Search Results (406)

Fatty acid-binding proteins (FABPs) are a family of intracellular lipid chaperones that transport fatty acids and other hydrophobic molecules, playing essential roles in cellular lipid metabolism, signaling, and brain function. Within the central nervous system, FABP3, FABP5, and FABP7 facilitate the trafficking of long-chain polyunsaturated fatty acids and endocannabinoids, thereby modulating key regulatory pathways including the endocannabinoid system (ECS), peroxisome proliferator-activated receptor (PPAR) signaling, and dopaminergic neurotransmission. Peripherally, FABP1 and FABP4 contribute to hepatic drug metabolism, kidney excretion, and inflammatory processes in both tissues, with implications for the pharmacokinetics of substances of abuse. This narrative review synthesizes the current literature on FABPs and their involvement in substance use and addiction-related behaviors. Evidence from transgenic knockout models, pharmacological inhibition studies, and adeno-associated virus vector approaches demonstrates that manipulation of FABP subtypes can alter reward-related behaviors across multiple substances, including THC, ethanol, nicotine, and cocaine. Reduction or knockout of FABP7 alters THC metabolite levels in a sex-dependent manner. FABP3 shows involvement with dopamine receptor expression; however, interaction between FABP3 modulation and specific substances has sparsely been investigated. FABP5 has vastly diverging interactions with addictive behavior and appears to be substance dependent, as downregulation reduces cocaine self-administration, but knockout enhances nicotine conditioned place preference (CPP) and increases brain uptake of THC. Combined deletion of FABP5 and 7 additionally reduces cocaine CPP and reinstatement, while showing promising decreases in ethanol consumption paradigms. FABPs may be a potential therapeutic target for treating substance use disorders and underlying reward deficiency mechanisms underlying addiction and further research is required to elucidate specific mechanistic effects and eliminate potential adverse consequences of chronic FABP modulation. Full article

Autophagy is a conserved cellular degradation pathway that plays important roles in insect–virus interactions. In the MED cryptic species of Bemisia tabaci, cotton leaf curl Multan virus (CLCuMuV) can persist upon acquisition, yet this vector fails to transmit the virus. However, whether autophagy contributes to this antiviral response in MED whiteflies remains unknown. In this study, we show that CLCuMuV acquisition activates autophagy in MED whiteflies, as evidenced by increased LC3-I to LC3-II conversion, enhanced LC3-positive puncta formation in the gut, and dynamic transcriptional regulation of multiple autophagy-related genes. Functional investigations using RNAi-mediated silencing of Atg3 and Atg9, two essential autophagy genes, revealed that their knockdown elevated viral DNA accumulation by 1.4-fold at 48 h post-acquisition. Consistently, pharmacological blockade of autophagic flux with bafilomycin A1 led to a 1.0-, 2.2-, and 1.0-fold increase in viral loads across 24, 48, and 72 h post-acquisition, respectively, whereas treatment with rapamycin, an autophagy inducer, decreased viral DNA accumulation by 46.4% and 33.3% relative to control levels at 24 and 48 h post-acquisition, respectively. Together, these loss- and gain-of-function experiments demonstrate that autophagy functions as a host restriction mechanism that limits CLCuMuV persistence in MED whiteflies, providing molecular insights into the immune competence of this non-vector species. Full article

RNA-dependent RNA polymerases (RdRPs) are essential enzymes involved in RNA virus replication and eukaryotic RNA silencing. They are generally absent in vertebrates but present in some invertebrate lineages, such as nematodes and certain arthropods. Brevipalpus yothersi is a phytophagous mite of agricultural relevance due to its role as a vector of plant-infecting viruses. We have identified two RdRPs on the genome of this mite species that, unexpectedly, are not of eukaryotic origin. Phylogenetic reconstruction and comparisons of 3D protein structures revealed similarity with viral RdRPs of the Partitiviridae family. Both RdRPs retain conserved catalytic motifs at the protein sequence level, and expression was confirmed by RNAseq and qPCR across mite developmental stages, with a peak during the nymphal stage. K-mer profiles showed similarity with mite endogenous genes, suggesting gene amelioration after the integration, or being derived from a viral donor already adapted to the mite. Our study also identified orthologs in other Brevipalpus species, but not in other Acari relatives, supporting that the horizontal gene transfer event is circumscribed to the Brevipalpus genus. These findings highlight an intriguing case of viral gene domestication in arthropods that might influence their developmental biology and the host–virus interaction. Full article

