Herpes Labialis Research Articles

The Influence of Wind Musical Instruments on the Orofacial System.

The main objective of this study was to assess whether there are differences in the muscular and occlusal levels between wind players and the general population, in addition to assessing the different repercussions depending on the embouchure type. Two cohorts were chosen: one of them comprised intermediate students related to the practice of a wind instrument (n = 39), and the other one, harmonized with the former, comprised secondary students that served as a control group (n = 19). Overjet, overbite, presence of lip abrasion and/or erosion, Angle's molar class, Little's irregularity index, dental abrasion, presence of labial herpes, presence of tooth sensitivity, and presence of articular noises muscle pain were evaluated. Significant statistical differences between the groups were found regarding overjet, overcrowding of teeth, lower lip erosion, and dental abrasion, which was higher in musicians. Lastly, within the group of musicians, it was proven that tooth sensitivity was higher in the group of brass musicians. Wind instrument practice may be a risk factor for developing some orofacial involvement, and there are no differences among the various existing mouthpieces.

Recent Advances in the Study of Alphaherpesvirus Latency and Reactivation: Novel Guidance for the Design of Herpesvirus Live Vector Vaccines.

Alphaherpesviruses, including herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), and varicella-zoster virus (VZV), infect a diverse array of hosts, spanning both humans and animals. Alphaherpesviruses have developed a well-adapted relationship with their hosts through long-term evolution. Some alphaherpesviruses exhibit a typical neurotropic characteristic, which has garnered widespread attention and in-depth research. Virus latency involves the retention of viral genomes without producing infectious viruses. However, under stress, this can be reversed, resulting in lytic infection. Such reactivation events can lead to recurrent infections, manifesting as diseases like herpes labialis, genital herpes, and herpes zoster. Reactivation is a complex process influenced by both viral and host factors, and identifying how latency and reactivation work is vital to developing new antiviral therapies. Recent research highlights a complex interaction among the virus, neurons, and the immune system in regulating alphaherpesvirus latency and reactivation. Neurotropic alphaherpesviruses can breach host barriers to infect neurons, proliferate extensively within their cell bodies, and establish latent infections or spread further. Whether infecting neurons or spreading further, the virus undergoes transmission along axons or dendrites, making this process an indispensable part of the viral life cycle and a critical factor influencing the virus's invasion of the nervous system. Research on the transmission process of neurotropic alphaherpesviruses within neurons can not only deepen our understanding of the virus but can also facilitate the targeted development of corresponding vaccines. This review concentrates on the relationship between the transmission, latency, and activation of alphaherpesviruses within neurons, summarizes recent advancements in the field, and discusses how these findings can inform the design of live virus vaccines for alphaherpesviruses.

Minor Ailments and Pharmacist Management in Ontario, Canada: Attachment and Primary Care

Minor ailments (MA) are health conditions that can be managed with minimal prescribed treatment and/or self-care strategies. In Ontario, Canada, pharmacists were given authority to deliver service for thirteen MAs on January 1, 2023, with an additional six MAs on October 1, 2023. This study aims to identify patterns of MA service provision and describe characteristics of recipients of MA services. A cross-sectional analysis of linked health administrative data, including pharmacist billing for MA services, patient demographics, and physician and hospital billing data, was conducted. Delivery of MA services prescribed in Ontario from January 1 to December 31, 2023 were analyzed with key demographics (age, sex, income, new arrival status, comorbidity), health care utilization (ED, hospitalization) and primary care attachment. In 2023, 547,673 (3.6%) Ontario residents received at least one MA service, with the top 5 services being urinary tract infections (199,282), conjunctivitis (153,021), herpes labialis (46,659), allergic rhinitis (41,521), and dermatitis (39,365). Compared to all Ontario residents, the MA service recipients were more likely to be people with a higher rate of ED visits (41.7% vs. 32.4%), comorbidities (17.5% vs. 9.7%), higher incomes (highest income quintile, 23.1% vs. 20.1%; lowest income quintile, 16.5% vs. 19.4%), and hospitalizations (23.6% vs. 17.6%), and less likely to be newcomers to Ontario (8.7% vs. 13.1%). They were more likely to be attached to a primary care provider (91.3% vs. 84.7%). This study provides insight into early users of this program, and sheds light on those with systemic vulnerabilities and equity deserving groups.

