AAV2 can replicate its DNA by a rolling hairpin or rolling circle mechanism, depending on the helper virus.

Adeno-associated virus type 2 (AAV2) is a small, non-pathogenic, helper virus-dependent parvovirus with a single-stranded (ss) DNA genome of approximately 4.7 kb. AAV2 DNA replication requires the presence of a helper virus such as adenovirus type 5 (AdV5) or herpes simplex virus type 1 (HSV-1) and is generally assumed to occur as a strand-displacement rolling hairpin (RHR) mechanism initiated at the AAV2 3' inverted terminal repeat (ITR). We have recently shown that AAV2 replication supported by HSV-1 leads to the formation of double-stranded head-to-tail concatemers, which provides evidence for a rolling circle replication (RCR) mechanism. We have revisited AAV2 DNA replication and specifically compared the formation of AAV2 replication intermediates in the presence of either HSV-1 or AdV5 as the helper virus. The results confirmed that the AAV2 DNA replication mechanism is helper virus-dependent and follows a strand-displacement RHR mechanism when AdV5 is the helper virus and primarily an RCR mechanism when HSV-1 is the helper virus. We also demonstrate that recombination plays a negligible role in AAV2 genome replication. Interestingly, the formation of high-molecular-weight AAV2 DNA concatemers in the presence of HSV-1 as the helper virus was dependent on an intact HSV-1 DNA polymerase. IMPORTANCE: AAV is a small helper virus-dependent, non-pathogenic parvovirus. The AAV genome replication mechanism was extensively studied in the presence of AdV as the helper virus and described to proceed using RHR. Surprisingly, HSV-1 co-infection facilitates RCR of the AAV2 DNA. We directly compared AdV5 and HSV-1 supported AAV2 DNA replication and showed that AAV2 can adapt its replication mechanism to the helper virus. A detailed understanding of the AAV replication mechanism expands our knowledge of virus biology and can contribute to increase gene therapy vector production.

A fur plucking model to study herpes simplex virus reactivation and recurrent disease.

Herpes simplex viruses (HSV-1 and HSV-2) most commonly cause ulcerative epithelial lesions (cold sores and genital herpes). Importantly, HSV establishes life-long persistent (latent) infection in peripheral neurons. Reactivation from latency produces recurrent epithelial lesions, which constitute the greatest burden of HSV disease in people. The mechanisms that regulate latency and reactivation remain incompletely understood, in part due to limitations in the animal models available for studying HSV reactivation. We have developed a simple and tractable model to induce HSV-1 and HSV-2 reactivation from latency to cause recurrent skin disease. We infected C57BL/6 mice with HSV-1 (strains NS, F, SC16, 17syn+) or HSV-2 (strain 333) on flank skin depilated by manual plucking. After at least 35 days post-infection (dpi), we replucked the fur from the infected flank and observed recurrent lesions in the same dermatome as the primary infection. We detected HSV DNA in dermatome skin through 4 days post-replucking and observed viral antigen and reporter signal in skin lesions by histology, consistent with viral replication following reactivation. In addition to C57BL/6 mice, we were able to produce reactivation in Balb/c and SKH-1 mice. We found that shaving the ipsilateral flank or plucking the contralateral flank did not induce recurrent skin lesions, suggesting that fur plucking is a specific stimulus that induces HSV reactivation. Furthermore, we were able to induce multiple rounds of plucking-induced recurrent disease, providing a model to investigate the lifelong nature of HSV infection. This new model provides a tractable system for studying pathogenic mechanisms of and therapeutic interventions against HSV reactivation and recurrent disease. IMPORTANCE: Herpes simplex viruses (HSV-1 and HSV-2) have infected over half of the US adult population to cause a lifelong, persistent infection; however, our understanding of the mechanisms that govern HSV reactivation and recurrent disease is incomplete. This is in part due to limitations in the animal models used to study recurrent disease, which are laborious and inefficient in mice. To address this technical gap, we developed a mouse model in which fur plucking after flank skin infection is sufficient to induce episodes of HSV reactivation and recurrent disease. Our work provides a model for the field to investigate the pathogenic mechanisms of HSV and immune responses during recurrent disease and provides an opportunity to investigate the neurobiology of HSV infection.

