Herpes Simplex Virus Type Research Articles

Twenty years of herpes simplex virus type 2 (HSV-2) research in low-income and middle-income countries: systematic evaluation of progress made in addressing WHO prioritiesfor research in HSV-2 epidemiology and diagnostics

IntroductionLow-income and middle-income countries (LMICs) have a high burden of herpes simplex virus type 2 (HSV-2) infection, which has been strongly associated with HIV. In 2001, the WHO hosted a...

Combined Effect of Basic Antiherpetic Drugs with a New Inhibitor of the Terminase Complex of Herpes Simplex Virus Type 1 in Vero Cell Cultures.

Carriers of herpes simplex virus type 1 (HSV-1) account for more than 90% of the global population. Infection manifests itself in the formation of blisters and ulcers on the face or genitals and can cause blindness, encephalitis, and generalized infection. All first- and second-line modern antiherpetic drugs selectively inhibit viral DNA polymerase. The purine-benzoxazine conjugate LAS-131 ((S)-4-[6-(purin-6-yl)aminohexanoyl]-7,8-difluoro-3,4-dihydro-3-methyl-2H-[1,4]benzoxazine), which we have described earlier, uses the large subunit of the HSV-1 terminase complex as a biotarget and selectively inhibits HSV-1 reproduction in vitro. Basically new results were for the first time obtained to characterize the combined effect on human herpesvirus infection for LAS-131 used in combination with practically significant antiviral compounds, including the nucleoside analogs acyclovir (ACV), penciclovir (PCV), ganciclovir (GCV), brivudine (BVdU), iododeoxyuridine (IdU), and adenine arabinoside (Ara-A); the nucleoside phosphonate analog cidofovir (CDV); and the pyrophosphate analog foscarnet (FOS). A cytopathic effect (CPE) inhibition assay showed that the drug concentration that inhibited the virus-induced CPE by 50% decreased by a factor of 2 (an additive effect, FOS) or more (a synergistic effect; ACV, PCV, GCV, IdU, BVdU, Ara-A, and CDV) when the drugs were used in combination with LAS-131. Nonpermissive conditions for HSV-1 reproduction were thus created at lower drug concentrations, opening up new real possibilities to control human herpesvirus infection.

Chemical Composition, Antifungal, Antibacterial, Antioxidant, Antiviral and Cytotoxic Activities of Ruta chalepensis L. Fixed Oil from Saudi Arabia

An aromatic plant is called Ruta chalepensis L. known locally as “Fidjel,” grows in rocky, arid places. Its pharmacological activities are pleiotropic. The goal of the present investigation was to use GCMS and HPLC analysis to identify the chemical constituents of oil extracted from Ruta chalepensis L. and assess its antibacterial, antifungal, antioxidant, antiviral, and anticancer properties. Linoleic acid was the most predominant acid found in Ruta chalepensis L. oil, then oleic acid, palmitic acid, and linolenic acid. 13.64 μg/mL of tocopherol (α-, β-, and γ-tocopherol) was identified. The primary phytosterols are β-sitosterol and campesterol. At 200 μL/mL of Ruta chalepensis L. oil, phenolic components rated 84.4 GAE/mL and had 94.0% antioxidant activity. Zone inhibition efficacy of Ruta chalepensis L. oil against microbial strains, particularly E. coli with a diameter of 42.3 mm, was demonstrated. MBC (30 μL/mL and 40 μL/mL) are the bactericidal action against E. coli and S. aureus, while MIC bacteriostatic (30 μL/mL) was also demonstrated. However, Ruta chalepensis L. oil was ineffective against Saccharomyces cervisia and fungal strains. Weak inhibitory impact of Ruta chalepensis L. oil was observed against the PC-3 (prostate cancer) cell line. Nonetheless, it had a significant inhibitory impact on the A2780 (ovarian cancer) cell line. At 100 μg/mL of oil, Ruta chalepensis L. oil showed a low antiviral impact (7.93±2.03%) against the herpes simplex virus type 2 (HSV-2). Oil from Ruta chalepensis L. is a promising option for the medical management of non- transmissible illnesses, since it is wealthy in antioxidants and bioactive substances.