Predictive Factors for Herpes Simplex Virus Reactivation in Patients with Trigeminal Neuralgia After Surgery

This study aimed to investigate the predictive factors associated with the reactivation of herpes simplex virus (HSV) in patients with trigeminal neuralgia (TN) after surgery, and to determine whether there is a correlation between reactivation and surgical efficacy. This study included 190 patients who underwent surgery between January 2020 and December 2021. Postoperative HSV reactivation was defined as the presence of perioral or gingival herpes and herpes labialis within 1 week postoperatively. Logistic regression analysis was used to evaluate clinical characteristics as potential predictors of HSV reactivation. Additionally, Spearman's rank correlation coefficient was used to determine any correlation between the postoperative barrow neurological institute (BNI) pain intensity score and HSV reactivation. Of the 190 patients, 56 (29.5%) experienced postoperative HSV reactivation. Both univariate and multivariate analyses identified several significant predictors of HSV reactivation, such as a history of HSV infection, previous trigeminal nerve-damaging surgery, the use of internal neurolysis (IN) as a surgical technique, and an operation time of ≥25 min. No significant correlation was found between HSV reactivation and pain relief, as measured by BNI scores. HSV reactivation was observed in a considerable proportion of patients with TN. Long operative times (≥25 min), the use of IN as a surgical technique, a history of HSV infection, and previous trigeminal nerve-damaging surgery were identified as risk factors. Further research is needed to optimize surgical procedures and develop targeted management protocols to reduce the risk of HSV reactivation.

Israeli neonatal herpes simplex infection: Unique epidemiology and clinical profile

AbstractTo 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.

Getting insights into chemical composition and antiherpetic capability of jujube (Ziziphus jujuba mill.) drupes

Food plant diversity in bioactive compounds makes them an exploitable resource in the search for effective natural products to prevent or treat viral infections. Therefore, in the framework aimed at studying the antiviral properties of extractive mixtures from fruits (and their waste) grown in the Campania Region (Italy), jujube drupes (Zizyphus jujuba Mill.) were our focus. The drupes were dissected into their peel, pulp and seed parts, each of which was extracted by ultrasound-assisted maceration and further fractionated, thus obtaining, beyond the sugar fraction, a polyphenolic fraction and a lipid fraction. UHPLC-HR MS/MS tools highlighted that the polyphenolic component of the seed was strongly dissimilar from that of the edible parts, being constituted by swertisin and its derivatives. Moreover, the peel mostly accounted for triglycosylated flavonols, whereas the pulp was rich in volatile aromatic glycosides. Among lipids, p-coumaroyl triterpenes mainly characterized the peel. All fractions were screened for their cytotoxicity, and non-toxic concentrations of each extract were tested against herpes simplex virus type 1 (HSV-1) by plaque assays. Molecular tests and Western blot analyses were also carried out. The jujube mixtures, in detail the peel and pulp polyphenolic fractions, and peel lipophilic fraction (the latter enriched mainly in ursane-type triterpenes), showed a marked inhibitory activity against HSV-1 acting in the early stages of viral infection and preventing attachment of the virus to the host cell. The acquired data suggest jujube active mixtures as promising candidates for the prevention and treatment of herpetic lesions.