Herpes Simplex Virus Type-2 Nephritis: An Unexpected Plot Twist in a Kidney Transplant Recipient.

Infections remain an important cause of morbidity in kidney transplant recipients, particularly in the early post-transplant period. This window coincides with an increased risk of acute rejections. Prompt identification of the cause of graft dysfunction is paramount to ensure good outcomes. This case report presents a 32-year-old male undergoing his second living-related kidney transplantation, complicated by herpes simplex virus-2 (HSV-2) nephritis. Despite favorable initial graft function, he developed odynophagia post-operatively, leading to the diagnosis of HSV-related esophageal ulcers. Subsequent acute graft dysfunction prompted biopsy, revealing HSV-2-related acute tubular injury. Prompt initiation of intravenous acyclovir resulted in graft recovery. This case underscores the importance of considering uncommon viral etiologies in post-transplant complications and highlights the role of timely diagnosis and treatment in preserving graft function.

Evolution of Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits Over a Decade.

Infections remain an important cause of morbidity in kidney transplant recipients, particularly in the early post-transplant period. This window coincides with an increased risk of acute rejections. Prompt identification of the cause of graft dysfunction is paramount to ensure good outcomes. This case report presents a 32-year-old male undergoing his second living-related kidney transplantation, complicated by herpes simplex virus-2 (HSV-2) nephritis. Despite favorable initial graft function, he developed odynophagia post-operatively, leading to the diagnosis of HSV-related esophageal ulcers. Subsequent acute graft dysfunction prompted biopsy, revealing HSV-2 related acute tubular injury. Prompt initiation of intravenous acyclovir resulted in graft recovery. This case underscores the importance of considering uncommon viral etiologies in post-transplant complications and highlights the role of timely diagnosis and treatment in preserving graft function.

Seronegative herpes simplex virus (HSV) encephalitis causing temporal lobe epilepsy resulting in new-onset psychosis: a case report and literature review.

Background: Herpes simplex virus (HSV) encephalitis is the most common nonepidemic encephalitis and can result in temporal lobe necrosis. Inflammation of the temporal lobe can result in temporal lobe epilepsy which is known to cause psychiatric symptoms. Case Description: We describe the case of a geriatric male patient who was admitted for new-onset visual hallucinations and other neuropsychiatric symptoms which began five days prior to admission. His lab work was unremarkable, and a computed tomography (CT) scan of the brain demonstrated small vessel ischemic disease. There was clinical suspicion for seizures, and electroencephalogram (EEG) monitoring showed focal seizure activity in the right hemisphere. He received a brain magnetic resonance imaging (MRI) which was suspicious for encephalitis. Various etiologies were considered, and he received an extensive workup including cerebrospinal fluid evaluation. Ultimately, he improved with empiric antiviral treatment added alongside multiple antiepileptic agents. The seizure control and resolution of symptoms with antiviral treatment, in addition to the findings of his central nervous system (CNS) workup, confirmed the presumptive diagnosis of HSV encephalitis. Conclusions: Understanding the multifactorial causes of neuropsychiatric symptoms is important in determining an appropriate workup. The acute onset of specific symptoms in our patient increased suspicion for a structural neurological process. His initial presentation could largely be explained by the vascular dementia and epileptiform activity that were discovered during hospitalization. However, his refractory seizures were suggestive of another underlying etiology. The localization of his seizures and MRI findings were suggestive of HSV encephalitis despite negative HSV polymerase chain reaction (PCR). A patient may benefit from antiviral treatment when the clinical picture is consistent with HSV encephalitis even in the setting of negative serological studies. Clinicians should also be mindful of false negatives on serological tests.

An uncommon combination: a case report of herpes simplex virus encephalitis induced takotsubo cardiomyopathy.

