Pseudorabies virus uses clathrin mediated endocytosis to enter PK15 swine cell line.

Pseudorabies virus (PRV), a herpesvirus responsible for Aujeszky's disease, causes high mortality in swine populations. To develop effective and novel antiviral strategies, it is essential to understand the mechanism of entry used by PRV to infect its host. Viruses have different ways of entering host cells. Among others, they can use endocytosis, a fundamental cellular process by which substances from the external environment are internalized into the cell. This process is classified into clathrin-mediated endocytosis (CME) and clathrin-independent endocytosis (CIE), depending on the role of clathrin. Although the involvement of cholesterol-rich lipid rafts in the entry of PRV has already been described, the importance of other endocytic pathways involving clathrin remains unexplored to date. Here, we characterize the role of CME in PRV entry into the PK15 swine cell line. By using CME inhibitory drugs, we report a decrease in PRV infection when the CME pathway is blocked. We also perform the shRNA knockdown of the µ-subunit of the adaptor protein AP-2 (AP2M1), which plays an important role in the maturation of clathrin-coated vesicles, and the infection is greatly reduced when this subunit is knocked down. Furthermore, transmission electron microscopy images report PRV virions inside clathrin-coated vesicles. Overall, this study suggests for the first time that CME is a mechanism used by PRV to enter PK15 cells and provides valuable insights into its possible routes of entry.

Suppression of sweet taste-related responses by plant-derived bioactive compounds and eating. Part II: A systematic review in animals.

This article, the second in a two-part series, continues the discussion on the nature of the relationship between the level of sweet taste suppression and eating behaviour, but in animal rather human subjects. In particular, the aim was to review the scientific literature on the impact that bioactive compounds that decrease oral sweet sensations have on intake, preference and physiological status in preclinical studies. This review was registered in the International Prospective Register of Systematic Reviews and conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Scottish Intercollegiate Guidelines Network and covered original papers included in Web of Science, PubMed, Scopus, Food Science Source and Food Science and technology abstracts. We identified 28 peer-reviewed English-language studies that fit the topic and met the inclusion criteria. We identified three plant species, Gymnema sylvestre, Hovenia dulcis, and Ziziphus jujuba, that possess acute sweetness-inhibitory properties. When administered orally, these plants reduced neural responses to sweet stimuli and decreased consumption. However, studies on the longer-term effects of antisweet activity remain to be conducted. Translating the valuable insights into the mechanisms underlying the relationship between sweet taste impairment and eating behaviour into practical clinical applications are discussed.

Suppression of sweet taste-related responses by plant-derived bioactive compounds and eating. Part I: A systematic review in humans.

The taste of food plays a crucial role in determining what and how much we eat. Thus, interventions that temporarily block sweet taste receptors offer a promising approach to addressing unhealthy behaviours associated with sugary foods. However, the relationship between reduced sweet taste response and food consumption remains unclear, with contradictory findings. Certain studies suggest that a diminished perception of sweetness leads to a sense of fullness and results in reduced food intake, while others suggest the opposite effect. To shed some light, our systematic review looked into the relationship between diminished sweet taste response and food consumption by examining the effects of bioactive compounds that experimentally inhibit sweetness in healthy individuals. This review was registered in the International Prospective Register of Systematic Reviews and conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Scottish Intercollegiate Guidelines Network, and covered original papers included in Web of Science, PubMed, Scopus, Food Science Source and Food Science and technology abstracts. We identified 33 peer-reviewed English-language studies that fit the topic and met the inclusion criteria. The current literature predominantly focuses on the immediate impact of oral gymnemic acids, failing to provide preliminary evidence in support of the specific threshold hypothesis, above which food consumption decreases and below which the opposite effect occurs. Additionally, there was inconsistency in the findings regarding the short-term desire to eat following sweetness inhibition. Considering the downstream effects on energy intake and their clinical applications, further research is needed to clarify both the acute within-session effects (i.e., not wanting any more now) and the longer-term effects (i.e., deciding not to start eating) linked to oral sweet-taste-suppressing compounds.

Is the Development of Ascites in Alcoholic Liver Patients Influenced by Specific KIR/HLA Gene Profiles?