Bioadhesive gel containing 5 % acyclovir for the treatment of herpes labialis: Preclinical development

Acyclovir is widely indicated for the treatment of herpes labialis, an infection typically caused by herpes simplex virus 1 (HSV-1). The standard treatment is based on the use of this antiviral in conventional topical semi-solid formulations (ointments, creams or gels), which have limitations such as low skin adherence and poor patient compliance. On the other hand, therapeutic bioadhesive gels (TBG) are semi-solid formulations that form a thin and transparent polymeric film in situ, displaying superior cosmetic attributes than conventional semi-solid forms and offering improved skin maintenance and patient compliance. In this study, a TBG containing 5 % of acyclovir was developed and characterized in terms of assay, impurities, appearance, pH, viscosity, particle size and morphology and microbiology count, complying with specifications. Stability studies showed that acyclovir-TBG was stable for at least 3 years under the experimental conditions carried out according to the International Council for Harmonisation (ICH) guidelines. Moreover, its cosmetic attractiveness and film-forming ability were considered positive and the in vitro penetration studies revealed a 23.8-fold increase in acyclovir retained percentage in the skin compared to the reference product Zovirax® (11.9 vs 0.5 % after 24 h, respectively). Finally, in vivo skin and ocular irritation studies as well as dermal tolerance studies did not show any negative sign in the macroscopic and microscopic examination. Thus, the proposed formulation could be a good and safe alternative for the topical treatment of lesions caused by HSV-1.

Genetic susceptibility association between viral infection and colorectal cancer risk: a two-sample Mendelian randomization analysis

BackgroundThe genetic susceptibility association between viral infection and the risk of colorectal cancer (CRC) has not been established.MethodsWe conducted two-sample Mendelian randomization (MR) analysis using genome-wide association study (GWAS) data. In addition to traditional MR methods, we employed several other approaches, including cML, ConMix, MR-RAPS, and dIVW, to comprehensively assess causal effects. Sensitivity analyses were also performed to ensure the robustness of the results.ResultsAfter sensitivity analysis, presence of SNPs linked to increased susceptibility to cold sores infection was found to decrease the risk of CRC (OR: 0.73, 95% CI: 0.57–0.93, P = 0.01). In subgroup analysis, presence of SNPs linked to increased susceptibility to viral hepatitis (OR: 0.89, 95% CI: 0.81–0.98, P = 0.02) and infectious mononucleosis (OR: 0.91, 95% CI: 0.84–0.98, P = 0.02) were associated with a decreased risk of colon cancer, while measles virus (OR: 1.41, 95% CI: 1.07–1.85, P = 0.01) was associated with an increased risk of colon cancer. Presence of SNPs linked to increased susceptibility to herpes zoster (OR: 1.26, 95% CI: 1.05–1.52, P = 0.01) was associated with an increased risk of rectal cancer, while infectious mononucleosis (OR: 0.809, 95% CI: 0.80–0.98, P = 0.02) was associated with a decreased risk.ConclusionThe study provides the first evidence of the genetic susceptibility associations between different viral infections and CRC, enhancing our understanding of the etiology of CRC.

Use of mixed saliva in the diagnosis of recurrent herpetic stomatitis in patients with dental problems: An interventional single-center, prospective, randomized, uncontrolled study

BACKGROUND: Recurrent herpetic stomatitis, also known as oral herpes, is one of the most common viral diseases of the oral cavity. Currently, saliva is widely used in innovative diagnostic methods. However, there are only limited data supporting the diagnostic value of salivary biomarkers in herpes infections. AIM: To establish the informative value of using the wedge-shaped dehydration method and the express method for determining salivary amylase activity in patients with recurrent herpetic stomatitis. MATERIALS AND METHODS: Diagnosis of recurrent herpes stomatitis was carried out based on the results of a clinical examination and confirmed using molecular genetic (PCR with real-time detection) and serological studies (ELISA — VectoHSV-IgG test system). For non-invasive diagnosis of recurrent herpetic stomatitis, we used crystallography methods — wedge-shaped dehydration of oral fluid and an express method for determining salivary amylase activity. The study included 26 patients with HHS in the acute stage (frequency of exacerbations of 4 or more per year) and 14 patients in the control group with no history of episodes of herpetic stomatitis. RESULTS: The results of crystallography of mixed saliva and determination of salivary amylase activity in patients diagnosed with recurrent herpes before and after treatment are presented. Specific changes in facies in the protein zone were established during wedge-shaped dehydration during the exacerbation period and an increase in salivary amylase activity in patients with recurrent herpetic stomatitis in the acute stage. CONCLUSION: To confirm the diagnosis of recurrent herpetic stomatitis at a dental appointment, a non-invasive method of wedge-shaped dehydration using samples of mixed saliva is recommended, and to determine the effectiveness of treatment, along with clinical indicators, the most informative is a rapid test based on a study of the level of amylase in mixed saliva.