Background: Takotsubo cardiomyopathy, also known as stress-induced cardiomyopathy or broken-heart syndrome, is a non-ischemic cardiomyopathy that presents as a transient regional systolic dysfunction of the left ventricle with minimal increase in troponins. The pathogenesis of takotsubo cardiomyopathy is not well understood. Some possible theories include increased catecholamines causing sympathetic overdrive, microvascular dysfunction, coronary spasm, or inflammation. The association of herpes simplex virus (HSV) encephalitis with takotsubo cardiomyopathy has rarely been reported with only two cases being described in literature. Case Description: We present a patient that came in with altered mental status who was found to have herpes simplex virus 1 (HSV-1) encephalitis. During his hospital stay, the patient had developed shortness of breath on hospital day 3. The patient's troponin was found to be mildly elevated and echocardiogram revealed takotsubo cardiomyopathy with left ventricle ejection fraction (LVEF) of 20% and severe hypokinesis of all left ventricle segments except the basal segments. His echocardiogram nine months prior revealed a LVEF 60-65%. He was treated with intravenous (IV) acyclovir and repeat echocardiogram three weeks following hospitalization revealed resolution of his takotsubo cardiomyopathy. Conclusions: Physicians should keep HSV encephalitis induced takotsubo cardiomyopathy in their differential diagnosis when patients present with HSV encephalitis along with shortness of breath and pulmonary vascular congestion on imaging.

Acupuncture improves spatial learning and memory impairment caused by herpes simplex virus type-1 in rats through the p38 MAPK/CREB pathway.

BACKGROUND: Acupuncture can improve herpes simplex encephalitis (HSE), but the underlying mechanism is not clear. Therefore, we evaluated the cognitive function and apoptosis in hippocampus caused by herpes simplex virus type-1 (HSV-1) in rats after acupuncture and described the molecular mechanism. METHODS: Sprague-Dawley rats were induced into HSE models by HSV-1 infection. After 3 days, they received acupuncture at the acupoints of Xuanzhong (GB39), Baihui (GV20), Shenmen (HT7), Shenting (GV24), and Sanyinjiao (SP6), and/or intraperitoneal injection of the p38 MAPK inhibitor SB203580. Morris water maze test was performed on rats. The hippocampus of rats was obtained, and the expression of apoptosis-related genes in the tissues was detected by qRT-PCR. In addition, apoptosis-related proteins and proteins related to the p38 MAPK/CREB pathway in the tissues was detected by western blot. RESULTS: After HSV-1 induction, the rat's escape latency was increased, the time spent on the platform in the target quadrant and the number of platform crossings significantly decreased. In addition, there was an increase in apoptosis in the hippocampus, accompanied by elevated levels of p-p38 and decreased levels of p-CREB. However, these effects could be improved by acupuncture treatment. Interestingly, SB203580 plays a similar role to acupuncture, and acupuncture could further enhance the impacts of SB203580 on cognitive function and apoptosis in hippocampus in HSE rats. CONCLUSION: Acupuncture improves spatial learning and memory impairment caused by HSV-1 in rats. The functional mechanism of acupuncture may be through the p38 MAPK/CREB pathway.

The antimicrobial protein RNase 7 directly restricts herpes simplex virus infection of human keratinocytes.

Approximately 22% of moderately to severely affected atopic dermatitis (AD) patients have a history of eczema herpeticum, a disseminated rash primarily caused by herpes simplex virus type 1 (HSV-1). Reduced activity of antimicrobial peptides may contribute to the increased susceptibility of AD patients to HSV-1. We previously demonstrated that the antimicrobial protein RNase 7 limits HSV-1 infection of human keratinocytes by promoting self-DNA sensing. Here, we addressed whether RNase 7 has any effect on HSV-1 infection when infecting keratinocytes without exogenously added costimulatory DNA, and which step(s) of the infection cycle RNase 7 interferes with. We quantified viral gene expression by RT-qPCR and flow cytometry, viral genome replication by qPCR, virucidal effects by plaque titration, and plaque formation and the subcellular localization of incoming HSV-1 particles by microscopy. Recombinant RNase 7 restricted HSV-1 gene expression, genome replication, and plaque formation in human keratinocytes. It decreased HSV-1 immediate-early transcripts independently of the induction of interferon-stimulated genes. Its main effect was on intracellular infection processes and not on extracellular virions or virus binding to cells. RNase 7 reduced the amount of cell-associated capsids and the HSV-1 envelope glycoprotein D at 3 but not at 0.5 h postinfection. Our data show that RNase 7 directly restricts HSV-1 infection of human keratinocytes, possibly by promoting the degradation of incoming HSV-1 particles. This suggests that RNase 7 may limit HSV-1 spread in the skin and that mechanisms that reduce its activity in the lesional skin of AD patients may increase their susceptibility to eczema herpeticum.

