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Microglial GLT-1 is upregulated in response to herpes simplex virus infection to provide an antiviral defence via glutathione.

Herpes simplex virus (HSV) can enter the central nervous system and cause encephalitis (HSV-1) or meningitis (HSV-2). Microglia, the immunocompetent cells of the central nervous system, are potentially able to detect viral infections. Microglia have been shown to express the glutamate transporter GLT-1 during pathological events, leading to increased microglial glutamate uptake and glutathione synthesis. This study aims to address the role of GLT-1 and glutathione, a major antioxidant with antiviral properties, during HSV infections. Using neuron-enriched mixed primary cultures from rat, it wa…

The microenvironment of vulvar skin in women with symptomatic and asymptomatic herpes simplex virus type 2 (HSV-2) infection.

BACKGROUND: It is not known why some individuals infected with herpes simplex virus type 2 (HSV-2), experience frequent recurrences, while most of those infected have a completely silent infection. OBJECTIVE: We wanted to study if local factors in the skin could explain this difference. DESIGn 21 HSV-2 seropositive patients, 10 with history of >8 clinical recurrences a year (symptomatics) and 11 without symptoms of genital herpes (asymptomatics) were included. All had to answer a questionnaire. With standardised methods, the skin temperature, pH, and the skin barrier function, expressed as tr…

Role of T-lymphocyte subsets in facial nerve paralysis owing to the reactivation of herpes simplex virus type 1.

CONCLUSION: Although both T-cell subsets are essential for inhibiting HSV-1 reactivation in the GG, CD4 + T cells play a more important role in host defense against virus replication. OBJECTIVE: To elucidate the host immunological factors that participate in herpes simplex virus type 1 (HSV-1) reactivation in the geniculate ganglia (GG) and lead to facial paralysis, we developed a mouse model of facial paralysis that involved the reactivation of HSV-1 following general immune suppression. MATERIAL AND METHODS: Eight weeks after recovery from primary facial paralysis caused by inoculating the…

The epidemiology of genital infection with herpes simplex virus types 1 and 2 in genitourinary medicine attendees in inner London.

OBJECTIVE: To characterise the epidemiological and clinical features of genital herpes and the diagnostic role of HSV-2 specific serology in an ethnically diverse cohort of genitourinary medicine (GUM) attendees in inner London. METHODS: Genital swabs (n = 186) were tested by real time polymerase chain reaction (PCR) and serum samples (n = 70) by HSV-2 specific enzyme linked immunoassay (ELISA). RESULTS: Among 186 patients (median age 29 years), 104/186 (56%) were male and 176/186 (95%) heterosexual; ethnicity was predominantly black Caribbean (76/186, 41%), white (65/186, 35%), or black-Afr

Detection, quantification and genotyping of Herpes Simplex Virus in cervicovaginal secretions by real-time PCR: a cross sectional survey.

BACKGROUND: Herpes Simplex Virus (HSV) Genital Ulcer Disease (GUD) is an important public health problem, whose interaction with HIV results in mutually enhancing epidemics. Conventional methods for detecting HSV tend to be slow and insensitive. We designed a rapid PCR-based assay to quantify and type HSV in cervicovaginal lavage (CVL) fluid of subjects attending a Genito-Urinary Medicine (GUM) clinic. Vaginal swabs, CVL fluid and venous blood were collected. Quantitative detection of HSV was conducted using real time PCR with HSV specific primers and SYBR Green I. Fluorogenic TaqMan Minor Gro…

Herpes simplex virus bullous keratitis misdiagnosed as a case of pseudophakic bullous keratopathy with secondary glaucoma: an unusual presentation.

PURPOSE: To report an unusual case of herpetic bullous keratitis misdiagnosed as a case of pseudophakic bullous keratopathy with secondary g … rnea during a subsequent visit four days later. Virological investigations confirmed a diagnosis of Herpes simplex keratitis. He was treated with topical acyclovir. CONCLUSIONS: This case highlights the fact that herpes simplex keratitis can present initially as a more diffuse corneal stromal and epithelial edema with epithelial bullae mimicking bullous keratop …

Evaluation of a peptidomimetic ribonucleotide reductase inhibitor with a murine model of herpes simplex virus type 1 ocular disease.

