UNASSIGNED: Oral herpes infections caused by herpes simplex virus type 1 (HSV-1) are one of the most common in the human population. Recently, they have been classified as an increasing problem in immunocompromised patients and those suffering from chronic inflammation of the oral mucosa and gums. Treatment mainly involves nucleoside analogues, such as acyclovir and its derivatives, which reduce virus replication and shedding. As drug-resistant strains of herpes emerge rapidly, there is a need for the development of novel anti-herpes agents. The aim of the study was to design an antiviral peptide, based on natural compounds, non-toxic to the host, and efficient against drug-resistant HSV-1. Here, we designed a lysine-rich derivative of amphibian temporin-1CEb conjugated to peptides penetrating the host cell membrane and examined their activity against HSV-1 infection of oral mucosa.
UNASSIGNED: We assessed the antiviral efficiency of the tested compound in simple 2D cell models (VeroE6 and TIGKs cells) and a 3D organotypic model of human gingiva (OTG) using titration assay, qPCR, and confocal imaging. To identify the molecular mechanism of antiviral activity, we applied the Azure A metachromatic test, and attachment assays techniques. Toxicity of the conjugates was examined using XTT and LDH assays.
UNASSIGNED: Our results showed that temporin-1CEb analogues significantly reduce viral replication in oral mucosa. The mechanism of peptide analogues is based on the interaction with heparan sulfate, leading to the reduce attachment of HSV-1 to the cell membrane. Moreover, temporin-1CEb conjugates effectively penetrate the gingival tissue being effective against acyclovir-resistant strains. Collectively, we showed that temporin-1CEb can be regarded as a novel, naturally derived antiviral compound for HSV-1 treatment.

Previous exposure to Epstein-Barr virus (EBV) is strongly associated with the development of multiple sclerosis (MS). By contrast, past cytomegalovirus (CMV) infection may have no association, or be negatively associated with MS. This study aimed to investigate the associations of herpesvirus infections with MS in an Italian population. Serum samples (n = 200) from Italian people with multiple sclerosis (PwMS) classified as the relapsing-and-remitting clinical phenotype and (n = 137) healthy controls (HCs) were obtained from the CRESM Biobank, Orbassano, Italy. Both PwMS and HCs samples were selected according to age group (20-39 years, and 40 or more years) and sex. EBV virus capsid antigen (VCA) IgG, EBV nucleic acid-1 antigen (EBNA-1) IgG, CMV IgG, herpes simplex virus (HSV) IgG, and varicella zoster virus (VZV) IgG testing was undertaken using commercial ELISAs. EBV VCA IgG and EBNA-1 IgG seroprevalences were 100% in PwMS and 93.4% and 92.4%, respectively, in HCs. EBV VCA IgG and EBNA-1 IgG levels were higher (p < 0.001) in PwMS compared with HCs. For PwMS, the EBNA-1 IgG levels decreased with age, particularly in females. The CMV IgG seroprevalence was 58.7% in PwMS and 62.9% in HCs. CMV IgG seroprevalence increased with age. The HSV IgG seroprevalence was 71.2% in PwMS and 70.8% in HCs. HSV IgG levels were lower (p = 0.0005) in PwMS compared with HCs. VZV IgG seroprevalence was 97.5% in PwMS and 98.5% in HCs. In the population studied, several herpesvirus infections markers may have been influenced by the age and sex of the groups studied. The lack of a negative association of MS with CMV infection, and the observation of lower levels of HSV IgG in PwMS compared with HCs are findings worthy of further investigation.

Herpes simplex encephalitis (HSVE) is a potentially fatal infectious central nervous system (CNS) disorder. Thus, early detection is critical in determining the case\'s fate. Clinical history and examination, brain computed tomography, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and lumbar puncture have been used to establish a diagnosis. This report describes a case of HSVE with hypocellular cerebrospinal fluid (CSF) and an uncommon form of memory impairment. However, MRI results were consistent with HSVE, and CSF PCR tested positive for HSV-1 DNA that responded to treatment. We routinely advise patients to begin antiviral therapy as soon as possible to avoid complications.