A Dual Diagnostic Dilemma: Viral Encephalitis and Cerebral Venous Thrombosis.

Herpes encephalitis is caused by herpes simplex virus type 1 (HSV-1) or type 2 (HSV-2). One of the infrequent complications of herpes encephalitis is cerebral venous thrombosis (CVT) because of the inflammation in the brain parenchyma. We report a unique and challenging case of a 14-year-old female patient presenting with confusion, headache, and fever. On examination, there was no neck rigidity and a negative Kernig's sign with no focal neurological deficits. Systemic examination was done to rule out other systems as a cause for her symptoms, and she was empirically treated as a case of encephalitis. An initial computed tomography (CT) scan of the brain without contrast was normal except for a subtle hypoattenuating area involving the right thalamus. Cerebrospinal fluid (CSF) analysis revealed viral infection while we awaited the results of CSF polymerase chain reaction (PCR) and culture analysis for specific microorganisms. Her Glasgow Coma Scale (GCS) deteriorated following an episode of generalized tonic-clonic seizure, and she was subsequently catheterized and an enteral feeding tube (nasogastric tube) was passed. CSF PCR detected HSV-1. Magnetic resonance imaging (MRI) and magnetic resonance venography (MRV) of the brain with contrast revealed encephalitis with superior sagittal sinus, transverse sinus, straight sinus, and vein of Galen thrombosis yielding a diagnosis of HSV encephalitis with concurrent cerebral venous thrombosis. Hence, this required a very specialized and cautious approach to her treatment. She was started on intravenous acyclovir and subcutaneous enoxaparin, and she recovered over the next few days. She did, however, develop acyclovir-induced renal toxicity in the absence of another offending agent, and the dose of the acyclovir was adjusted accordingly. A diagnosis of CVT, although rarely described, should be systematically suspected in patients with HSV encephalitis presenting with sudden deterioration or unexpected neurological findings in the early phase of treatment or inadequate response to treatment for better management and outcomes.

British Association of Sexual Health and HIV UK national guideline for the management of anogenital herpes, 2024.

The guideline provides recommendations on the management of adults with anogenital herpes in the UK. Recommendations include diagnostic tests, management of the primary or first episode of anogenital herpes and recurrences, effectiveness of therapy, prophylaxis, and prevention of transmission between partners, as well as patient centred counselling.

Fulminant Meningitis: A Rare Case of HSV-2 and Cryptococcal Co-Infection in a Patient With AIDS.

Cryptococcal meningitis (CM) is a severe and often fatal infection of the central nervous system that is caused by Cryptococcus spp. Cryptococcal meningitis mainly affects immunocompromised individuals such as those with AIDS, organ transplantation recipients, and those with conditions requiring prolonged immunosuppressive therapy. Infection typically begins with the inhalation of cryptococcal spores, often from bird droppings, which can remain dormant in the lungs and lymph nodes before disseminating to the central nervous system. Signs and symptoms include headache, nausea, and cognitive impairment, which can progress to severe neurological complications if not promptly treated. Even in the era of antifungal and antiretroviral therapies, CM remains a public health challenge with substantial morbidity and mortality. Although rare, sporadic cases of cryptococcal neoformans/gattii coinfection with Mycobacterium tuberculosis, Streptococcus pneumoniae, and Treponema pallidum have been reported in the literature. Herein, we describe an extremely rare case of fulminant meningitis due to herpes simplex virus (HSV)-2 and Cryptococcal neoformans coinfection. Our patient also had cryptococcemia, which is known to increase acute mortality rates in patients with CM.