Decompensated cirrhosis is the most common cause of ascites due to hemodynamic and renal alteration by continuous fluid leakage from the hepatic sinusoids and splanchnic capillaries into the interstitial space. Then, fluid leakage exceeds lymphatic return, leading to progressive fluid accumulation directly into the peritoneal cavity. Alcohol consumption is one of the main risks of developing alcoholic cirrhosis (AC), but not all AC patients develop ascites. Avoiding the development of ascites is crucial, given that it deteriorates prognosis and increases the patient mortality patient. The innate immune system plays a crucial role in cirrhosis through natural killer cells, which are abundant in the liver. The aim of this study was to analyze the KIR/HLA-C genetic profile in AC patients with and without ascites to understand this pathology and find predictive clinical susceptibility biomarkers that can help to establish risks and prevent the development of ascites in AC patients. A total of 281 AC patients with and without ascites were analyzed and compared with 319 healthy controls. Genomic DNA was extracted from peripheral blood in all groups. A PCR-SSO assay was performed for KIR/HLA genotyping analysis. A total of 16 activating and inhibitor KIR genes and their corresponding known ligands, epitopes of HLA-C, and their genotypes were analyzed. According to our analysis, C1 epitopes were statistically significantly decreased in AC patients with and without ascites. When comparing AC patients with ascites and healthy controls, a significant decrease in C1 epitope frequency was also observed. A statistically significant decrease was also found when comparing the C1C2 genotype in AC patients without ascites with controls. In conclusion, the absence of KIR2DL2 and KIR3DL1 genes may be a predisposing factor for the development of ascites in AC patients. The KIR2DS2/KIR2DL2 may could be involved in grade I ascites development, and the presence of the C1+ epitope and the homozygous C2C2 genotype may be protective genetic factors against ascites development in AC patients.

EVC-EVC2 complex stability and ciliary targeting are regulated by modification with ubiquitin and SUMO.

Ellis van Creveld syndrome and Weyers acrofacial dysostosis are two rare genetic diseases affecting skeletal development. They are both ciliopathies, as they are due to malfunction of primary cilia, microtubule-based plasma membrane protrusions that function as cellular antennae and are required for Hedgehog signaling, a key pathway during skeletal morphogenesis. These ciliopathies are caused by mutations affecting the EVC-EVC2 complex, a transmembrane protein heterodimer that regulates Hedgehog signaling from inside primary cilia. Despite the importance of this complex, the mechanisms underlying its stability, targeting and function are poorly understood. To address this, we characterized the endogenous EVC protein interactome in control and Evc-null cells. This proteomic screen confirmed EVC's main known interactors (EVC2, IQCE, EFCAB7), while revealing new ones, including USP7, a deubiquitinating enzyme involved in Hedgehog signaling. We therefore looked at EVC-EVC2 complex ubiquitination. Such ubiquitination exists but is independent of USP7 (and of USP48, also involved in Hh signaling). We did find, however, that monoubiquitination of EVC-EVC2 cytosolic tails greatly reduces their protein levels. On the other hand, modification of EVC-EVC2 cytosolic tails with the small ubiquitin-related modifier SUMO3 has a different effect, enhancing complex accumulation at the EvC zone, immediately distal to the ciliary transition zone, possibly via increased binding to the EFCAB7-IQCE complex. Lastly, we find that EvC zone targeting of EVC-EVC2 depends on two separate EFCAB7-binding motifs within EVC2's Weyers-deleted peptide. Only one of these motifs had been characterized previously, so we have mapped the second herein. Altogether, our data shed light on EVC-EVC2 complex regulatory mechanisms, with implications for ciliopathies.

Enfermedades por priones humanas. Una revisión general / Human prion diseases: An overview

Las enfermedades por priones constituyen un grupo de enfermedades neurodegenerativas, cuyo agente causal es una proteína normal del cerebro (PrP) que se agrega en una conformación anómala. La proteína anormal, conocida como prion (PrPSc), tiene la propiedad de autopropagarse, induciendo la plegadura anómala de la proteína normal PrP. Estas enfermedades se presentan de manera esporádica, por transmisión genética, o de forma adquirida por ingesta de carne contaminada con priones o por exposición iatrógena. Su diagnóstico resulta difícil. La utilización de exploraciones complementarias de alta sensibilidad y especificidad, como la resonancia magnética o la RT-QuIC, facilitan su diagnóstico. El diagnóstico definitivo se establece por el estudio histopatológico de muestras de tejidos. Actualmente, no se dispone de ningún tratamiento que modifique el curso de la enfermedad, pero su diagnóstico precoz es fundamental para planificar los cuidados del enfermo, adoptar las medidas de prevención necesarias y el consejo genético (AU)

