Skin tropism during Usutu virus and West Nile virus infection: an amplifying and immunological role.

Usutu virus (USUV) and West Nile virus (WNV) are closely related emerging arboviruses belonging to the Flavivirus genus and posing global public health concerns. Although human infection by these viruses is mainly asymptomatic, both have been associated with neurological disorders such as encephalitis and meningoencephalitis. Since USUV and WNV are transmitted through the bite of an infected mosquito, the skin represents the initial site of virus inoculation and provides the first line of host defense. Although some data on the early stages of WNV skin infection are available, very little is known about USUV. Herein, USUV-skin resident cell interactions were characterized. Using primary human keratinocytes and fibroblasts, an early replication of USUV during the first 24 hours was shown in both skin cells. In human skin explants, a high viral tropism for keratinocytes was observed. USUV infection of these models induced type I and III interferon responses associated with upregulated expression of various interferon-stimulated genes as well as pro-inflammatory cytokine and chemokine genes. Among the four USUV lineages studied, the Europe 2 strain replicated more efficiently in skin cells and induced a higher innate immune response. In vivo, USUV and WNV disseminated quickly from the inoculation site to distal cutaneous tissues. In addition, viral replication and persistence in skin cells were associated with an antiviral response. Taken together, these results provide a better understanding of the pathophysiology of the early steps of USUV infection and suggest that the skin constitutes a major amplifying organ for USUV and WNV infection.IMPORTANCEUsutu virus (USUV) and West Nile virus (WNV) are closely related emerging Flaviviruses transmitted through the bite of an infected mosquito. Since they are directly inoculated within the upper skin layers, the interactions between the virus and skin cells are critical in the pathophysiology of USUV and WNV infection. Here, during the early steps of infection, we showed that USUV can efficiently infect two human resident skin cell types at the inoculation site: the epidermal keratinocytes and the dermal fibroblasts, leading to the induction of an antiviral innate immune response. Moreover, following cutaneous inoculation, we demonstrated that both viruses can rapidly spread, replicate, and persist in all distal cutaneous tissues in mice, a phenomenon associated with a generalized skin inflammatory response. These results highlight the key amplifying and immunological role of the skin during USUV and WNV infection.

Anti-SARS-CoV-2 Activity of Polysaccharides Extracted from Halymenia floresii and Solieria chordalis (Rhodophyta).

Even after hundreds of clinical trials, the search for new antivirals to treat COVID-19 is still relevant. Carrageenans are seaweed sulfated polysaccharides displaying antiviral activity against a wide range of respiratory viruses. The objective of this work was to study the antiviral properties of Halymenia floresii and Solieria chordalis carrageenans against SARS-CoV-2. Six polysaccharide fractions obtained from H. floresii and S. chordalis by Enzyme-Assisted Extraction (EAE) or Hot Water Extraction (HWE) were tested. The effect of carrageenan on viral replication was assessed during infection of human airway epithelial cells with a clinical strain of SARS-CoV-2. The addition of carrageenans at different times of the infection helped to determine their mechanism of antiviral action. The four polysaccharide fractions isolated from H. floresii displayed antiviral properties while the S. chordalis fractions did not. EAE-purified fractions caused a stronger reduction in viral RNA concentration. Their antiviral action is likely related to an inhibition of the virus attachment to the cell surface. This study confirms that carrageenans could be used as first-line treatment in the respiratory mucosa to inhibit the infection and transmission of SARS-CoV-2. Low production costs, low cytotoxicity, and a broad spectrum of antiviral properties constitute the main strengths of these natural molecules.

Distinct genetic basis for root responses to lipo-chitooligosaccharide signal molecules from different microbial origins.

Lipo-chitooligosaccharides (LCOs) were originally found as symbiotic signals called Nod Factors (Nod-LCOs) controlling the nodulation of legumes by rhizobia. More recently, LCOs were also found in symbiotic fungi and, more surprisingly, very widely in the kingdom Fungi, including in saprophytic and pathogenic fungi. The LCO-V(C18:1, fucosylated/methyl fucosylated), hereafter called Fung-LCOs, are the LCO structures most commonly found in fungi. This raises the question of how legume plants such as Medicago truncatula can discriminate between Nod-LCOs and Fung-LCOs. To address this question, we performed a genome-wide association study on 173 natural accessions of M. truncatula, using a root branching phenotype and a newly developed local score approach. Both Nod-LCOs and Fung-LCOs stimulated root branching in most accessions, but the root responses to these two types of LCO molecules were not correlated. In addition, the heritability of the root response was higher for Nod-LCOs than for Fung-LCOs. We identified 123 loci for Nod-LCO and 71 for Fung-LCO responses, of which only one was common. This suggests that Nod-LCOs and Fung-LCOs both control root branching but use different molecular mechanisms. The tighter genetic constraint of the root response to Fung-LCOs possibly reflects the ancestral origin of the biological activity of these molecules.