Trilayered nanocellulose-based patches loaded with acyclovir and hyaluronic acid for the treatment of herpetic lesions

This study focuses on the preparation of layered bacterial nanocellulose (BNC) patches for drug delivery and wound healing in the context of herpes labialis. Nanostructured patches were prepared by selective aqueous diffusion of acyclovir (ACV, antiviral drug), hyaluronic acid (HA, skin healing promoter), and glycerol (GLY, plasticizer and humectant) in the BNC network, followed by assembly into trilayered patches with ACV on the central layer of the patch (ACVT) or divided between two layers (ACVH), to modulate drug release. Both patches showed good layers' adhesion and thermal stability (125 °C), UV barrier properties, good static (Young's modulus up to 0.9 GPa (dry) and 0.7 GPa (wet)) and dynamic mechanical performance, and adhesion strength (21 kPa) comparable to or higher than other materials and commercial adhesives for wound healing. In vitro drug dissolution showed faster ACV release from the ACVH patch (77 ± 5 %, 10 min) than from the ACVT one (50 ± 7 %), suggesting efficient drug delivery. ACVH closely resembled a commercial cream formulation in terms of release and permeation profiles. The patches were non-cytotoxic toward L929 fibroblasts, promoting cell adhesion and wound closure (in vitro). These results underscore the dual-action potential of the layered patches for managing herpetic lesions.

Pritelivir for the treatment of nucleoside analogue–resistant orolabial herpes simplex virus 2 in a person living with HIV

Background: Nucleoside analogue–resistant herpes simplex virus infections are increasingly observed especially in immunocompromised patients. Currently, other options for treatment such as foscarnet and cidofovir are limited by difficulty of administration and significant risk of toxicity. Our report describes use of pritelivir, a novel helicase-primase inhibitor, in the treatment of nucleoside analogue–refractory orolabial HSV-2 infection. Methods: In 2017, a 53-year-old male with HIV on therapy presented with swelling of the right upper lip and a solid lesion inferior to the right nostril. Biopsy revealed cytopathic effects and immunohistochemistry staining confirming herpes simplex virus infection. The patient received multiple treatment courses including nucleoside analogue therapy, topical and intravenous foscarnet and cidofovir, and topical imiquimod but these failed to establish a significant and durable therapeutic response. Results: A swab of the lesion tested positive for HSV-2 via PCR. Subsequent genotyping revealed a M183X mutation in UL23 expected to convey resistance to acyclovir and penciclovir. The patient was started on oral pritelivir 400 mg once followed by 100 mg daily for 27 days, obtained through Health Canada's Special Access Program, resulting in near complete resolution of the lesion. Conclusion: Pritelivir is a novel helicase-primase inhibitor that appears to be an attractive option for management of resistant herpes simplex infections due to its unique mechanism, excellent oral bioavailability, and minimal toxicity. To our knowledge, this is the first described case of treatment of nucleoside analogue–resistant orolabial herpes simplex 2 infection with pritelivir and the first documented use of pritelivir in Canada.

Evaluation of oral herpes simplex virus shedding among solid organ transplant recipients: A pilot study.