Prion diseases are a group of neurodegenerative diseases. The disease-causing agent is a protein (PrP), that is normally produced in the nervous system, aggregated in an abnormal form. The abnormal protein, known as prion (PrPSc), is capable of self-propagation promoting the misfolding of the normal protein (PrP). These conditions can be acquired sporadically, genetically, or infectiously either by eating meat contaminated with prions or from iatrogenic exposure. The diagnosis of these diseases is often challenging. The use of highly sensitive and specific diagnostic tools, such as MRI and RT-QuIC, may aid in the diagnosis. Neuropathological examination of brain tissue ensures a definite diagnosis. At present, no treatment significantly improves the course of prion diseases; however, an early diagnosis is of paramount importance for patient care decision planning, infection control purposes, and genetic counseling (AU)

Dextran sulfate from Leuconostoc mesenteroides B512F exerts potent antiviral activity against SARS-CoV-2 in vitro and in vivo.

The emergent human coronavirus SARS-CoV-2 and its resistance to current drugs makes the need for new potent treatments for COVID-19 patients strongly necessary. Dextran sulfate (DS) polysaccharides have long demonstrated antiviral activity against different enveloped viruses in vitro. However, their poor bioavailability has led to their abandonment as antiviral candidates. Here, we report for the first time the broad-spectrum antiviral activity of a DS-based extrapolymeric substance produced by the lactic acid bacterium Leuconostoc mesenteroides B512F. Time of addition assays with SARS-CoV-2 pseudoviruses in in vitro models confirm the inhibitory activity of DSs in the early stages of viral infection (viral entry). In addition, this exopolysaccharide substance also reports broad-spectrum antiviral activity against several enveloped viruses such as SARS-CoV-2, HCoV229E, HSV-1, in in vitro models and in human lung tissue. The toxicity and antiviral capacity of DS from L. mesenteroides was tested in vivo in mouse models which are susceptible to SARS-CoV-2 infection. The described DS, administered by inhalation, a new route of administration for these types of polymers, shows strong inhibition of SARS-CoV-2 infection in vivo, significantly reducing animal mortality and morbidity at non-toxic doses. Therefore, we suggest that it may be considered as a potential candidate for antiviral therapy against SARS-CoV-2.

Liposomal Lactoferrin Exerts Antiviral Activity against HCoV-229E and SARS-CoV-2 Pseudoviruses In Vitro.

A limited number of effective therapies are currently available to treat human coronavirus SARS-CoV-2 and other human coronaviruses, which are responsible for nearly a third of global cases of the common cold. The possibility of new emerging coronaviruses demands powerful new antiviral strategies. Lactoferrin is a well-known protein that possesses anti-inflammatory and immunomodulatory activities, and it has previously shown antiviral activity against several viruses, including SARS-CoV-2. To increase this antiviral activity, here we present bovine liposomal lactoferrin. Liposomal encapsulation of the compound was proven to increase permeability, bioavailability, and time release. In the present work, we compare the antiviral activity of free and liposomal bovine lactoferrin against HCoV229E and SARS-CoV-2 in vitro and in human primary bronchial epithelial cells, and we demonstrated that the liposomal form exerts a more potent antiviral activity than its free form at non-cytotoxic doses.

Presence of KIR2DL2/S2, KIR2DL5, and KIR3DL1 Molecules in Liver Transplant Recipients with Alcoholic Cirrhosis Could Be Implicated in Death by Graft Failure.

Background: The second-most frequent diagnosis among patients receiving liver transplants (LTs) is alcoholic liver disease. The multifactorial pathophysiology of alcoholic liver disease depends on the innate immune system and the inflammatory cascade. According to recent studies on these receptors, killer-cell immunoglobulin-like receptors (KIRs) may be involved in sepsis, liver rejection, and virus relapse. We aimed to investigate the impact of preclinical issues like ascites and encephalopathy and KIR genetic traits on death from sepsis, multiorgan failure (MF), and graft failure (GF) in AC patients undergoing LTs. Methods: We retrospectively reviewed 164 consecutive and deceased Caucasian AC patients who underwent LTs. Pre-transplant complications, cause of death, and patient survival were analyzed. Genomic DNA was taken from peripheral blood, and PCR-SSO was used for genotyping KIR. Results: Compared to GF patients, there was a statistically significant increase in the frequency of KIR2DL2+ (75.8% vs. 51.2%; p = 0.047). Another increase in frequency was also observed in KIR2DS2+ in sepsis compared to the GF group (51.2% vs. 43.7%; p = 0.018). In patients who passed away from MF, a decrease in KIR2DL5+ was observed in AC patients with and without encephalopathy (p = 0.018). The frequency of KIR3DL1+ in the AC patients significantly increased the mortality from sepsis (p = 0.045), which was confirmed by multivariate logistic regression. The frequency of KIR3DL1+ in the AC patients significantly increased the mortality from sepsis (p = 0.012) and was confirmed by multivariate logistic regression. KIR2DS1+ and KIR2DS4+ showed increased mortality due to GF compared to patients without these genes (p = 0.011 and 0.012, respectively). However, this fact was confirmed only for KIR2DS1+ by multivariate logistic Cox regression. Conclusions: The presence of the KIR2DL2/S2+, KIR2DL5+, and KIR3DL1+ genes increases the frequency of death from multiple organ failure or graft failure. Our findings highlight the AC patient's vulnerability to a LT during hospitalization. Following the transplant and outside of it, we adopt essential preventive measures to create a routine healthcare screening to enhance and modify treatments to increase survival.