Zebrafish as a model organism for virus disease research: Current status and future directions

Zebrafish (Danio rerio) have emerged as valuable models for investigating viral infections, providing insights into viral pathogenesis, host responses, and potential therapeutic interventions. This review offers a comprehensive synthesis of research on viral infections using zebrafish models, focusing on the molecular mechanisms of viral action and host-virus interactions. Zebrafish models have been instrumental in elucidating the replication dynamics, tissue tropism, and immune evasion strategies of various viruses, including Chikungunya virus, Dengue virus, Herpes Simplex Virus type 1, and Influenza A virus. Additionally, studies utilizing zebrafish have evaluated the efficacy of antiviral compounds and natural agents against emerging viruses such as SARS-CoV-2, Zika virus, and Dengue virus. The optical transparency and genetic tractability of zebrafish embryos enable real-time visualization of viral infections, facilitating the study of viral spread and immune responses. Despite challenges such as temperature compatibility and differences in host receptors, zebrafish models offer unique advantages, including cost-effectiveness, high-throughput screening capabilities, and conservation of key immune pathways. Importantly, zebrafish models complement existing animal models, providing a platform for rapid evaluation of potential therapeutics and a deeper understanding of viral pathogenesis. This review underscores the significance of zebrafish research in advancing our understanding of viral diseases and highlights future research directions to combat infectious diseases effectively.

Herpes Simplex Virus Type 1 Infection Up-regulates miR-221-5P in Oral Squamous Cell Carcinoma

Background: Herpes simplex virus type 1 (HSV-1) infection contributes to oral carcinoma, but its carcinogenic role has not been elucidated yet. MicroRNAs (miRNAs) are involved in carcinogenesis. The aim of the present study was to examine the effect of HSV-1 infection on the expression of miR-29c, miR-221-5P, miR-21-5P, and miR-96-5P in patients with oral squamous cell carcinoma (OSSC). Methods: Twenty-five cases of OSCC and 25 samples of normal oral mucosa were examined in this study. The SYBR real-time polymerase chain reaction (RT-PCR) was completed to confirm the presence of HSV-1. The expressions of miR-29c, miR-221-5P, miR-21-5P, and miR-96-5P were measured using RT-PCR. Results: The expression of miR-221-5P was significantly higher in OSCC with HSV-1 infection compared to non-infected cases (P=0.007). The expressions of miR-29c, miR-21-5P, and miR-96-5P were not significantly different between OSCCs with HSV-1 infection and controls (P=0.27, P=0.66, and P=0.23, respectively). Conclusion: HSV-1 infection had an up-regulation effect on miR-221-5P in OSCC. This finding proposes a novel mechanism for HSV-1 infection in the development of OSCC.