Efficient Strategy for Synthesizing Vector-Free and Oncolytic Herpes Simplex Type 1 Viruses.

Synthesizing viral genomes plays an important role in fundamental virology research and in the development of vaccines and antiviral drugs. Herpes simplex virus type 1 (HSV-1) is a large DNA virus widely used in oncolytic virotherapy. Although de novo synthesis of the HSV-1 genome has been previously reported, the synthetic procedure is still far from efficient, and the synthesized genome contains a vector sequence that may affect its replication and application. In the present study, we developed an efficient vector-free strategy for synthesis and rescue of synthetic HSV-1. In contrast to the conventional method of transfecting mammalian cells with a completely synthesized genome containing a vector, overlapping HSV-1 fragments synthesized by transformation-associated recombination (TAR) in yeast were linearized and cotransfected into mammalian cells to rescue the synthetic virus. Using this strategy, a synthetic virus, F-Syn, comprising the complete genome of the HSV-1 F strain, was generated. The growth curve and electron microscopy of F-Syn confirmed that its replication dynamics and morphogenesis are similar to those of the parental virus. In addition, by combining TAR with in vitro CRISPR/Cas9 editing, an oncolytic virus, F-Syn-O, with deleted viral genes ICP6, ICP34.5, and ICP47 was generated. The antitumor effect of F-Syn-O was tested in vitro. F-Syn-O established a successful infection and induced dose-dependent cytotoxic effects in various human tumor cell lines. These strategies will facilitate convenient and systemic manipulation of HSV-1 genomes and could be further applied to the design and construction of oncolytic herpesviruses.

Herpes Simplex Virus Esophagitis in a Patient Receiving Long-Term Nasal Corticosteroids: A Rare Case.

Herpetic esophagitis (HE), primarily caused by the herpes simplex virus (HSV)-1, is most commonly encountered in immunocompromised hosts, although it has been occasionally observed in immunocompetent patients. In the immunocompromised setting, it is typically correlated with human immunodeficiency virus (HIV) infection, malignancy, chemotherapy and radiotherapy, solid organ transplant, as well as the use of systemic corticosteroids and other immunosuppressive agents. We present the case of a 35-year-old patient on hemodialysis due to diabetic nephropathy who, after having received intranasal corticosteroids for three weeks, developed nausea, vomiting, and epigastric pain. Gastroscopy and subsequent biopsy revealed ulcerative esophagitis compatible with herpetic infection. Immunohistochemistry was negative for cytomegalovirus (CMV), while subsequent quantitative polymerase chain reaction (PCR) testing was positive for HSV-1, establishing the diagnosis of HSV esophagitis. After a 14-day course of valacyclovir, complete relief of symptoms was achieved. Herpetic esophagitis may occur in immunocompetent persons, whereas intranasal corticosteroids cannot be ruled out as potential contributors. Symptoms such as odynophagia, dysphagia, and fever in that setting warrant further investigation.

Cutaneous perianal herpes simplex virus infection mimicking condylomata acuminata in a renal transplant recipient: A case report and literature review.

Key Clinical Message: Herpes simplex virus (HSV) infection can present atypically in immunosuppressed patients, such as renal transplant recipients, often mimicking conditions like condyloma acuminata. This case report of a 39-year-old male renal transplant recipient underscores the importance of maintaining a high level of clinical suspicion and employing thorough diagnostic techniques, including skin biopsy and polymerase chain reaction, to accurately diagnose chronic lesions and those not responding to initial therapies in these patients. Timely initiation of antiviral therapy, such as intravenous acyclovir, is crucial for improving patient outcomes. Clinicians should be aware of the diverse presentations of HSV in immunocompromised individuals to ensure prompt and effective treatment. Abstract: Herpes simplex virus (HSV) has a worldwide distribution and a wide range of clinical presentations. In immunosuppressed patients, the infection can have atypical presentations. We report a 39-year-old renal transplant recipient male with a cutaneous HSV infection mimicking condyloma acuminata. The diagnosis was confirmed by skin biopsy and polymerase chain reaction. The patient was treated with intravenous acyclovir. This case illustrates the significant clinical challenges in establishing a correct diagnosis of this common infection in these patients. A high level of clinical suspicion will result in a prompt diagnosis and timely initiation of antiviral therapy, which is crucial to better patient outcomes.