In this paper, we investigate a reaction–diffusion system governing the vector-borne and sexual transmission dynamics of the Zika virus between host (human) and vector (mosquito) populations. Adopting the compartmental methodology, the human population is divided into susceptible, exposed, infected, and recovered classes, while the mosquito population is partitioned into susceptible, exposed, and infected compartments. We consider several assumptions for disease transmission; in particular, we consider the transmission from infected to susceptible humans to occur through sexual interaction. The first contribution of this work lies in incorporating spatial displacement for both populations, modeled via Fick’s law with a spatially varying diffusion coefficient to capture environmental heterogeneity. To reflect an epidemiologically closed domain, homogeneous Neumann (zero-flux) boundary conditions are imposed, ensuring total population mass conservation principles. As a second advancement, we establish rigorous mathematical results regarding the well-posedness, boundedness, and positivity of solutions to the resulting reaction–diffusion system. The third innovation of the paper is the fact that an unconditional convergent and biologically consistent finite difference numerical scheme is developed to resolve the coupled non-linear governing equations. Finally, we provide a comprehensive set of numerical simulations focused on the parameter sensitivity. Full article

Aortic dissection (AD) is a severe vascular condition marked by abrupt onset, rapid progression, and heightened mortality rates. Vascular smooth muscle cells (VSMCs), the predominant cellular component of the arterial media, are essential for maintaining the structural integrity and functionality of blood vessels. Recent studies have associated Cysteine-rich protein 2 (CSRP2) with the advancement of several vascular diseases. The involvement of CSRP2 in AD progression is unclear. Aortic tissues were collected from patients for RNA sequencing and histological analysis. A mouse model of AD was created using β-aminopropionitrile monofumarate (BAPN), while VSMC phenotypic switching was induced by platelet-derived growth factor BB (PDGF-BB). Adeno-associated virus vector was used to overexpress CSRP2 in aorta. A variety of histopathological assays and biochemical analyses were applied to determine gene and protein expression patterns as well as uncover underlying molecular mechanisms. CSRP2 was significantly downregulated in both human and murine AD, and CSRP2 gene overexpression dramatically reduced BAPN-induced AD incidence and prevented animal mortality. CSRP2 could preserve a contractile VSMC phenotype, even though under PDGF-BB stimulation. Mechanistically, our findings reveal that CSRP2 directly interacts with p130 Crk-associated substrate (p130Cas; also known as BCAR1) and reduces its phosphorylation, which in turn inhibits the activation of extracellular signal-regulated kinase (ERK) signaling pathways, thereby preventing VSMC phenotypic switching induced by PDGF-BB. Our findings identify CSRP2 as a novel regulator of VSMC phenotypic modulation and a significant modulator of AD development, suggesting its potential as a target for early intervention for AD. Full article

West Nile virus (WNV) is a mosquito-borne pathogen of escalating epidemiological importance and a growing global health concern, driven by the climate-associated expansion of its Culex mosquito vectors. Although WNV is an extensively studied flavivirus, most host–pathogen interaction studies focus on static and structural aspects rather than dynamic and functional ones. Delineating phosphorylation-mediated interactions between WNV proteins and human kinases bridges a critical gap by providing important insight into the molecular mechanisms underlying infection. In this study, we investigated potential phosphorylation-mediated interactions between WNV proteins and human kinases using an integrative computational framework combining motif prediction, phosphoproteomic data analysis and structural docking. Key interactions were predicted between viral proteins and regulatory kinases within the AKT-ERK pathway and the AMPK-mediated autophagy, including major network kinases such as RAF1, IKBKB, and ULK1. In addition, experimentally validated phosphorylation sites in viral proteins were found to be associated with multiple candidate host kinases, including MAP2K7 and MAP2K9, suggesting complex regulatory networks. Integration with phosphoproteomic datasets supported the relevance of multiple predicted kinases, including those associated with antiviral responses and translational regulation. Protein–protein docking demonstrated stable, energetically favorable interactions between selected host kinases and viral proteins, particularly the viral polymerase (NS5), helicase (NS3), and NS1. The findings of this study establish a framework for future research on the development of host-directed antiviral strategies. Full article