Перинатальні особливості при рецидивній герпесвірусній інфекції

The aim of the study is to determine perinatal features in recurrent herpesvirus infection (HVI). Materials and methods. 160 pregnant women and their newborns were examined: 100 women with recurrence during pregnancy of herpes simplex virus type 1 and/or 2 (HSV-1 and/or HSV-2), 30 women seropositive for HSV-1 and/or HSV-2 without relapse during pregnancy, 30 women seronegative for HVI. Peculiarities of the perinatal period and the development of children at 1 year of life were studied. The obtained data were processed by the methods of variational statistics, using the Student's t-test and Fisher's angular transformation. The Microsoft Excel statistical analysis package was used. Results. Recurrent HVI during pregnancy is associated with a significantly increased frequency of pregnancy complications (threat of abortion in 52.0% of women, threat of premature birth in 21.0%, anemia of pregnancy in 54.0%, placental insufficiency in 72.0%, fetal distress in 24.0%), childbirth (abnormalities of labor in 28.0%, fetal distress in 15.0%), postpartum blood loss (5.0%). Children are more often born prematurely (6.0%), in a state of asphyxia (24.0%), with reduced body weight (28.0%). In the structure of complications of the neonatal period, infections typical for the perinatal period, damage to the nervous system, respiratory distress syndrome prevail. In the period of life up to 1 year, a quarter of children belong to the group of frequently and long-term patients, 14.0% are underweight, and a third are overweight. One third had anemia, 14.0% had exudative diathesis, 24.0% had a syndrome of movement disorders and increased neuro-reflex excitability. Delayed motor development in combination with delayed reduction of muscle tone, delayed language development, game skills, and communication skills were noted. Conclusions. Recurrent HVI during pregnancy causes a high frequency of perinatal disorders, which requires preconception counseling and pregnancy management in order to avoid recurrences of GVI, prevent stressful situations, join infections, and correct the psycho-emotional state. The study was carried out in accordance with the main provisions of GCP ICH and the Declaration of Helsinki, agreed with the Local Ethics Committee of the institution. All studies were performed after obtaining the informed consent of the women. The authors declare no conflict of interest.

CRISPR/Cas9-mediated genome editing of the thymidine kinase gene in a clinical HSV-1 isolate identifies F289S as novel acyclovir-resistant mutation

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

Small Animal Models to Study Herpes Simplex Virus Infections.

Herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) are two of the most prevalent human viruses worldwide. They are known to cause a variety of diseases including genital herpes, meningitis, encephalitis, cold sores and herpes stromal keratitis. The seropositive rate for HSV-1 is around 90%, whereas for HSV-2 it remains around 20-25% for the general adult population. The infections caused by these viruses remain difficult to study because a large proportion of infected individuals are asymptomatic. Furthermore, given the neurotropic characteristics of the virus, studies aimed at understanding the complex pathogenesis in humans is difficult. As a result, animal models have been developed to understand several characteristics of HSV biology, pathogenesis, disease and host responses to infection. These models are also commonly used as the first evaluation of new drugs and vaccines. There are several well-established animal models to study infection with HSV, including mice, guinea pigs and rabbits. Variables within the animal models depend on the species of animal, route of infection, viral strain, dosage, etc. This review aims at summarizing the most commonly used animal models to study HSV pathogenesis and therapies.

One-pot synthesis, characterization and antiviral properties of new benzenesulfonamide-based spirothiazolidinones

A novel series of benzenesulfonamide substituted spirothiazolidinone derivatives (3a–j) were synthesized, characterized and evaluated for their antiviral activity. The spirocyclic compounds were prepared by the condensation of 4-(aminosulfonyl)-2-methoxybenzohydrazide, appropriate cyclic ketones and 2-mercaptopropionic acid in a one-pot reaction. The structures of the new compounds were established by IR, 1H NMR, 13C NMR (APT), and elemental analysis. The new compounds were evaluated in vitro antiviral activity against influenza A/H1N1, A/H3N2 and B viruses, as well as herpes simplex virus type 1 (HSV-1), respiratory syncytial virus (RSV) and yellow fever virus (YFV). Two derivatives bearing propyl (3d) and tert-butyl (3e) substituents at position 8 of the spiro ring exhibited activity against influenza A/H1N1 virus with EC50 values in the range of 35–45 µM and no cytotoxicity at 100 μM, the highest concentration tested.

Rapid NETosis Is an Effector Mechanism to Combat Ocular Herpes Infection.