[Human prion diseases: An overview]. / Enfermedades por priones humanas. Una revisión general.

Prion diseases are a group of neurodegenerative diseases. The disease-causing agent is a protein (PrP), that is normally produced in the nervous system, aggregated in an abnormal form. The abnormal protein, known as prion (PrPSc), is capable of self-propagation promoting the misfolding of the normal protein (PrP). These conditions can be acquired sporadically, genetically, or infectiously either by eating meat contaminated with prions or from iatrogenic exposure. The diagnosis of these diseases is often challenging. The use of highly sensitive and specific diagnostic tools, such as MRI and RT-QuIC, may aid in the diagnosis. Neuropathological examination of brain tissue ensures a definite diagnosis. At present, no treatment significantly improves the course of prion diseases; however, an early diagnosis is of paramount importance for patient care decision planning, infection control purposes, and genetic counseling.

Prevalence of Schistosoma haematobium and Intestinal Helminth Infections among Nigerian School Children.

Schistosomiasis and soil-transmitted helminthiases (STH) are two parasitic diseases mainly affecting school children. The purpose of this study was to estimate the current prevalence and infection intensity, in addition to the associations of these infections with age and sex, in children aged 4-17 years living in Osun State, Nigeria. From each participant (250 children), one urine and one stool sample were taken for the study, for the microscopic detection of eggs or larvae in faeces by means of the Kato-Katz method and eggs in filtrated urine. The overall prevalence of urinary schistosomiasis was 15.20%, with light infection. The intestinal helminthic species identified (and their prevalence) were S. stercoralis (10.80%), S. mansoni (8%), A. lumbricoides (7.20%), hookworm (1.20%), and T. trichiura (0.4%), all of them being classified as light infections. Single infections (67.95%) are more frequent than multiple infections (32.05%). With this study, schistosomiasis and STH are still endemic in Osun State, but with a light to moderate prevalence and light infection intensity. Urinary infection was the most prevalent, with higher prevalence in children over 10 years. The >10 years age group had the highest prevalence for all of the intestinal helminths. There were no statistically significant associations between gender and age and urogenital or intestinal parasites.

Potent Virucidal Activity In Vitro of Photodynamic Therapy with Hypericum Extract as Photosensitizer and White Light against Human Coronavirus HCoV-229E.

The emergent human coronavirus SARS-CoV-2 and its high infectivity rate has highlighted the strong need for new virucidal treatments. In this sense, the use of photodynamic therapy (PDT) with white light, to take advantage of the sunlight, is a potent strategy for decreasing the virulence and pathogenicity of the virus. Here, we report the virucidal effect of PDT based on Hypericum extract (HE) in combination with white light, which exhibits an inhibitory activity of the human coronavirus HCoV-229E on hepatocarcinoma Huh-7 cells. Moreover, despite continuous exposure to white light, HE has long durability, being able to maintain the prevention of viral infection. Given its potent in vitro virucidal capacity, we propose HE in combination with white light as a promising candidate to fight against SARS-CoV-2 as a virucidal compound.

Interplay between Autophagy and Herpes Simplex Virus Type 1: ICP34.5, One of the Main Actors.