A 33-year-old female was admitted for community-acquired pneumonia. On presentation, she was tachypneic and tachycardic and leukocytosis at 28,900/µL. Chest imaging showed dense consolidation on the right upper lobe. Due to refractory worsening respiratory failure, she was intubated with mechanical ventilation. Initial bronchoscopy with culture data was negative. Extracorporeal membrane oxygenation was pursued on the fourth day. Repeat bronchoscopy revealed targetoid ulcerative lesions with erythema in the right middle, lower lobes and left lower lobe. We describe a case of herpes simplex virus pneumonia in an immunocompetent patient that occurred in the setting of acute bacterial infection.

UNASSIGNED: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease characterized by excessive immune activation. It is more commonly seen in children but increasingly recognized in adults. Primary HLH relies on a genetic predisposition, whereas secondary HLH develops in the context of infections, malignancies, or autoimmune diseases. Hemophagocytic lymphohistiocytosis has been rarely described in patients on immunosuppressive therapy after kidney transplant. Here, we describe a case of HLH in a patient with a remote history of kidney transplant, triggered by a viral infection.
UNASSIGNED: A 45-year-old female, with a kidney transplant in 2009 for IgA nephropathy, presented with fever, vomiting, and back pain of 1-week duration. She was on triple immunosuppression consisting of daily doses of prednisone 5 mg, azathioprine 100 mg, and tacrolimus extended release 1 mg, and a baseline creatinine of 130 µmol/L.
UNASSIGNED: Initial investigations showed anemia, leukopenia, elevated serum creatinine, transaminitis, and markedly increased ferritin of 67 600 µg/L which prompted a bone marrow biopsy to rule out HLH. The bone marrow showed an increased proportion of CD68+ cells (macrophages) with more than 5 in 1000 hemophagocytic macrophages. Her soluble IL-2 receptor (CD25) level was 3406 pg/mL (606-2299 pg/mL) which was mildly elevated. She fulfilled 4 of the 8 criteria for HLH and with an H score was 223 which suggested a diagnosis of HLH with 96.9% probability. An extensive secondary workup for possible triggers for HLH led to a swab from genital ulcers that was positive for herpes simplex virus (HSV) type 2. The polymerase chain reaction (PCR) in the blood for HSV type 2 was also positive.
UNASSIGNED: Given the diagnosis of HSV type 2 as the putative trigger for HLH, she was started on parenteral acyclovir for 2 weeks followed by oral valacyclovir for 2 more weeks. In the context of infection, the azathioprine was stopped while low-dose steroid and tacrolimus were continued.
UNASSIGNED: With the initiation of treatment for HSV infection, leukopenia, creatinine, and transaminases improved along with ferritin levels. At her 6-month follow-up, her blood counts and liver enzymes had normalized, and ferritin was 566 µg/L.
UNASSIGNED: Hemophagocytic lymphohistiocytosis is a rare disease in kidney transplant recipients with a high mortality rate. It can occur even in remote kidney transplant recipients so a high degree of suspicion is necessary to lead to a prompt diagnosis. Infections are common triggers for secondary HLH. Early identification and treatment of the triggering infection may improve outcomes.