The Medicago truncatula LysM receptor-like kinase LYK9 plays a dual role in immunity and the arbuscular mycorrhizal symbiosis.

Plant -specific lysin-motif receptor-like kinases (LysM-RLKs) are implicated in the perception of N-acetyl glucosamine-containing compounds, some of which are important signal molecules in plant-microbe interactions. Among these, both lipo-chitooligosaccharides (LCOs) and chitooligosaccharides (COs) are proposed as arbuscular mycorrhizal (AM) fungal symbiotic signals. COs can also activate plant defence, although there are scarce data about CO production by pathogens, especially nonfungal pathogens. We tested Medicago truncatula mutants in the LysM-RLK MtLYK9 for their abilities to interact with the AM fungus Rhizophagus irregularis and the oomycete pathogen Aphanomyces euteiches. This prompted us to analyse whether A. euteiches can produce COs. Compared with wild-type plants, Mtlyk9 mutants had fewer infection events and were less colonised by the AM fungus. By contrast, Mtlyk9 mutants were more heavily infected by A. euteiches and showed more disease symptoms. Aphanomyces euteiches was also shown to produce short COs, mainly CO II, but also CO III and CO IV, and traces of CO V, both ex planta and in planta. MtLYK9 thus has a dual role in plant immunity and the AM symbiosis, which raises questions about the functioning and the ancestral origins of such a receptor protein.

Functional Consequences of RNA 5'-Terminal Deletions on Coxsackievirus B3 RNA Replication and Ribonucleoprotein Complex Formation.

Group B coxsackieviruses are responsible for chronic cardiac infections. However, the molecular mechanisms by which the virus can persist in the human heart long after the signs of acute myocarditis have abated are still not completely understood. Recently, coxsackievirus B3 strains with 5'-terminal deletions in genomic RNAs were isolated from a patient suffering from idiopathic dilated cardiomyopathy, suggesting that such mutant viruses may be the forms responsible for persistent infection. These deletions lacked portions of 5' stem-loop I, which is an RNA secondary structure required for viral RNA replication. In this study, we assessed the consequences of the genomic deletions observed in vivo for coxsackievirus B3 biology. Using cell extracts from HeLa cells, as well as transfection of luciferase replicons in two types of cardiomyocytes, we demonstrated that coxsackievirus RNAs harboring 5' deletions ranging from 7 to 49 nucleotides in length can be translated nearly as efficiently as those of wild-type virus. However, these 5' deletions greatly reduced the synthesis of viral RNA in vitro, which was detected only for the 7- and 21-nucleotide deletions. Since 5' stem-loop I RNA forms a ribonucleoprotein complex with cellular and viral proteins involved in viral RNA replication, we investigated the binding of the host cell protein PCBP2, as well as viral protein 3CDpro, to deleted positive-strand RNAs corresponding to the 5' end. We found that binding of these proteins was conserved but that ribonucleoprotein complex formation required higher PCBP2 and 3CDpro concentrations, depending on the size of the deletion. Overall, this study confirmed the characteristics of persistent CVB3 infection observed in heart tissues and provided a possible explanation for the low level of RNA replication observed for the 5'-deleted viral genomes-a less stable ribonucleoprotein complex formed with proteins involved in viral RNA replication.IMPORTANCE Dilated cardiomyopathy is the most common indication for heart transplantation worldwide, and coxsackie B viruses are detected in about one-third of idiopathic dilated cardiomyopathies. Terminal deletions at the 5' end of the viral genome involving an RNA secondary structure required for RNA replication have been recently reported as a possible mechanism of virus persistence in the human heart. These mutations are likely to disrupt the correct folding of an RNA secondary structure required for viral RNA replication. In this report, we demonstrate that transfected RNAs harboring 5'-terminal sequence deletions are able to direct the synthesis of viral proteins, but not genomic RNAs, in human and murine cardiomyocytes. Moreover, we show that the binding of cellular and viral replication factors to viral RNA is conserved despite genomic deletions but that the impaired RNA synthesis associated with terminally deleted viruses could be due to destabilization of the ribonucleoprotein complexes formed.