Neutrophils are known mediators of innate immunity, yet their effector function in herpesvirus infections remains poorly understood. Here, we elucidate the mechanistic action and pivotal role of neutrophil extracellular traps (NETs) during herpes simplex virus type 1 (HSV-1) ocular infection. Neutrophils were collected from mice for HSV-1 infection, fluorescence imaging, and immunoblotting assay. Tear samples from healthy subjects and patients with HSV-1 and mice were collected at L. V. Prasad Eye Institute, India, and at the University of Illinois, USA, respectively. For the in vivo study, C57BL/6 mice as well as diversity outbred mice were infected with HSV-1 (McKrae strain) followed by tear fluid collection at various time points (0-10 days). Samples were used for Flow cytometry, ELISA, and immunofluorescence assay. Human transcriptomic profile of keratitis dataset was used evaluate NETosis signaling pathways. We also performed neutrophil depletion studies. Our data revealed a discernible temporal NET formation (NETosis) predominantly in the infected eye, across normal and diversity outbred murine models and human cases of HSV-1 infection. HSV-1 instigates swift NETosis governed by caspase-1 activation and myeloperoxidase secretion. Distinct accumulations of neutrophils, remaining unengaged in NET release in the contralateral eye post-infection, hinting at a proactive defensive posture in the uninfected eye. Moreover, neutrophil depletion accentuated ocular pathology, augmented viral load, and escalated disease scores, substantiating the protective effects of NETs in curtailing viral replication. Our report uncovers a previously unexplored mechanism of NETosis through pro-inflammatory cell death in response to ocular HSV-1 infection, and HPSE up-regulation, identifying new avenues for future studies.

A case for implementing an HSV1/2, VZV, and syphilis lesion panel in Manitoba, Canada.

Syphilis, caused by Treponema pallidum subsp. pallidum (TPA), is becoming a significant public health concern, with rising incidence in Manitoba exceeding the national average. The province has also seen a demographic shift leading to women representing 51.9% of cases in 2021, leading to the re-emergence of congenital syphilis. Given the similarities in lesion appearance between TPA and other pathogens such as herpesviruses, accurate diagnosis is crucial for effective management and prevention. In order to address the potential for missed TPA cases, we conducted a quality assurance study from June 2021 to March 2023, screening over 5,000 mucocutaneous lesion swabs for TPA, initially submitted for herpes simplex virus (HSV) and varicella zoster virus (VZV) testing. Positivity rates were 13% for HSV1, 13% for HSV2, 6.7% for VZV, and 6.6% for TPA. Turnaround times (TAT) for TPA testing, as a send-out to the reference laboratory, averaged 17.8 days. Of the TPA-positive specimens, 36% did not have a corresponding TPA PCR test ordered, and 19% did not have accompanying syphilis serology within 30 days of collection. Creation of a multiplex lesion panel identified high sensitivity and specificity for HSV1, HSV2, VZV, and TPA, with robust reproducibility across multiple runs. Incorporation of TPA into a lesion panel improved the TAT to 4 days. Our findings emphasize the need for improved testing strategies to combat the syphilis epidemic and enhance public health outcomes.IMPORTANCESyphilis resurgence has become a significant global public health concern. In particular, the Canadian Prairies have been struggling with high incidence since 2016, exceeding the national Canadian average. We undertook a quality assurance study that highlighted significant gaps in diagnosis of acute syphilis, which led to the development of a highly sensitive and specific multiplex lesion assay for the dual detection of herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), varicella zoster virus (VZV), and syphilis.

Overexpression of NLRP12 enhances antiviral immunity and alleviates herpes simplex keratitis via pyroptosis/IL-18/IFN-γ signaling