Herpes simplex viruses (HSVs) frequently reactivate during immunosuppression and may be a risk factor for adverse outcomes after solid organ transplant (SOT). While suppressive antiviral therapy reduces the risk of symptomatic HSV reactivation, the kinetics of asymptomatic viral shedding with chronic immunosuppression after transplant are not well understood. We report the characteristics of oral HSV shedding among 15 HSV-1 seropositive SOT recipients (n = 8 liver, n = 7 kidney, median age 58.5 years, median 20 months post-transplant) who were not taking daily antiviral suppressive therapy. Participants self-collected oral swabs three times daily for 6 weeks for HSV quantification and recorded the presence of oral symptoms or lesions in a diary. Sample collection adherence was high (median 122 swabs/person, range: 85.7%-101.6% of expected swabs). Most participants (n = 12, 80%) experienced at least one shedding episode, with a median shedding rate of 8.9% (range: 0%-33.6%). There were 32 total shedding episodes, 24 (75%) of which occurred without symptoms or lesions. For episodes of known duration, the median length was 21.8 hrs (interquartile range: 10.8-46.1 hrs). Most shedding episodes (78.1%) lasted >12 hrs, suggesting that twice-daily sampling may be sufficient to detect most episodes. These data show that self-collection of oral swabs is feasible for patients who have undergone SOTs and can provide insight into the frequency of oral HSV reactivation, which can be used to design future studies in this population.

Efficacy of adjuvant photobiomodulation therapy in recurrent herpes labialis, a randomized clinical trial study

ObjectiveThis 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 MethodsIn 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. ResultsPain 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). ConclusionPBMT can be used as an adjuvant tool to acyclovir cream, due to higher potential in reducing postoperative pain, lesion size and also patients satisfaction.

Dupilumab in Adults With Moderate to Severe Atopic Dermatitis

Moderate to severe atopic dermatitis (AD) is a chronic inflammatory skin disease that often requires continuous long-term systemic management. Long-term safety and efficacy data for treatment options are critically important. To assess the safety and efficacy of dupilumab treatment for up to 5 years in adults with moderate to severe AD. The 5-year LIBERTY AD open-label extension study was conducted from September 2013 to June 2022 at 550 sites in 28 countries. The study enrolled adult patients with moderate to severe AD who had participated in previous dupilumab clinical trials. Data were analyzed from August 2022 to February 2023. At enrollment, patients initiated a regimen of subcutaneous dupilumab, 200 mg, weekly (400-mg loading dose). The regimen was amended in June 2014 to dupilumab, 300 mg, weekly (600-mg loading dose) based on a dose-ranging study and again in November 2019 to dupilumab, 300 mg, every 2 weeks to align with the regulatory regimen approvals. The primary end points were the incidence and rate of treatment-emergent adverse events (TEAEs). Key secondary end points included incidence and rate of serious TEAEs and adverse events of special interest, proportion of patients achieving an Investigator's Global Assessment (IGA) score of 0 or 1 (clear or almost clear), and proportion of patients with 75% or more improvement in the Eczema Area and Severity Index (EASI) from the parent study baseline. A total of 2677 patients were enrolled and treated in the open-label extension study; 1611 (60.2%) were male, and the mean (SD) age was 39.2 (13.4) years. A total of 334 patients (12.5%) completed treatment up to week 260. The most common reasons for withdrawal were due to regulatory approval of dupilumab in compliance with the study protocol (810 of 1380 [58.7%]), patient withdrawal (248 of 1380 [18.0%]), and adverse events (116 of 1380 [8.4%]). Exposure-adjusted rates of TEAEs were generally stable or declined throughout the study. Common TEAEs (incidence of 5% or greater) included nasopharyngitis, worsening AD, upper respiratory tract infection, conjunctivitis, conjunctivitis allergic, headache, oral herpes, and injection-site reaction. At week 260, 220 of 326 patients (67.5%) achieved an IGA score of 0 or 1 and 288 of 324 (88.9%) achieved 75% or greater improvement in the EASI. The mean (SD) EASI score was 16.39 (14.60) at baseline and 2.75 (5.62) at end of study. In this study, there was sustained safety and efficacy of continuous long-term dupilumab treatment for adults with moderate to severe AD.