Herpes simplex virus type 1 (HSV-1) is a neurotropic virus that occasionally may spread to the central nervous system (CNS), being the most common cause of sporadic encephalitis. One of the main neurovirulence factors of HSV-1 is the protein ICP34.5, which although it initially seems to be relevant only in neuronal infections, it can also promote viral replication in non-neuronal cells. New ICP34.5 functions have been discovered during recent years, and some of them have been questioned. This review describes the mechanisms of ICP34.5 to control cellular antiviral responses and debates its most controversial functions. One of the most discussed roles of ICP34.5 is autophagy inhibition. Although autophagy is considered a defense mechanism against viral infections, current evidence suggests that this antiviral function is only one side of the coin. Different types of autophagic pathways interact with HSV-1 impairing or enhancing the infection, and both the virus and the host cell modulate these pathways to tip the scales in its favor. In this review, we summarize the recent progress on the interplay between autophagy and HSV-1, focusing on the intricate role of ICP34.5 in the modulation of this pathway to fight the battle against cellular defenses.

Multiple ciliary localization signals control INPP5E ciliary targeting.

Primary cilia are sensory membrane protrusions whose dysfunction causes ciliopathies. INPP5E is a ciliary phosphoinositide phosphatase mutated in ciliopathies like Joubert syndrome. INPP5E regulates numerous ciliary functions, but how it accumulates in cilia remains poorly understood. Herein, we show INPP5E ciliary targeting requires its folded catalytic domain and is controlled by four conserved ciliary localization signals (CLSs): LLxPIR motif (CLS1), W383 (CLS2), FDRxLYL motif (CLS3) and CaaX box (CLS4). We answer two long-standing questions in the field. First, partial CLS1-CLS4 redundancy explains why CLS4 is dispensable for ciliary targeting. Second, the essential need for CLS2 clarifies why CLS3-CLS4 are together insufficient for ciliary accumulation. Furthermore, we reveal that some Joubert syndrome mutations perturb INPP5E ciliary targeting, and clarify how each CLS works: (i) CLS4 recruits PDE6D, RPGR and ARL13B, (ii) CLS2-CLS3 regulate association to TULP3, ARL13B, and CEP164, and (iii) CLS1 and CLS4 cooperate in ATG16L1 binding. Altogether, we shed light on the mechanisms of INPP5E ciliary targeting, revealing a complexity without known parallels among ciliary cargoes.

Pharmacogenetics of siponimod: A systematic review.

Multiple sclerosis is a chronic inflammatory neurological disease, and siponimod (Mayzent) is the first oral treatment option for adult patients with secondary progressive multiple sclerosis. We performed a systematic review of the pharmacogenetics of Siponimod, and we found that (430 C>T; rs1799853) and CYP2C9 * 3 (1075 A>C; rs1057910), both translated no-function alleles, have been related to a lower metabolism of siponimod by CYP2C9 enzyme. The FDA-approved drug label and EMA risk management plan for siponimod require testing patients for CYP2C9 genotype before treatment starts. The FDA drug label states that siponimod is contraindicated in patients carrying a CYP2C9 * 3/* 3 genotype, and a daily maintenance dose of 1 mg in patients with CYP2C9 * 1/* 3 and * 2/* 3 genotypes. The EMA reported the potential long-term safety implications in CYP2C9 poor metabolizer patients treated with this drug. Based on this systematic review we concluded that CYP2C9 SNPs influence on siponimod response might be stated by assessing not only CYP2C9 * 2 and CYP2C9 * 3 but other genetic variants resulting in CYP2C9 IM/PM status. CYP2C9 IM phenotype translated from the CYP2C9 * 2 genotype should be revised since it is contradictory compared to other CYP2C9 no-function alleles, and CYP2C9 * 2 might be excluded from PGx testing recommendation before treatment starts with siponimod since it is not translated into a therapeutic recommendation.

Extracellular Polymeric Substances: Still Promising Antivirals.

Sulfated polysaccharides and other polyanions have been promising candidates in antiviral research for decades. These substances gained attention as antivirals when they demonstrated a high inhibitory effect in vitro against human immunodeficiency virus (HIV) and other enveloped viruses. However, that initial interest was followed by wide skepticism when in vivo assays refuted the initial results. In this paper we review the use of sulfated polysaccharides, and other polyanions, in antiviral therapy, focusing on extracellular polymeric substances (EPSs). We maintain that, in spite of those early difficulties, the use of polyanions and, specifically, the use of EPSs, in antiviral therapy should be reconsidered. We base our claim in several points. First, early studies showed that the main disadvantage of sulfated polysaccharides and polyanions is their low bioavailability, but this difficulty can be overcome by the use of adequate administration strategies, such as nebulization of aerosols to gain access to respiratory airways. Second, several sulfated polysaccharides and EPSs have demonstrated to be non-toxic in animals. Finally, these macromolecules are non-specific and therefore they might be used against different variants or even different viruses.