Assessing mosquito vector competence for emerging arboviruses, including the underlying determinants of infection, is a foundational line of investigation towards understanding arbovirus transmission dynamics and vector–virus interactions. We developed a novel quantitative immune gene array that measures the relative expression of 22 immune genes with functional representation across five major immune pathways using quantitative reverse-transcriptase polymerase chain reaction. Homologous primers were developed for Culex tarsalis, Cx. quinquefasciatus, and Ae. aegypti mosquitoes. As an initial pilot test for this array, Cx. tarsalis and Ae. aegypti mosquitoes were orally challenged with Rift Valley fever virus (RVFV) MP12 strain. Midguts, legs/wings, and salivary glands were harvested at 3 and 7 days post-challenge. Differential gene expression was measured against Rpl32 as a housekeeping gene. This assay was sensitive enough to generate results for single mosquito midgut and salivary gland tissues, providing an initial snapshot of the types of gene expression patterns that can be observed for two mosquito species infected with MP12. This new tool will be broadly applicable for assessing mosquito immune profiles for arbovirus infection across major immune genes in five key pathways, as well as generating comparable results across mosquito and arbovirus systems. Full article

The Oropouche virus (OROV), an orthobunyavirus primarily transmitted by the biting midge Culicoides paraensis, is the causative agent of Oropouche fever, a re-emerging arboviral disease associated with significant morbidity in Central and South America. The increasing frequency of outbreaks, including cases of sustained transmission in non-endemic regions and reports of vertical transmission, highlights the growing public health concern posed by OROV. Currently, there are no specific antiviral therapies or licensed vaccines available, underscoring the urgent need for effective therapeutic and preventive strategies. Recent advances in antiviral research have identified promising candidates, including repurposed drugs and bioactive compounds that target key stages of the viral replication cycle. In parallel, vaccine development has progressed through modern platforms, including viral vector-based and nucleic-acid-based technologies, enabling rapid responses to emerging outbreaks. However, major challenges remain, particularly due to the limited understanding of OROV pathogenesis, virus–host interactions, and the correlates of protective immunity. Furthermore, the ongoing evolution of OROV, including the genetic diversity and potential genomic rearrangements observed among circulating strains, represents an additional challenge that may influence viral characteristics and potentially affect the long-term efficacy of antiviral interventions and vaccine-induced protection. This review summarizes recent advances in the discovery of antiviral candidates and the development of vaccine approaches against OROV, both of which are essential for reducing the impact of OROV infections and strengthening preparedness for future outbreaks. Full article

Adeno-associated virus (AAV) is a small ssDNA satellite virus that receives wide attention due to its popularity as a safe and effective gene therapy vector. The AAV cell entry receptor (AAVR) for most serotypes is a glycoprotein containing five polycystic kidney disease (PKD) domains with which AAV interacts. AAV serotypes can be classified into three groups: those that interact primarily with PKD1, those whose interactions with PKD2 are stronger, and AAV4-like serotypes whose transduction is AAVR-independent. A phylogenetic analysis of AAVR and paralog KIAA0319 revealed AAVR amino acid variability in the region of PKD1 that is bound by AAV. We hypothesized that the substitution, in all cat-like animals, of a glutamate at a site that is an arginine (R353) in human AAVR may interfere with the binding of clade H AAVs that interact exclusively with PKD1. Analysis of PKD1 mutations, including ELISA, shows that an R353E substitution of glutamate for arginine affects the binding of the clade H AAVs that interact primarily with PKD1. Full article