From a focal skin issue to a systemic disease: the multifaceted nature of cold sores, novel findings.

Cold sores, a viral infection caused by the herpes simplex virus, are a prevalent affliction affecting millions of people across the globe. In this article, we explore the constitutional symptoms of cold sores in more detail to reveal what patients experience during an outbreak. A total of 400 participants with cold sores were enrolled in our cross-sectional study. Participants were interviewed using a structured questionnaire that collected information on demographic characteristics, clinical symptoms, and constitutional symptoms associated with cold sores such as fever, headache, muscle aches, swollen lymph nodes, malaise, and nervousness. Participants were asked to rate the severity of each symptom on a scale of 1-10. The commonly reported constitutional symptom was malaise (51.4%), and fever (48.8%), followed by headache (39.3%), muscle aches (33.8%), swollen lymph nodes (28.3%), and nervousness (32.2%). Nervousness was reported by 91 patients (22%) on the first day, which was followed by the appearance of a cold sore later. The median severity score for fever was 5.0 (IQR = 3.0), for headache was 5.0 (interquartile ranges = 4.0), for muscle aches was 4.0 (interquartile ranges = 3.0), and for swollen lymph nodes was 4.0 (interquartile ranges = 2.0). Our study provides important insights into the prevalence and impact of constitutional symptoms in individuals with cold sores. Our findings demonstrate that constitutional symptoms such as fever, headache, malaise, and nervousness are common in individuals with cold sores, with a prevalence of up to 51.4% in our study.

Comparison of strain specific pathogenicity of Herpes Simplex Virus Type 1 by high-throughput sequencing

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.

Asymptomatic herpes simplex virus brain infection elicits cellular senescence phenotypes in the central nervous system of mice suffering multiple sclerosis-like disease

Experimental autoimmune encephalomyelitis (EAE) is a demyelinating disease affecting the central nervous system (CNS) in animals that parallels several clinical and molecular traits of multiple sclerosis in humans. Herpes simplex virus type 1 (HSV-1) infection mainly causes cold sores and eye diseases, yet eventually, it can also reach the CNS, leading to acute encephalitis. Notably, a significant proportion of healthy individuals are likely to have asymptomatic HSV-1 brain infection with chronic brain inflammation due to persistent latent infection in neurons. Because cellular senescence is suggested as a potential factor contributing to the development of various neurodegenerative disorders, including multiple sclerosis, and viral infections may induce a premature senescence state in the CNS, potentially increasing susceptibility to such disorders, here we examine the presence of senescence-related markers in the brains and spinal cords of mice with asymptomatic HSV-1 brain infection, EAE, and both conditions. Across all scenarios, we find a significant increases of senescence biomarkers in the CNS with some differences depending on the analyzed group. Notably, some senescence biomarkers are exclusively observed in mice with the combined conditions. These results indicate that asymptomatic HSV-1 brain infection and EAE associate with a significant expression of senescence biomarkers in the CNS.

Leveraging biotin-based proximity labeling to identify cellular factors governing early alphaherpesvirus infection.