The ribonucleotide reductase (RR) of herpes simplex virus type 1 (HSV-1) is an important virulence factor, being required for neurovirulence, ocular virulence, and reactivation from latency. The RR activity requires the association of two distinct homodimeric subunits, and the association of the subunits is inhibited in the presence of a peptide homologous to the carboxy terminus of the small subunit. A structural analog of the inhibitory peptide (BILD 1263) has been shown to inhibit the replication of HSV-1 at micromolar concentrations in vitro. We used a mouse model of HSV-1 ocular infection…

A follow-up study of children with neonatal herpes simplex virus infections with particular regard to late nervous disturbances.

Forty-five children with neonatal herpes simplex virus (HSV) infection, representing all known cases in the diagnostic records of four virological laboratories within a 15-year period, were followed up. Twelve children had died. Sixteen of the 33 survivors were healthy. Thirteen children had severe disabilities: all of them showed severe mental retardation; moreover, 11 were tetraplegic, one was hemiplegic with hydrocephalus and one had a pronounced behavioural abnormality. Four children had slight to moderate disabilities: one child was mildly mentally retarded and three, although mentally no…

A cross-sectional study of herpes simplex virus types 1 and 2 in college students: occurrence and determinants of infection.

Occurrence rates and determinants of infection with herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) were measured in first- and fourth-year undergraduate students at a state university. This cross-sectional multistage probability sample survey included sociodemographic characteristics, sexual behavior patterns, disease history, and HSV type-specific antibody status. The prevalence of HSV-1 antibody was 37.2% in freshmen and 46.1% in fourth-year students; that for HSV-2 antibody was 0.4% and 4.3%, respectively. A history of cold sores was obtained in 25.6% of the freshmen; none had a histo…

Paradoxical effects of interferon on reactivation of oral infection with herpes simplex virus after microvascular decompression for trigeminal neuralgia.

Fifty-five patients undergoing microvascular decompression for trigeminal neuralgia were divided into three groups in a two-stage placebo-controlled study. All groups received two injections a day for five days beginning the day before surgery. Twenty-one patients received 10 placebo injections, 11 in the presurgical treatment group received three injections of 3.5 X 10(4) units of leukocyte interferon/kg before surgery, and 23 in the postsurgical treatment group received seven injections after surgery. The remaining injections in the two treatment groups were placebos. In the first stage, wit

Thermolabile in vivo DNA-binding activity associated with a protein encoded by mutants of herpes simplex virus type 1.

The major DNA-binding protein encoded by several temperature-sensitive mutants of herpes simplex virus type 1 was thermolabile for binding to intracellular viral DNA. The ability of DNase I to release this protein from isolated nuclei was used as a measure of the amount of protein bound to viral DNA. This assay was based upon our previous observation that the fraction of herpesviral DNA-binding protein which can be eluted from nuclei with DNase I represents proteins associated with progeny viral DNA (D. M. Knipe and A. E. Spang, J. Virol. 43:314-324, 1982). In this study, we found that several…

The pathogenesis and pathway into the central nervous system after intraocular infection of herpes simplex virus type I in rabbits.

Herpes simplex virus (HSV) type I was injected into the right eye of 18-day-old New Zealand albino rabbits and the animals were killed on the fourth and eighth days after inoculation. Longitudinal section of the optic nerves and chiasma showed that both myelinated axons and neuroglial cells crossed at the chiasma. Semi-serial (1 micrometer) and ultrathin sections showed the presence of HSV in both astrocytes and oligodendrocytes, although no particles were seen in the myelinated axons; the infected cells were confined to the medial side of the right optic nerve. HSV travels centropetally along…

Inhibition of herpes simplex virus by synthetic double-stranded RNA (polyriboadenylic and polyribouridylic acids and polyriboinosinic and polyribocytidylic acids).

Two-stranded polyriboadenylic and polyribouridylic acids and polyriboinosinic and polyribocytidylic acids protect against herpes simplex virus-induced cytopathogenicity in HEp 2 cultures, systemic herpes simplex virus infection in mice, and herpes simplex virus-induced keratoconjunctivitis in rabbits.

