simplexvirus/genética , Fatores de Risco , Imageamento por Ressonância Magnética , Aciclovir/uso terapêutico , Resultado do Tratamento
19.
Nat Commun ; 15(1): 4932, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858365

RESUMO

This study investigates the role of circular RNAs (circRNAs) in the context of Varicella-Zoster Virus (VZV) lytic infection. We employ two sequencing technologies, short-read sequencing and long-read sequencing, following RNase R treatment on VZV-infected neuroblastoma cells to identify and characterize both cellular and viral circRNAs. Our large scanning analysis identifies and subsequent experiments confirm 200 VZV circRNAs. Moreover, we discover numerous VZV latency-associated transcripts (VLTs)-like circRNAs (circVLTslytic), which contain multiple exons and different isoforms within the same back-splicing breakpoint. To understand the functional significance of these circVLTslytic, we utilize the Bacteria Artificial Chromosome system to disrupt the expression of viral circRNAs in genomic DNA location. We reveal that the sequence flanking circVLTs' 5' splice donor plays a pivotal role as a cis-acting element in the formation of circVLTslytic. The circVLTslytic is dispensable for VZV replication, but the mutation downstream of circVLTslytic exon 5 leads to increased acyclovir sensitivity in VZV infection models. This suggests that circVLTslytic may have a role in modulating the sensitivity to antiviral treatment. The findings shed new insight into the regulation of cellular and viral transcription during VZV lytic infection, emphasizing the intricate interplay between circRNAs and viral processes.


Assuntos
Herpesvirus Humano 3 , RNA Circular , RNA Viral , Replicação Viral , RNA Circular/genética , RNA Circular/metabolismo , Herpesvirus Humano 3/genética , Humanos , RNA Viral/genética , RNA Viral/metabolismo , Replicação Viral/genética , Linhagem Celular Tumoral , Latência Viral/genética , Infecção pelo Vírus da Varicela-Zoster/virologia , Aciclovir/farmacologia , Aciclovir/uso terapêutico , Éxons/genética
20.
Infect Dis (Lond) ; 56(10): 842-850, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38822453

RESUMO

BACKGROUND: Systematic treatment with intravenous acyclovir is usually given when varicella zoster virus (VZV) DNA is isolated in cerebrospinal fluid (CSF), indicating central nervous system (CNS) involvement. Our study aimed to describe therapeutic management and acute kidney injury (AKI) occurrence during acyclovir treatment of VZV infection with CNS involvement. METHODS: Multicentre, retrospective study including all patients from 2010 to 2022 with VZV DNA in CSF. Patient management and outcomes were compared according to clinical presentation and indications for intravenous acyclovir: i) definite (encephalitis, myelitis or stroke, peripheral nervous system (PNS) with ≥ 2 roots, herpes zoster ≥ 3 dermatomes, immunosuppression), ii) questionable (1 or 2 dermatomes) or iii) no indication (other situations). RESULTS: 154 patients were included (median age 66 (interquartile range 43-77), 87 (56%) males); 60 (39%) had encephalitis, myelitis or stroke, 35 (23%) had PNS involvement, 37 (24%) had isolated meningitis, 14 (9%) had isolated cutaneous presentation, and 8 (5%) had other presentations. Overall, 128 (83%) received intravenous acyclovir for more than 72 h. AKI occurred in 57 (37%) patients. Finally, 42 (27%) and 25 (16%) patients had respectively no or a questionable indication for intravenous acyclovir, while 29 (69%) and 23 (92%) of them received it for more than 72 h, with AKI in 13 (35%) and 13 (52%) patients, respectively. In-hospital mortality was 12% (n = 18), and no deaths were reported in isolated meningitis. CONCLUSIONS: Intravenous acyclovir is widely prescribed when VZV DNA is isolated in CSF, regardless of the clinical presentation, with a high rate of AKI. Further studies are needed to better define the value of intravenous acyclovir in isolated VZV meningitis.


Assuntos
Injúria Renal Aguda , Aciclovir , Antivirais , Herpesvirus Humano 3 , Humanos , Aciclovir/uso terapêutico , Aciclovir/administração & dosagem , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Injúria Renal Aguda/virologia , Antivirais/uso terapêutico , Antivirais/administração & dosagem , Estudos Retrospectivos , Adulto , Herpesvirus Humano 3/efeitos dos fármacos , Herpesvirus Humano 3/isolamento & purificação , Herpesvirus Humano 3/genética , Infecção pelo Vírus da Varicela-Zoster/tratamento farmacológico , Infecção pelo Vírus da Varicela-Zoster/complicações , Meningite Viral/tratamento farmacológico , Meningite Viral/virologia , Meningite Viral/líquido cefalorraquidiano , Herpes Zoster/tratamento farmacológico , Herpes Zoster/complicações , Herpes Zoster/virologia , DNA Viral/líquido cefalorraquidiano
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