In vitro culture and phenotypic and molecular characterization of gastric stem cells from human stomach.

BACKGROUND: Human gastric mucosa shows continuous self-renewal via differentiation from stem cells that remain poorly characterized. METHODS: We describe an original protocol for culture of gastric stem/progenitor cells from adult human stomach. The molecular characteristics of cells were studied using TaqMan low-density array and qRT-PCR analyses using the well-characterized H1 and H9 embryonic stem cells as reference. Epithelial progenitor cells were challenged with H. pylori to characterize their inflammatory response. RESULTS: Resident gastric stem cells expressed specific molecular markers of embryonic stem cells (SOX2, NANOG, and OCT4), as well as others specific to adult stem cells, particularly LGR5 and CD44. We show that gastric stem cells spontaneously differentiate into epithelial progenitor cells that can be challenged with H. pylori. The epithelial progenitor response to H. pylori showed a cag pathogenicity island-dependent induction of matrix metalloproteinases 1 and 3, chemokine (CXCL1, CXCL5, CXCL8, CCL20) and interleukine 33 expression. CONCLUSION: This study opens new outlooks for investigation of gastric stem cell biology and pathobiology as well as host-H. pylori interactions.

Contemporary patterns of genetic diversity of cedrela fissilis offer insight into the shaping of seasonal forests in eastern South America.

PREMISE OF THE STUDY: We investigated how genetic diversity is distributed across the range of Cedrela fissilis, a tree species associated with seasonal neotropical forests, to gain insights into competing biogeographic scenarios that explain how disjunct distributions of these forests were shaped. METHODS: A total of 250 samples were sampled from 18 sites across the species' range in Brazil and eastern Bolivia and genotyped with 10 microsatellite loci. An array of complementary methods-F statistics, analyses of molecular variance (AMOVA), and clustering analyses-assessed genetic diversity, population differentiation, and structure. KEY RESULTS: Most of the genetic diversity (82.5%) was partitioned within populations, but about 12% was due to differences among groups of populations on either side of the Cerrado or located within the Cerrado; mean expected heterozygosity and mean observed heterozygosity were 0.821 and 0.704, respectively. The 250 samples were sorted into two Bayesian groups: one group for each side of the Cerrado. The populations showed varying levels of admixture, with the greatest admixture evident in populations located toward central Brazil. CONCLUSIONS: In C. fissilis, genetic diversity is structured according to geography: the Atlantic range and the Chiquitano range each harbor a genealogical lineage. Interfertility and varying levels of admixture between lineages provide strong evidence that the lineages evolved under geographic, but not genetic, isolation. Admixture is of recent origin, owing to population expansion. Cedrela fissilis shares this dual pattern of distribution of genetic diversity with other phylogenetically unrelated taxa that are typically associated with seasonal forests.

Chemokines and antimicrobial peptides have a cag-dependent early response to Helicobacter pylori infection in primary human gastric epithelial cells.

Helicobacter pylori infection systematically causes chronic gastric inflammation that can persist asymptomatically or evolve toward more severe gastroduodenal pathologies, such as ulcer, mucosa-associated lymphoid tissue (MALT) lymphoma, and gastric cancer. The cag pathogenicity island (cag PAI) of H. pylori allows translocation of the virulence protein CagA and fragments of peptidoglycan into host cells, thereby inducing production of chemokines, cytokines, and antimicrobial peptides. In order to characterize the inflammatory response to H. pylori, a new experimental protocol for isolating and culturing primary human gastric epithelial cells was established using pieces of stomach from patients who had undergone sleeve gastrectomy. Isolated cells expressed markers indicating that they were mucin-secreting epithelial cells. Challenge of primary epithelial cells with H. pylori B128 underscored early dose-dependent induction of expression of mRNAs of the inflammatory mediators CXCL1 to -3, CXCL5, CXCL8, CCL20, BD2, and tumor necrosis factor alpha (TNF-α). In AGS cells, significant expression of only CXCL5 and CXCL8 was observed following infection, suggesting that these cells were less reactive than primary epithelial cells. Infection of both cellular models with H. pylori B128ΔcagM, a cag PAI mutant, resulted in weak inflammatory-mediator mRNA induction. At 24 h after infection of primary epithelial cells with H. pylori, inflammatory-mediator production was largely due to cag PAI substrate-independent virulence factors. Thus, H. pylori cag PAI substrate appears to be involved in eliciting an epithelial response during the early phases of infection. Afterwards, other virulence factors of the bacterium take over in development of the inflammatory response. Using a relevant cellular model, this study provides new information on the modulation of inflammation during H. pylori infection.