Concurrent Varicella-Zoster Virus Reactivation and Recurrent Herpes Simplex Virus Infection in the C2 Dermatome With Varicella-Zoster Virus Encephalitis: A Case Report and Review of the Literature.

Herpes simplex virus (HSV) and varicella-zoster virus (VZV) are common viruses that are present in the general population. However, it is uncommon for both viruses to coincide at the same time and location. These viruses infect the nervous system to establish latency and have been associated with neurological disorders. We discuss a case of co-occurring VZV reactivation and recurrent HSV infection with subsequent VZV encephalitis following an insult to the neurologic system.

A Diagnostically Challenging Case of Recurrent Encephalitis With Impending Herniation.

Encephalitis is characterized by inflammation of the brain parenchyma with typical presenting symptoms of altered mental status and seizures. However, diagnostic workup is complex given the multitude of possible etiologies for encephalitis. Further, recurrence of encephalitis is rare, and understanding its risk factors, mechanisms, prognosis, and optimal treatment remains incomplete. Here, we present the case of a 69-year-old woman admitted to our hospital with altered mental status who was diagnosed with encephalitis based on clinical and imaging findings. This case highlights the diagnostic approaches required to obtain the final diagnosis and the treatment plan that resulted in the patient's eventual return to baseline and functional independence.

Herpes simplex virus 1 inhibits phosphorylation of RNA polymerase II CTD serine-7.

Transcriptional activity of RNA polymerase II (Pol II) is influenced by post-translational modifications of the C-terminal domain (CTD) of the largest Pol II subunit, RPB1. Herpes simplex virus type 1 (HSV-1) usurps the cellular transcriptional machinery during lytic infection to efficiently express viral mRNA and shut down host gene expression. The viral immediate-early protein ICP22 interferes with serine 2 phosphorylation (pS2) by targeting CDK9 and other CDKs, but the full functional implications of this are not well understood. Using Western blotting, we report that HSV-1 also induces a loss of serine 7 phosphorylation (pS7) of the CTD during lytic infection, requiring expression of the two immediate-early proteins ICP22 and ICP27. ICP27 has also been proposed to target RPB1 for degradation, but we show that pS2/S7 loss precedes the drop in total protein levels. Cells with the RPB1 polyubiquitination site mutation K1268R, preventing proteasomal degradation during transcription-coupled DNA repair, displayed loss of pS2/S7 but retained higher overall RPB1 protein levels later in infection, indicating this pathway is not involved in early CTD dysregulation but may mediate bulk protein loss later. Using α-amanitin-resistant CTD mutants, we observed differential requirements for Ser2 and Ser7 for the production of viral proteins, with Ser2 facilitating viral immediate-early genes and Ser7 appearing dispensable. Despite dysregulation of CTD phosphorylation and different requirements for Ser2/7, all CTD modifications tested could be visualized in viral replication compartments with immunofluorescence. These data expand the known means that HSV employs to create pro-viral transcriptional environments at the expense of host responses.IMPORTANCECells rapidly induce changes in the transcription of RNA in response to stress and pathogens. Herpes simplex virus (HSV) disrupts many processes of host mRNA transcription, and it is necessary to separate the actions of viral proteins from cellular responses. Here, we demonstrate that viral proteins inhibit two key phosphorylation patterns on the C-terminal domain (CTD) of cellular RNA polymerase II and that this is separate from the degradation of polymerases later in infection. Furthermore, we show that viral genes do not require the full "CTD code." Together, these data distinguish multiple steps in the remodeling of RNA polymerase during infection and suggest that shared transcriptional phenotypes during stress responses do not revolve around a core disruption of CTD modifications.