Background/Objectives: Emerging viral zoonoses represent a growing threat to global public health, with most newly emerging infectious diseases originating from animal reservoirs. Recent outbreaks of monkeypox, Ebola virus disease, Marburg virus disease, Rift Valley fever, and avian influenza highlight the capacity of zoonotic viruses to cross species barriers, spread internationally, and generate substantial health, social, and economic consequences. This review examines the ecological, epidemiological, and biological determinants of viral zoonotic emergence and transmission, with particular emphasis on vaccination and outbreak prevention strategies. Methods: A structured narrative review was conducted using a predefined literature search strategy across major scientific databases. Peer-reviewed epidemiological, clinical, and public health publications published between January 2000 and February 2026 were screened and selected according to predefined relevance criteria. Results: The emergence of viral zoonoses is driven by complex interactions among animal reservoirs, environmental and climatic changes, human behavior, and viral adaptation. Although transmission pathways and clinical outcomes differ among pathogens, common determinants of spillover and outbreak amplification were identified. Current evidence supports the importance of integrated surveillance, genomic monitoring, vaccination strategies, and community engagement as key components of preparedness and response. Emerging preventive approaches targeting pathogen transmission, including transmission-blocking strategies and vector-associated microbiota interventions, may provide additional opportunities for disease control. Conclusions: Strengthening preparedness for emerging viral zoonoses requires coordinated One Health approaches integrating human, animal, and environmental health. Future priorities include the development of next-generation vaccines, expansion of digital and genomic surveillance systems, improved equitable access to vaccines, and innovative interventions aimed at reducing zoonotic spillover and interrupting pathogen transmission. Full article

Dengue Virus (DENV) circulates as four antigenically distinct serotypes whose dominance fluctuates over time in many endemic regions, a phenomenon known as serotype shift that is frequently associated with large outbreaks and increased disease severity. This review, through a synthesis of epidemiological, virological, immunological, entomological, and environmental evidence, observes that serotype shift likely arises from the interaction of multiple determinants rather than solely from viral evolution, with population immunity playing a central role. The accumulation of serotype-specific herd immunity, together with short-lived cross-protection and Antibody-Dependent Enhancement (ADE), reshapes population susceptibility and creates ecological space for heterologous serotypes with higher transmission potential. The synthesis of global dengue studies indicates that these immune dynamics interact with viral genetic diversity, vector competence, climate variability, and human factors such as demography, socioeconomic status, population density and mobility to drive cyclical and sometimes abrupt changes in serotype dominance. Notably, the review indicates that serotype changes often precede or coincide with more clinical severity and patterns of outbreaks, with direct implications for the process of forecasting outbreaks, vaccine performance, and preparedness to respond with appropriate health measures. On the whole, this review confirms the opinion that the change of dengue serotype occurrence becomes a consequence of interconnected biological and ecological processes involved in the transmission of dengue serotype shifts in hyperendemic areas. Full article

O’nyong-nyong virus (ONNV) is a mosquito-borne alphavirus responsible for large-scale epidemics in sub-Saharan Africa. As the closest evolutionary relative of Chikungunya virus (CHIKV), ONNV shares substantial genetic similarity and overlapping clinical manifestations with CHIKV. Mechanistic understanding of ONNV infection has therefore largely been extrapolated from CHIKV rather than directly established. However, ONNV exhibits distinct biological features, including predominant transmission by Anopheles mosquitoes and a clinical presentation characterized by prominent lymphadenopathy with limited acute joint edema. These distinctions underscore the need for an integrated synthesis of experimentally validated determinants of ONNV infection. In this review, we summarize current evidence on molecular and immunological factors regulating ONNV infection in mammalian hosts and mosquito vectors. We first discuss species-specific viral clearance, host dependency factors, intrinsic antiviral restriction mechanisms, protective innate immunity, inflammatory pathology, and mechanism-informed therapeutic strategies in mammalian hosts. We then examine stage-specific immune regulation in Anopheles mosquitoes, emphasizing mechanisms that constrain viral replication while permitting persistent infection and transmission. Finally, we discuss nsP3-dependent vector specificity and the potential contribution of alternative mosquito species to ONNV ecology. Together, this review provides an integrated framework for understanding how host factors, immune responses, and vector-specific adaptations shape ONNV infection, pathogenesis, and transmission. Full article