Morphological, Biological, and Molecular Characterization of Type I Granuloviruses of Spodoptera frugiperda.

Granuloviruses (GVs) Betabaculovirus associated with the fall armyworm (FAW), Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae), especially those of the type I, have scarcely been studied. These GVs might be an effective alternative for the biocontrol of this insect. In this study, the native GVs SfGV-CH13 and SfGV-CH28 were isolated from FAW larvae and characterized for morphology, molecular traits, and insecticidal activity. The elapsed time between symptomatic infection of larvae and stop feeding as well as the weight of larvae before death or prior to pupation were also evaluated. Both GVs had ovoid shape and a length of 0.4 µm. They had the same DNA restriction profiles and their genome sizes were about 126 kb. The symptomatic infection with the tested GVs mainly caused flaccidity of larva body and discoloration of integument. The integument lysis was only observed in 8% of infected larvae. Infected larvae gradually stopped feeding. Overall, these symptoms are characteristic of infections caused by type I GVs, which are known as monoorganotropic or slow-killing GVs. The median lethal dose (LD50) values for SfGV-CH13 and SfGV-CH28 isolates were 5.4 × 102 and 1.1 × 103 OBs/larva, respectively. The median lethal time (LT50) ranged from 17 to 24 days. LT50 values decreased as the viral dose was increased. The elapsed time from symptomatic infection until pupation and body weight of larvae (third instar) were higher with SfGV-CH28 than SfGV-CH13. Both granulovirus isolates were able to kill the FAW larvae from the 12th day.

One year of SARS-CoV-2 circulation in the Nouvelle-Aquitaine region, February 2021-2022, France.

Background: Since 2021, 3 variants of concern (VOC) have spread to France, causing successive epidemic waves. Objectives: To describe the features of Alpha, Delta and Omicron VOC circulation in the Nouvelle-Aquitaine region, France, between February 2021 and February 2022. Study design: Data from the three university hospitals (UH) of Nouvelle-Aquitaine were used to describe regional SARS-CoV-2 circulation (RT-PCR positive rates and identified VOC) as well as its consequences (total number of hospitalizations and admissions in intensive care unit). They were analyzed according to the predominant variant and compared with national data. Results: A total of 611,106 SARS-CoV-2 RT-PCR tests were performed in the 3 Nouvelle-Aquitaine UH during the study period. The 37,750 positive samples were analyzed by variant-specific RT-PCR or whole-genome sequencing. In 2021, Alpha VOC was detected from week 5 until week 35. Delta became the most prevalent variant (77.3%) in week 26, reaching 100% in week 35. It was replaced by Omicron, which was initially detected week 48, represented 77% of positive samples in week 52 and was still predominant in February 2022. The RT-PCR positive rates were 4.3, 4.2, and 21.9% during the Alpha, Delta and Omicron waves, respectively. The ratio between intensive care unit admissions and total hospitalizations was lower during the Omicron wave than during the two previous waves due to the Alpha and Delta variants. Conclusion: This study highlighted the need for strong regional cooperation to achieve effective SARS-CoV-2 epidemiological surveillance, in close association with the public health authorities.

Effect of High Temperature and UV Radiation on the Insecticidal Capacity of a Spodoptera frugiperda Nucleopolyhedrovirus Microencapsulated in a Matrix Based on Oxidized Corn Starch.