Progressive Multifocal Leukoencephalopathy and Immune Reconstitution Inflammatory Syndrome after Discontinuation of Fingolimod.

Progressive multifocal leukoencephalopathy (PML) is a rare complication of immunosuppressive treatment in MS patients. Immune reconstitution inflammatory syndrome (IRIS) appears after the withdrawal of certain drugs such as natalizumab (NTZ) or fingolimod. The development of PML-IRIS after NTZ treatment has been described, and its diagnosis is made by clinical and radiological criteria and the determination of the John Cunningham virus in CSF. We present a clinical case of a patient with MS who, after the withdrawal of fingolimod, developed PML-IRIS despite sustained lymphopenia. This is important for pharmacovigilance purposes, not only for NTZ but also for alternative drugs used in MS treatment.

Clinical and Laboratory Features in Anti-NF155 Autoimmune Nodopathy.

BACKGROUND AND OBJECTIVES: To study the clinical and laboratory features of antineurofascin-155 (NF155)-positive autoimmune nodopathy (AN). METHODS: Patients with anti-NF155 antibodies detected on routine immunologic testing were included. Clinical characteristics, treatment response, and functional scales (modified Rankin Scale [mRS] and Inflammatory Rasch-built Overall Disability Scale [I-RODS]) were retrospectively collected at baseline and at the follow-up. Autoantibody and neurofilament light (NfL) chain levels were analyzed at baseline and at the follow-up. RESULTS: Forty NF155+ patients with AN were included. Mean age at onset was 42.4 years. Patients presented with a progressive (75%), sensory motor (87.5%), and symmetric distal-predominant weakness in upper (97.2%) and lower extremities (94.5%), with tremor and ataxia (75%). Patients received a median of 3 (2-4) different treatments in 46 months of median follow-up. Response to IV immunoglobulin (86.8%) or steroids (72.2%) was poor in most patients, whereas 77.3% responded to rituximab. HLA-DRB1*15 was detected in 91.3% of patients. IgG4 anti-NF155 antibodies were predominant in all patients; anti-NF155 titers correlated with mRS within the same patient (r = 0.41, p = 0.004). Serum NfL (sNfL) levels were higher in anti-NF155+ AN than in healthy controls (36.47 vs 7.56 pg/mL, p < 0.001) and correlated with anti-NF155 titers (r = 0.43, p = 0.001), with I-RODS at baseline (r = -0.88, p < 0.001) and with maximum I-RODS achieved (r = -0.58, p = 0.01). Anti-NF155 titers and sNfL levels decreased in all rituximab-treated patients. DISCUSSION: Anti-NF155 AN presents a distinct clinical profile and good response to rituximab. Autoantibody titers and sNfL are useful to monitor disease status in these patients. The use of untagged-NF155 plasmids minimizes the detection of false anti-NF155+ cases. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that anti-NF155 antibodies associate with a specific phenotype and response to rituximab.

The Valproic Acid Derivative Valpromide Inhibits Pseudorabies Virus Infection in Swine Epithelial and Mouse Neuroblastoma Cell Lines.

Pseudorabies virus (PRV) infection of swine can produce Aujeszky's disease, which causes neurological, respiratory, and reproductive symptoms, leading to significant economic losses in the swine industry. Although humans are not the natural hosts of PRV, cases of human encephalitis and endophthalmitis caused by PRV infection have been reported between animals and workers. Currently, a lack of specific treatments and the emergence of new PRV strains against which existing vaccines do not protect makes the search for effective antiviral drugs essential. As an alternative to traditional nucleoside analogues such as acyclovir (ACV), we studied the antiviral effect of valpromide (VPD), a compound derived from valproic acid, against PRV infection in the PK15 swine cell line and the neuroblastoma cell line Neuro-2a. First, the cytotoxicity of ACV and VPD in cells was compared, demonstrating that neither compound was cytotoxic at a specific concentration range after 24 h exposure. Furthermore, the lack of direct virucidal effect of VPD outside of an infected cell environment was demonstrated. Finally, VPD was shown to have an antiviral effect on the viral production of two strains of pseudorabies virus (wild type NIA-3 and recombinant PRV-XGF) at the concentrations ranging from 0.5 to 1.5 mM, suggesting that VPD could be a suitable alternative to nucleoside analogues as an antiherpetic drug against Aujeszky's disease.