The mosquito-associated virome may modulate host biology and influence vector competence, highlighting the importance of understanding its composition. Here, a metagenomic analysis was conducted to characterize the virome of the sea-rock pool mosquito Aedes mariae across sexes and developmental stages, together with water from its sea-rock pool breeding site in San Felice Circeo (Italy). A total of 51 viral taxa were identified, including viruses associated with bacteria and archaea (39%), plants, algae, fungi, and protists (35%), vertebrates (8%), and invertebrates (18%), including insect-specific viruses such as Mesoniviridae, Baculoviridae, Nudiviridae, Iridoviridae and Totiviridae. Twenty-five percent of the taxa were shared across samples, suggesting acquisition from breeding-site water and persistence across stages during development. Interestingly, the need for host genome filtering highlights the potential sequence similarity between viral and mosquito genomes, which may reflect the presence of endogenous viral elements or historical virus–host interactions. These findings represent the first characterization of the virome of Aedes mariae and highlight the role of aquatic breeding sites in shaping mosquito virome. Finally, we argue the importance of adequate sequencing depth and host genome filtering to capture the diversity of the mosquito virome. Full article

The southern rice black-streaked dwarf virus (SRBSDV) is transmitted by the white-backed planthopper (WBPH), Sogatella furcifera, but not by the co-occurring brown planthopper (BPH), Nilaparvata lugens. Understanding the influence of virus infection of host plants on the performance of close-related vector and non-vector species is an interesting topic for exploring virus–plant–herbivore interactions. This study investigates how SRBSDV infection of rice plants affects the performance of WBPH and BPH and the plant defense responses. Differential performance of the two planthopper species was observed. On infected plants, WBPH displayed prolonged male nymphal development, increased adult longevity, enhanced feeding, and reduced fecundity, which contrasts the reduced nymph survival and fecundity in BPH. SRBSDV infection triggered an increase in salicylic acid (SA) levels and upregulated the expression of SA-related genes (ICS1 and NPR1) in response to WBPH feeding, but not to BPH feeding. These results show that SRBSDV reshapes the host plant defense in a manner that alters key vector traits favoring virus transmission while impairing the fitness of a competing non-vector, which advances current understanding of virus–plant–herbivore interaction. Full article

Reliable quality control of adeno-associated virus (AAV) vectors remains a major bottleneck in gene therapy manufacturing, particularly for resolving subtle differences in genome loading and conformation at the single-particle level. Existing approaches often struggle to distinguish AAV populations with similar mass and charge, such as capsids carrying self-complementary versus single-stranded DNA. Here, we introduce an AC plasmonic nanopore sensing framework for AAV9 characterization. Individual AAV capsids were optically trapped within a plasmonic double-nanohole nanopore and interrogated using multi-frequency AC pulse trains spanning 500 Hz to 100 kHz. To enhance sensitivity to localized particle–field interactions, a nanofabricated Ag/AgCl ring electrode was integrated concentrically with the plasmonic nanopore. Relative to a conventional wire electrode, the ring electrode produced broader and more robust analyte-dependent differences across multiple frequency-dependent parameters, enabling reliable discrimination of empty capsids (AAV_empty) and genome-loaded capsids carrying either self-complementary (AAV_scDNA) or single-stranded DNA (AAV_ssDNA), despite their near-identical genome mass. Concentration titration experiments further demonstrated that the extracted multivariate AC features remained largely concentration-independent over the tested range. Together, these results demonstrate that ring-electrode-enabled AC plasmonic nanopore sensing provides a multidimensional framework for resolving closely related AAV populations and advances plasmonic nanopores toward practical single-particle quality control of gene therapy vectors. Full article