A multiple nucleopolyhedrovirus native isolate (SfCH32) of Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae) was encapsulated by spray-drying in a matrix based on oxidized corn starch without and with a fluorescent brightener. The microcapsules were exposed to UV radiation (365 nm) for 0, 2, 4, and 8 h at 25 °C or temperatures of 35, 40, and 45 °C for 8 h. The data obtained with temperatures 35, 40, and 45 °C were contrasted with those obtained at 25 °C. The microcapsules were evaluated for size, shape, and insecticidal capacity against third instar S. frugiperda larvae under laboratory conditions. The 82-84.2% of the encapsulating matrix, in a dry-weight basis, was recovered as NPV microcapsules of heterogeneous shape and size. The exposure to UV radiation and temperatures reduced significantly the insecticidal capacity of tested viruses; however, such capacity was higher for microencapsulated than for non-microencapsulated viruses. The non-encapsulated virus that had been exposed to 45 °C or maintained at UV radiation for 8 h showed the lowest insecticidal activity at 5th day post-inoculation, with a larvae mortality of 25.3 and 16%, respectively. The fluorescent brightener increased significantly the insecticidal capacity of encapsulated and non-encapsulated viruses, causing a mortality of 100% at that time point, and decreased the median lethal time independently of the incubation temperature and exposure time to radiation. The findings suggested that an encapsulating matrix based on oxidized corn starch might protect the insecticidal capacity of NPV under field conditions.

Distribution of spontaneous gyrA mutations in 97 fluoroquinolone-resistant Helicobacter pylori isolates collected in France.

We determined the prevalence of gyrA mutations conferring fluoroquinolone resistance in 97 Helicobacter pylori isolates collected in France from 2007 to 2010. Ninety-four harbored one or two mutations already found in the quinolone resistance determining region (QRDR) of gyrA (for T87I, n = 23; for N87K, n = 32; for D91N, n = 30; for D91G, n = 7; for D91Y, n = 6), 2 harbored a mutation never previously described (D91H and A88P), and one strain was resistant (ciprofloxacin MIC of 8 mg/liter) without a detected mutation conferring this resistance in gyrA or gyrB genes.

Efficacy and Safety of Doravirine-Based Regimens in Real Life: A Prospective Monocentric French Study.

Doravirine (DOR) efficacy and safety have been evaluated in adult naive or treated patients starting a DOR-based regimen between September 15, 2019, and December 31, 2020. Medical history and examination, laboratory results, and tolerance were assessed during the 48 weeks of follow-up. Among the 77 patients included, virological control (VC) was noticed for 66 patients at baseline. Median age was 51 years, and 62% were men. The most common reason for initiating a DOR-based therapy was toxicity (44; 67%) and, especially, weight gain. A virological suppression (VS) was maintained in 55 (83%) patients of the VC group and noticed in 9 (82%) of the non-VC patients at week 48, by intention-to-treat analysis. On treatment analysis, 98% and 100% patients achieved VS in the VC and non-VC groups, respectively. The renal and metabolic tolerance were good. DOR-based regimens appear to be a safe and relevant strategy to circumvent drug interactions and drugs with a poor metabolic tolerance profile.

Antiviral Effect of hBD-3 and LL-37 during Human Primary Keratinocyte Infection with West Nile Virus.

West Nile virus (WNV) is an emerging flavivirus transmitted through mosquito bites and responsible for a wide range of clinical manifestations. Following their inoculation within the skin, flaviviruses replicate in keratinocytes of the epidermis, inducing an innate immune response including the production of antimicrobial peptides (AMPs). Among them, the cathelicidin LL-37 and the human beta-defensin (hBD)-3 are known for their antimicrobial and immunomodulatory properties. We assessed their role during WNV infection of human primary keratinocytes. LL-37 reduced the viral load in the supernatant of infected keratinocytes and of the titer of a viral inoculum incubated in the presence of the peptide, suggesting a direct antiviral effect of this AMP. Conversely, WNV replication was not inhibited by hBD-3. The two peptides then demonstrated immunomodulatory properties whether in the context of keratinocyte stimulation by poly(I:C) or infection by WNV, but not alone. This study demonstrates the immunostimulatory properties of these two skin AMPs at the initial site of WNV replication and the ability of LL-37 to directly inactivate West Nile viral infectious particles. The results provide new information on the multiple functions of these two peptides and underline the potential of AMPs as new antiviral strategies in the fight against flaviviral infections.

Pooling Rectal, Pharyngeal, and Urine Samples to Detect Neisseria gonorrhoeae, Chlamydia trachomatis, and Mycoplasma genitalium Using Multiplex Polymerase Chain Reaction Is as Effective as Single-Site Testing for Men Who Have Sex With Men.