Neurotropic alphaherpesviruses, including herpes simplex virus type 1 and pseudorabies virus, establish a lifelong presence within the peripheral nervous system of their mammalian hosts. Upon entering cells, two conserved tegument proteins, pUL36 and pUL37, traffic DNA-containing capsids to nuclei. These proteins support long-distance retrograde axonal transport and invasion of the nervous system in vivo. To better understand how pUL36 and pUL37 function, recombinant viral particles carrying BioID2 fused to these proteins were produced to biotinylate cellular proteins in their proximity (<10 nm) during infection. Eighty-six high-confidence host proteins were identified by mass spectrometry and subsequently targeted by CRISPR-Cas9 gene editing to assess their contributions to early infection. Proteins were identified that both supported and antagonized infection in immortalized human epithelial cells. The latter included zyxin, a protein that localizes to focal adhesions and regulates actin cytoskeletal dynamics. Zyxin knockout cells were hyper-permissive to infection and could be rescued with even modest expression of GFP-zyxin. These results provide a resource for studies of the virus-cell interface and identify zyxin as a novel deterrent to alphaherpesvirus infection.IMPORTANCENeuroinvasive alphaherpesviruses are highly prevalent with many members found across mammals [e.g., herpes simplex virus type 1 (HSV-1) in humans and pseudorabies virus in pigs]. HSV-1 causes a range of clinical manifestations from cold sores to blindness and encephalitis. There are no vaccines or curative therapies available for HSV-1. A fundamental feature of these viruses is their establishment of lifelong infection of the nervous system in their respective hosts. This outcome is possible due to a potent neuroinvasive property that is coordinated by two proteins: pUL36 and pUL37. In this study, we explore the cellular protein network in proximity to pUL36 and pUL37 during infection and examine the impact of knocking down the expression of these proteins upon infection.

Pathophysiology of oral lesions subsequent to SARS-CoV-2 vaccination: A systematic review

Abstract Amidst worldwide reports of adverse oral lesions subsequent to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, the current systematic review planned to determine the prevalence of adverse oral events in adult individuals (≥18 years) after SARS-CoV-2 vaccination, emphasizing upon the type and dose of vaccine, time of onset, and underlying pathophysiology. The registered protocol (PROSPERO CRD42023421307), conforming with PRISMA guidelines, included an all-inclusive literature search through online databases, consisting of Scopus, PubMed/MEDLINE, Web of Science, Lilacs, Livivo, and PROSPERO, completed on 2 May 2023, followed by assessment of risk of bias by Joana Briggs Institute Evaluation Checklist. Due to the paucity of literature, case reports and case series were included. Self-reported lesions were excluded. Qualitative synthesis employing Microsoft Excel software 2019 revealed low prevalence (43 subjects) from 26 case reports and two case series. There were multiple erosive oral ulcers on gingiva, palate, burning pain in the mouth, xerostomia, tongue fissuring and glossitis, palatal petechiae, diffuse erythematous lesions and loss of smell (16.2%), primary herpetic gingivostomatitis (21%), oral lichen planus (16.2%), Stevens-Johnson syndrome (6.9%), Bell’s palsy in four cases where two cases were Guillain-Barré syndrome (9.3%), erythema multiforme (11.6%), pemphigus (4.6%), idiopathic thrombocytopenic purpura (6.9%), unilateral hypoglossal nerve palsy (4.6%), and trigeminal neuralgia (2.3%). Maximum cases (22 subjects) presented oral lesions after Pfizer (BNT162b2) SARS-CoV-2 vaccine. No association was found between the vaccine type and dose with oral side effects. Dentists must be aware of the oral adverse effects after coronavirus disease 2019 vaccination to better understand the pathogenesis and the risk factors associated with such reactions.

A rare case of Good’s syndrome presented with recurrent COVID pneumonia

A 45-year-old male patient with a history of thymectomy presented to the emergency with a history of cough, breathlessness, and fever for the past 3 days. He had undergone a thymectomy in the year 2017 for a thymoma. He had no symptoms consistent with myasthenia gravis. He had a history of COVID pneumonia in November 2021 and another episode in July 2022, following which he made a full recovery. The patient also gave a history of recurrent infections of oral candidiasis and herpes labialis, which responded to antifungal and antiviral medications. Considering his history of thymectomy and recurrent infections, his immunoglobulin levels were measured and came out to be low. A diagnosis of Good’s syndrome was made with a very rare presentation with recurrent COVID pneumonia.