Herpes simplex keratitis (HSK) is a blinding disease caused by herpes simplex virus type 1 (HSV-1) infection, and rapid eradication of the virus from the affected cornea is imperative. Nod-like receptors (NLRs) are intracellular innate immune sensors closely associated with cell death, inflammation and immune responses. In this study, we investigated the role of NLRP12 in the antiviral immunology in HSK and the underlying mechanisms. We found that NLRP12 expression was significantly decreased in HSV-1-infected human corneal epithelial cells (HCE-Ts) and HSK mouse corneas. Overexpression of NLRP12 significantly reduced viral replication in infected HCE-Ts and functioned through inflammasome-mediated pyroptosis and downstream IL-18-IFN-γ axis. In HSK mouse models, overexpression of NLRP12 reduced viral replication in the cornea and alleviated HSK symptoms. This resulted from enhanced antiviral immune responses including the activation of specific immune cells in both the cornea and the draining lymph nodes. Specifically, the NLRP12-IL-18-IFN-γ axis regulated the interaction between infected corneal epithelial cells and macrophages. In conclusion, our study identified a role of NLRP12 in mediating pyroptosis and regulating antiviral immune responses. This novel finding opens the possibilities of NLRP12 as a viable target in the therapeutic strategies for HSV-1 infection.

The Topical Novel Formulations of Interferon α-2в Effectively Inhibit HSV-1 Keratitis in the Rabbit Eye Model and HSV-2 Genital Herpes in Mice.

Herpes simplex viruses type 1 (HSV-1) and type 2 (HSV-2) are widespread human pathogens that establish chronic latent infections leading to recurrent episodes. Current treatments are limited, necessitating the development of novel antiviral strategies. This study aimed to assess the antiviral efficacy of novel topical formulations containing interferon alpha-2b (IFN α-2b) against HSV-1 and HSV-2. The formulations, Oftalmoferon® forte (eye drops) and Interferon Vaginal Tablets, demonstrated potent antiviral effects against HSV-1 and HSV-2 in Vero cells, respectively, with concentration-dependent inhibition of viral replication. Subsequently, their efficacy was tested in animal models: HSV-1 keratitis in the rabbit eye model and HSV-2 genital herpes in mice. Oftalmoferon® forte effectively treated HSV-1 keratitis, reducing clinical symptoms and ulcerations compared to virus control. Interferon Vaginal Tablets showed promising results in controlling HSV-2 genital herpes in mice, improving survival rates, reducing clinical signs, weight loss and viral replication. The novel IFN α-2b formulations exhibited significant antiviral activity against HSV infections in cell culture and animal models. These findings suggest the potential of these formulations as alternative treatments for HSV infections, particularly in cases resistant to current therapies. Further studies are warranted to optimize treatment regimens and assess clinical efficacy in humans.

Development of an HSV-1 production process involving serum-reduced culturing and bead-to-bead transfer

Herpes simplex virus type 1 (HSV-1) plays an important role in the field of gene therapy and viral vaccines, especially as an oncolytic virus. However, the mass production of HSV-1 viral vectors remains a challenge in the industry. In this study, a microcarrier-mediated serum-reduced medium culture was used to improve the bioprocess of HSV-1 production and increase HSV-1 yields. The composition of the culture media, which included a basal medium, serum concentration, and glutamine additive, was optimized. The process was successfully conducted in a 1 L bioreactor, and virus production was threefold greater than that of conventional processes with a 10% serum medium. The bead-to-bead transfer process was also developed to further increase scalability. In spinner flasks, the detachment rate increased from 49.4 to 80.6% when combined agitation was performed during digestion; the overall recovery proportion increased from 37.9 to 71.1% after the operational steps were optimized. Specifically, microcarrier loss was reduced during aspiration and transfer, and microcarriers and detached cells were separated with filters. Comparable cell growth was achieved with the baseline process using 2D culture as the inoculum by exchanging the subculture medium. To increase virus production after bead-to-bead transfer, critical parameters, including shear stress during digestion, TrypLE and EDTA concentrations in the subculture, and the CCI, were identified from 47 parameters via correlation analysis and principal component analysis. The optimized bead-to-bead transfer process achieved an average of 90.4% overall recovery and comparable virus production compared to that of the baseline process. This study is the first to report the optimization of HSV-1 production in Vero cells cultured on microcarriers in serum-reduced medium after bead-to-bead transfer.Key points• An HSV-1 production process was developed that involves culturing in serum-reduced medium, and this process achieved threefold greater virus production than that of traditional processes.• An indirect bead-to-bead transfer process was developed with over 90% recovery yield in bioreactors.• HSV-1 production after bead-to-bead transfer was optimized and was comparable to that achieved with 2D culture as inoculum.