[Immunogenic activity of temperature sensitive mutation of herpes simplex virus type-1 in mono- and polyvalent conditions with different attenuated strains of virus. II. Analysis of humoral immunologic response induced by mutants of temperature sensitive herpes simplex type-1 virus in polyvalent systems].

The ability of mutant ts HSV-1 on 45 passage to induction of IgG antibody response in the presence of other attenuated viral strain, like measles, mumps, rubella was evaluated, and the effect of mutant ts HSV-1 on humoral immunity induced by attenuated measles and mumps strains was also tested. The obtained results clearly indicated that even immunization with other RNA virus strains had no effect on IgG antibody response to mutant ts HSV-1. Significant differences were observed in IgG antibody responses to mumps and measles between groups of guinea pigs immunized with these viruses alone or t

Herpes simplex virus type-1 infection and spread in a novel porcine corneal explant model is restricted to the epithelium.

Herpes Keratitis (HK) is a debilitating infection of the cornea that remains the leading cause of infectious blindness in developed countries. Caused primarily by herpes simplex virus type 1 (HSV-1), it is associated with recurrent inflammation, leading to corneal scarring. This study investigated the initial events during acute HSV-1 infection in the cornea by adapting our human anogenital mucosal explant model to a HSV-1 infected porcine corneal explant model. We infected these corneas topically via high-density microarray patches (HD-MAPs) dipped in GFP-labelled HSV-1. Virus infection and s…

Discovery of a Baloxavir-Inspired Endonuclease Inhibitor That Prevents Herpes Simplex Virus 1 Replication in Cell Culture and In Vivo.

Herpes simplex viruses (HSV-1 and HSV-2) are highly prevalent and contagious, causing lifelong infections that cannot be eradicated with current therapies. Acyclovir and other viral DNA polymerase inhibitors are effective antiviral agents for treating HSV infections. However, despite the recent approval of pritelivir and amenamevir (helicase-primase complex inhibitors), drug resistance is still a major threat to therapeutic success. This research focuses on developing new antiviral strategies against HSV-1 by targeting the pUL15 endonuclease, a component of the viral packaging motor/terminase …

Discovery of Phloroglucinol Derivatives as a New Type of Nonnucleoside Inhibitors with Anti-herpes Simplex Virus Type 1 Activity.

Herpes simplex virus type 1 (HSV-1) causes keratoconjunctivitis and encephalitis, with nucleoside analogues such as acyclovir (ACV) serving as standard treatments. However, rising drug resistance underscores the need for agents with novel mechanisms. In this study, phytochemical investigation led to the obtainment of several phloroglucinol derivatives from Rhodomyrtus tomentosa. Subsequent phenotypic screening demonstrated compound 6 as the most promising HSV-1 inhibitor. To facilitate lead optimization, we synthesized 44 analogues of 6 to elucidate the structure-activity relationships, and 24…

:: Обновление информации о мутации резистентности и последствиях для клинического управления с помощью вируса simpex и лекарственной резистентности.

КОЛИЧЕСТВО: Сопротивление антивирусным лекарственным препаратам в герпесах с простейшим вирусом 1 и 2 (HSV-1 и 2) является серьезной клинической проблемой, особенно у больных с иммунокомпромиссированными заболеваниями. Тестирование на зависимость от наркотиков (DST) помогает клиническому управлению и может проводиться с использованием методов генотипического (частичной последовательности генома) или фенотипического (клеоточной культуры). У обоих есть присущие им ограничения: генотипический DST ограничен устаревшими наборами данных, не имеющими информации о новых ингибиторах гелиопатии-примаса

Совпадение в аннотации оригинала
BACKGROUND: Antiviral drug resistance in herpes simplex virus 1 and 2 (HSV-1 and 2) is a significant clinical challenge, particularly in immunocompromised patients. Drug susceptibility testing (DST) aids clinical management and can be conducted through genotypic (partial genome sequencing) or phenotypic (cell culture) methods. Both have inherent limitations:…