Israeli neonatal herpes simplex infection: Unique epidemiology and clinical profile.

To gather national level data on Israeli neonatal HSV (NHSV) infection and to evaluate the distinct clinical characteristics of NHSV and neonatal enteroviral meningitis (NEM). Israeli NHSV patients, hospitalized between January 2015 and April 2022 in 22 medical centers were assessed, together with NEM patients, hospitalized at Sheba Medical Center during the same period. NHSV demographic and clinical characteristics were documented and compared to those of NEM. Eighty-five NHSV (73% males) and 130 NEM (62% males) patients were included. The incidence of NHSV was 5.9/100 000 live births, the common phenotype and HSV type were SEM (53%) and HSV1 (91%), respectively. Horizontal transmission was suspected in 50% cases (of which 67% underwent a Jewish ritual circumcision with direct wound sucking, 33% had relatives with highly suspicious herpetic lesions). Compared with NEM, NHSV tends to present with rash (14% vs. 60%, p-value < 0.01) and seizures (0% vs. 6%, p-value 0.02), while fever, irritability and poor feeding appear more frequently in NEM (94% vs. 18%, p-value < 0.01; 37% vs. 1%, p-value < 0.01; 25% vs. 1%, p-value < 0.01 respectively). Of NEM patients, 28% were treated with acyclovir. Our results mark a decrease in the incidence rate of NHSV in Israel and a prominent mode of horizontal infection acquisition. We underscore the unique localized phenotype of NHSV, in contrast to enterovirus, which tends to cause a systemic disease with constitutional symptoms. These findings should be considered when evaluating the need for comprehensive empirical treatment for HSV in the context of neonatal fever, or according to a certain clinical presentation.

Short-form thymic stromal lymphopoietin (sfTSLP) restricts herpes simplex virus infection of human primary keratinocytes.

Eczema herpeticum (EH) is a disseminated severe herpes simplex virus type 1 (HSV-1) infection that mainly occurs in a subset of patients suffering from atopic dermatitis (AD). EH is complex and multifaceted, involving immunological changes, environmental influences, and genetic aberrations. Certain genetic variants of the thymic stromal lymphopoietin (TSLP) may predispose to develop severe HSV-1-induced eczema. Therefore, we investigated the impact of TSLP on HSV-1 infection. TSLP encodes for two distinct forms: a long-form (lfTSLP), primarily associated with type 2 immunity, and a short-form (sfTSLP) with anti-inflammatory and antimicrobial properties. While sfTSLP reduced HSV-1 infectibility in human primary keratinocytes (HPK), lfTSLP did not. In HPK treated with sfTSLP, HSV-1 gene expression, and replication decreased, while virion binding to cells and targeting of incoming capsids to the nucleus were not diminished compared to untreated cells. sfTSLP caused only minor changes in the expression of innate immunity cytokines, and its inhibition of HSV-1 infection did not require de novo protein synthesis. Time window experiments indicated a different antiviral mechanism than LL-37. sfTSLP showed the strongest antiviral effect when administered to HPK before or after inoculation with HSV-1, and outperformed the inhibitory potential of LL-37 under these conditions. Our data show that sfTSLP has antiviral functions and promotes repression of the HSV-1 infection in HPK.

A sheep in wolf's clothing? Herpes-simplex-virus endobronchial pseudotumor.

Central airway obstruction (CAO) is generally defined as airflow limitation due to >50 % occlusion and is most commonly due to malignant etiologies. However, benign etiologies, including herpes-simplex-virus (HSV) endobronchial pseudotumor, can occur. Due to the rarity of HSV causing airway obstruction, an evidence-based approach to the bronchoscopic resection and standardization of therapy after removal are lacking. Herein, we present a case of HSV pseudotumor successfully managed by argon-plasma-coagulation (APC) debulking via bronchoscopy and medical management with intravenous foscarnet due to failed treatment with acyclovir for previous HSV lesions.