Background: Screening for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) at pharyngeal, urogenital, and anorectal sites is recommended for men who have sex with men (MSM). Pooling samples is a promising technique, but no data are available when pooled screening also includes Mycoplasma genitalium (MG). The main objective of this study was to examine the sensitivity of pooled samples for detecting CT, NG, and MG in MSM using nucleic acid amplification versus single-site testing. Methods: In this multicenter study, MSM with a positive result for CT, NG, or MG were recalled to the clinic for treatment and were asked to participate in this study. Separate samples were sent to a central virological department that proceeded to form the pooled samples. Testing was performed using the multiplex real-time polymerase chain reaction Allplex STI Essential Assay (Seegene, Seoul, Korea), which can simultaneously detect 7 pathogens. Results: A total of 130 MSM with at least 1 positive test for CT, NG, or MG were included. A total of 25.4% had a coinfection. The sensitivities of pooled-sample testing were 94.8% for CT, 97.0% for NG, and 92.3% for MG. Pooling failed to detect 8 infections, but pooled-sample analysis missed detecting only samples with a low bacterial load (cycle threshold >35). Conclusions: Pooling samples from MSM to detect CT, NG, and MG is as sensitive as individual-site testing for these 3 pathogens using the Allplex assay. Missed infections with a very low bacterial load could have a low impact on further transmission. Clinical Trials Registration. NCT03568695.

Molecular evidence of cryptic speciation, historical range expansion, and recent intraspecific hybridization in the Neotropical seasonal forest tree Cedrela fissilis (Meliaceae).

Molecular phylogeography can lead to a better understanding of the interaction between past climate events, large-scale vegetation shifts, and the evolutionary history of Neotropical seasonal forests. The endangered timber tree species Cedrela fissilis is associated with seasonal forests and occurs throughout South America. We sampled C. fissilis from 56 sites across the species' range in Brazil and Bolivia and obtained sequence data for nuclear and chloroplast DNA. Most specimens (149 out of 169) exhibited intraindividual polymorphism for the nuclear internal transcribed spacer (ITS). Cloning and an array of complementary sequence analyses indicated that the multiple copies of ITS were functional paralogs--concerted evolution in C. fissilis appeared to be incomplete. Independent Bayesian analyses using either ITS or cpDNA data revealed two separate phylogenetic lineages within C. fissilis that corresponded to populations located in separate geographic regions. The divergence occurred in the Early Pliocene and Late Miocene. We argue that climate-mediated events triggered dispersal events and split ancestral populations into at least two large refugial areas of seasonal forest that were located to the east and west of the present day Cerrado. Upon recent climate amelioration, formerly isolated lineages reconnected and intraspecific hybridization gave rise to intraindividual polymorphism and incomplete concerted evolution in C. fissilis.

The Antiviral Activities of Poly-ADP-Ribose Polymerases.

The poly-adenosine diphosphate (ADP)-ribose polymerases (PARPs) are responsible for ADP-ribosylation, a reversible post-translational modification involved in many cellular processes including DNA damage repair, chromatin remodeling, regulation of translation and cell death. In addition to these physiological functions, recent studies have highlighted the role of PARPs in host defenses against viruses, either by direct antiviral activity, targeting certain steps of virus replication cycle, or indirect antiviral activity, via modulation of the innate immune response. This review focuses on the antiviral activity of PARPs, as well as strategies developed by viruses to escape their action.

Characterisation of Antiviral Activity of Cathelicidins from Naked Mole Rat and Python bivittatus on Human Herpes Simplex Virus 1.

Hg-CATH and Pb-CATH4 are cathelicidins from Heterocephalus glaber and Python bivittatus that have been previously identified as potent antibacterial peptides. However, their antiviral properties were not previously investigated. In this study, their activity against the herpes simplex virus (HSV)-1 was evaluated during primary human keratinocyte infection. Both of them significantly reduced HSV-1 DNA replication and production of infectious viral particles in keratinocytes at noncytotoxic concentrations, with the stronger activity of Pb-CATH4. These peptides did not show direct virucidal activity and did not exhibit significant immunomodulatory properties, except for Pb-CATH4, which exerted a moderate proinflammatory action. All in all, our results suggest that Hg-CATH and Pb-CATH4 could be potent candidates for the development of new therapies against HSV-1.