Advances in the immunoescape mechanisms exploited by alphaherpesviruses.

Alphaherpesviruses, categorized as viruses with linear DNA composed of two complementary strands, can potentially to induce diseases in both humans and animals as pathogens. Mature viral particles comprise of a core, capsid, tegument, and envelope. While herpesvirus infection can elicit robust immune and inflammatory reactions in the host, its persistence stems from its prolonged interaction with the host, fostering a diverse array of immunoescape mechanisms. In recent years, significant advancements have been achieved in comprehending the immunoescape tactics employed by alphaherpesviruses, including pseudorabies virus (PRV), herpes simplex virus (HSV), varicella-zoster virus (VZV), feline herpesvirus (FeHV), equine herpesvirus (EHV), and caprine herpesvirus type I (CpHV-1). Researchers have unveiled the intricate adaptive mechanisms existing between viruses and their natural hosts. This review endeavors to illuminate the research advancements concerning the immunoescape mechanisms of alphaherpesviruses by delineating the pertinent proteins and genes involved in virus immunity. It aims to furnish valuable insights for further research on related mechanisms and vaccine development, ultimately contributing to virus control and containment efforts.

Structural relationship of regioselectively-sulfonated botryosphaeran derivatives on activity against herpes simplex virus type 1

The bioactivities of sulfonated polysaccharides are frequently related to their substitution pattern. In this study, the regioselective sulfonation of an exocellular fungal (1→3)(1→6)-β-D-glucan (botryosphaeran) was performed by two different methods: mild sulfonation (MS) and via pivaloyl ester (PS), in order to study the influence of the sulfonation pattern on the antiviral activity of the respective derivatives. Two sulfonated derivatives with substitution degrees of 0.82 (MS) and 0.49 (PS) were obtained, with substitution patterns at positions C-6, and C-2/C-4 of the glucose units, respectively. All derivatives were chemically characterized and evaluated for antiviral activity against Herpes simplex virus type 1 (HSV-1) KOS strain, and dengue type 2 (DENV-2). The sample sulfonated at positions C-6 (MS) showed a remarkable antiviral effect on HSV-1 (IC50 of 5.38 μg mL1), while PS remained inactive. The investigation of the mode of action of sample MS pointed to the inhibition of HSV-1 adsorption to the host cells. Both samples were inactive towards the dengue virus strain. This study demonstrated that the presence of sulfate groups at the C-6 positions of botryosphaeran is the preferred substitution pattern that enables the antiviral activity towards HSV-1.

Antiviral activity of temporin-1CEb analogues against gingival infection with herpes simplex virus type 1.

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. 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. 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.

α7 nicotinic receptor activation mitigates herpes simplex virus type 1 infection in microglia cells

Herpes simplex virus type 1 (HSV-1), a neurotropic DNA virus, establishes latency in neural tissues, with reactivation causing severe consequences like encephalitis. Emerging evidence links HSV-1 infection to chronic neuroinflammation and neurodegenerative diseases. Microglia, the central nervous system's (CNS) immune sentinels, express diverse receptors, including α7 nicotinic acetylcholine receptors (α7 nAChRs), critical for immune regulation. Recent studies suggest α7 nAChR activation protects against viral infections. Here, we show that α7 nAChR agonists, choline and PNU-282987, significantly inhibit HSV-1 replication in microglial BV2 cells. Notably, this inhibition is independent of the traditional ionotropic nAChR signaling pathway. mRNA profiling revealed that choline stimulates the expression of antiviral factors, IL-1β and Nos2, and down-regulates the apoptosis genes and type A Lamins in BV2 cells. These findings suggest a novel mechanism by which microglial α7 nAChRs restrict viral infections by regulating innate immune responses.