UNASSIGNED: La lymphohistiocytose hémophagocytaire (HLH) est une maladie potentiellement mortelle caractérisée par une activation excessive du système immunitaire. Elle est plus fréquente chez les enfants, mais de plus en plus observée chez les adultes. La HLH primaire se manifeste en raison d’une prédisposition génétique, tandis que la HLH secondaire se développe dans le contexte d’une infection, d’un cancer ou d’une maladie auto-immune. La HLH a rarement été décrite chez les patients sous traitement immunosuppresseur à la suite d’une transplantation rénale. Nous présentons un cas de HLH déclenché par une infection virale chez une patiente avec des antécédents lointains de transplantation rénale.
UNASSIGNED: Une femme de 45 ans, greffée du rein en 2009 en raison d’une néphropathie à IgA, a consulté pour de la fièvre, des vomissements et des douleurs dorsales depuis une semaine. Son triple traitement immunosuppresseur consistait en des doses quotidiennes de prednisone (5 mg), d’azathioprine (100 mg) et de tacrolimus à libération prolongée (1 mg). Son taux de créatinine usuel était de 130 umol/L.
UNASSIGNED: Les premières investigations ont révélé une anémie, de la leucopénie, un taux de créatinine sérique élevé, une transaminite et un taux de ferritine nettement élevé de 67 600 ug/L, ce qui a justifié une biopsie de la moelle osseuse pour exclure une HLH. Les résultats ont montré une plus grande proportion de cellules CD68+ (macrophages), avec plus de 5 macrophages hémophagocytaires sur 1000. Le taux de récepteurs solubles de l’IL-2 (CD25) s’établissait à 3 406 pg/ml (606 à 2 299 pg/ml), ce qui est légèrement élevé. La patiente répondait à quatre des huit critères de la HLH et présentait un score H de 223, ce qui suggérait une probabilité de 96,9 % pour un diagnostic de HLH. L’examen secondaire approfondi des possibles déclencheurs de la HLH a inclus un prélèvement sur des ulcères génitaux qui s’est avéré positif pour le virus de l’herpès simplex (HSV) de type 2. La PCR d’échantillons sanguins était également positive pour HSV de type 2.
UNASSIGNED: L’infection par HSV de type 2 ayant été identifiée comme le déclencheur présumé de la HLH, la patiente a reçu un traitement parentéral d’acyclovir pendant deux semaines, suivi d’un traitement oral de valacyclovir pour deux semaines supplémentaires. Dans le contexte de l’infection, l’azathioprine a été cessée, mais le tacrolinus et les stéroïdes à faible dose ont été maintenus.
UNASSIGNED: L’amorce du traitement antiviral a entraîné une amélioration de la leucopénie, du taux de créatinine et des transaminases, ainsi que des taux de ferritine. Lors du dernier suivi à 6 mois, la numérisation sanguine et les enzymes hépatiques de la patiente s’étaient normalisées et son taux de ferritine était de 566 ug/L.
UNASSIGNED: La lymphohistiocytose hémophagocytaire est une maladie rare chez les greffés rénaux et elle entraîne un taux élevé de mortalité. La maladie peut survenir même chez des greffés rénaux de longue date, de sorte qu’il est nécessaire d’exercer un degré élevé de vigilance afin de poser rapidement un diagnostic. Les infections sont de fréquents déclencheurs de la HLH secondaire. Les résultats peuvent être améliorés par l’identification et le traitement précoces de l’infection ayant déclenché la maladie.

The skin is a complex tissue that provides a strong physical barrier against invading pathogens. Despite this, many viruses can access the skin and successfully replicate in either the epidermal keratinocytes or dermal immune cells. In this review, we provide an overview of the antiviral T cell biology responding to cutaneous viral infections and how these responses differ depending on the cellular targets of infection. Much of our mechanistic understanding of T cell surveillance of cutaneous infection has been gained from murine models of poxvirus and herpesvirus infection. However, we also discuss other viral infections, including flaviviruses and papillomaviruses, in which the cutaneous T cell response has been less extensively studied. In addition to the mechanisms of successful T cell control of cutaneous viral infection, we highlight knowledge gaps and future directions with possible impact on human health.

Herpes simplex virus (HSV) is a common cause of recurrent oropharyngeal ulcers or stomatitis resulting from the reactivation of latent infection since childhood. Extensive ulceration and dissemination to vital organs such as pneumonitis or colitis is mostly encountered among hematologic malignancy or hematologic stem cell transplants. We hereby reported a case with osteosarcoma who developed disseminated HSV infection during neutropenia after chemotherapy.

Background/Objectives: Cidofovir, an antiviral drug approved for cytomegalovirus retinitis, has emerged as an alternative treatment option for virally induced cutaneous and mucocutaneous conditions, as well as being trialed as a treatment for select neoplasms. In this review, we highlight the existing evidence, clinical uses, and rationale of using cidofovir for the treatment of cutaneous pathologies. Methods: A PubMed database literature search was conducted to identify relevant articles for inclusion in this review. Results: Cidofovir has several cutaneous applications in various formulations including intravenous, topical, and subcutaneous administrations. Primarily through case reports, case series, and retrospective reviews, cidofovir has demonstrated efficacy in treating a variety of virally induced conditions-verruca vulgaris, herpes simplex virus, molluscum contagiosum-as well as in adjuvant treatment for select neoplasms. The drug has shown efficacy in immunocompromised and immunocompetent adults and children alike. Conclusions: The body of literature supports the use of cidofovir as an effective and well-tolerated treatment for many viral cutaneous pathologies, and encourages further study for its use as an adjuvant therapy for neoplastic disease.

UNASSIGNED: Kaposi\'s varicelliform eruption (KVE), also known as eczema herpeticum or eczema vaccinatum, is an acute dermatosis that affects patients with chronic dermatopathies. The diagnosis is primarily clinical and is characterised by the presence of a vesicular exanthema on physical examination. The exanthema subsequently evolves into crusted lesions with typical circular ulcerations in \'punched-out\' areas on the skin affected by the underlying dermatopathy.
UNASSIGNED: We present the case of a 6-year-old patient who presented to the Paediatric Emergency department with skin lesions consistent with eczema herpeticum. The patient\'s management was initially outpatient; however, due to the slow progression of the condition, hospitalisation and intravenous antiviral treatment were initiated.
UNASSIGNED: KVE affects patients with chronic dermatoses, especially atopic dermatitis. It is important to know the clinical presentation for an early suspicion. KVE is a medical emergency that requires prompt diagnosis and treatment. It can progress to secondary viraemia, which can be fatal in up to 10% of immunocompetent individuals and up to 50% of immunocompromised individuals. It is important to be aware of this condition and to start early treatment with antivirals, especially given the high prevalence of atopic dermatitis in our population. This condition is one of the most serious complications that can occur in these patients.
CONCLUSIONS: To facilitate early suspicion and diagnosis, disseminate information about eczema vaccinatum.Emphasise the importance of initiating antiviral treatment early to prevent potential complications of eczema herpeticum.If left untreated, Kaposi\'s varicelliform eruption can result in up to a 10% mortality rate in immunocompetent individuals and a 50% mortality rate in those who are immunocompromised.

Viral modifications enabling syncytium formation in infected cells can augment lysis by oncolytic herpes simplex viruses (oHSVs) which selectively kill cancer cells. In the case of receptor-retargeted oHSVs (RR-oHSVs) that exclusively enter and spread to cancer cells, anti-tumor effects can be enhanced in a magnitude of >100,000-fold by modifying the virus to a syncytial type (RRsyn-oHSV). However, when syncytia containing non-cancerous cells are induced by conditionally replicating syncytial oHSV (CRsyn-oHSV), syncytial death occurs at an early stage. This results in limited anti-tumor effects of the CRsyn-oHSV. Here, we investigated whether necroptosis is involved in death of the syncytia formed by the fusion of cancer cells and non-cancerous cells. Mixed-lineage kinase domain-like (MLKL), a molecule executing necroptosis, was expressed in all murine cancer cell lines examined, while receptor-interacting protein kinase 3 (RIPK3), which phosphorylates MLKL, was absent from most cell lines. In contrast, RIPK3 was expressed in non-cancerous murine fibroblast cell lines. When a CRsyn-oHSV-infected RIPK3-deficient cancer cell line was co-cultured with the fibroblast cell line, but not with the cancer cells themselves, MLKL was phosphorylated and syncytial death was induced. These results indicate that early necroptosis is induced in multinucleated giant cells formed by CRsyn-oHSV when they also contain non-cancerous cells.