Diagnostic Significance Vasoendothelial Growth Factor Depending on the Severity and Duration of Atopic Dermatitis, as Well as Taking into Account the Presence of Markers of Herpes Virus Infection

Currently, the problem of diagnosis and treatment of diseases associated with disorders of the angiogenesis process, as well as regenerative processes, is acute. Factors regulating the processes of angiogenesis in allergic diseases, including atopic dermatitis, play a key role in maintaining chronic inflammation and can have a significant impact on the course of the disease. Materials and methods: The study is analytical cross-sectional and presented by a comprehensive examination of 140 patients with AtD aged 2 to 12 years (median age 4.2 years), divided into 2 groups: 70 children with an established diagnosis of AtD; 70 children with atopic dermatitis infected with herpes simplex virus (AtD+HVI). The control group consisted of 70 somatically healthy children. A special laboratory examination included the determination of specific IgM and/or IgG class antibodies to herpes simplex virus type 1-2 antigens by enzyme immunoassay (ELISA); determination of the DNA of the studied herpesviruses in blood samples by polymerase chain reaction; determination of vascular endothelial growth factor A (VEGF-A) in the blood plasma of patients by ELISA. The results of our own research: A statistically significant (p <0.001) increase in the level of vascular endothelial growth factor A in blood serum was found in children with AtD compared with the control group. Against the background of infection with the herpes simplex virus, an increase in the level of vascular endothelial growth factor A in blood serum was revealed compared with patients with atopic dermatitis (p < 0.001). There was also a statistically significant increase in serum VEGF-A levels in patients with AtD (p < 0.001) and AtD+HVI (p < 0.001) with an increase in the severity of AtD. This was confirmed by the results of a correlation analysis that revealed the relationship between the level of VEGF-A and the severity of clinical symptoms of the disease.The addition of herpesvirus infection to AtD worsens the clinical symptoms of this disease.

Fluorescent octahydrophenazines as novel inhibitors against herpes simplex viruses

A new series of racemic fluorescent octahydrophenazines (rac-PZ1–11) have been designed and synthesized via the efficient nucleophilic aromatic substitution (SNAr) of tetrafluorobenzenedinitriles (1a–c) and racemic cyclohexane-1,2-diamines (rac-2a and b). The bioactivities of these racemic rac-PZs (20 μM) against herpes simplex virus type-1 (HSV-1) were evaluated by the relative cell viability of Vero cells infected with HSV-1. It was found that rac-PZ3 shows much higher anti-HSV-1 activity than others, with EC50 = 9.2 ± 1.4 μM. Further investigation into the anti-HSV activities of rac-PZ3 and its enantiomers RR- and SS-PZ3 indicates that rac-PZ3 can also efficiently inhibit HSV-2 and even ACV-resistant HSV-2 (EC50 = 11.0 ± 2.3 and 14.9 ± 2.8 μM, respectively), SS-PZ3 has better activities against HSV-1, HSV-2 and ACV-resistant HSV-2 (EC50 = 4.1 ± 1.1, 5.8 ± 1.0 and 7.9 ± 1.2 μM, respectively), but RR-PZ3 has almost no antiviral activities. The primary mechanism study indicates that rac-PZ3 efficiently reverses the HSV-1/2-induced cytopathic effect and suppresses the expression of viral mRNA and proteins. In addition, rac-, RR- and SS-PZ3 possess excellent fluorescence properties with almost the same emission wavelength and high fluorescence quantum yields (ΦF = 90.3–92.3 % in cyclohexane solutions and 54.4–57.3 % in solids) and can target endoplasmic reticulum and cell membrane. The efficient anti-HSV bioactivities and excellent fluorescence of PZ3 prove its potential applications in antiviral therapy and biological imaging.