Search Results (281)

The ability of a virus to be propagated within a host cell is dependent on a multitude of dynamic virus–host interactions. Live-cell imaging is an invaluable approach in the study of virus replication cycles and virus–host interactions as it can allow for the direct visualisation of key events and interactions in real time. These details can provide unique insights into many aspects of viral infections including the cellular pathways that are exploited by viruses, the evasion of host immune defences, and viral pathogenesis. This review summarises the live-cell fluorescence imaging approaches that have been developed and applied to study Flaviviridae virus family members that are responsible for significant public health burdens and outbreaks which, in many instances, are increasing in frequency and severity. We discuss how these approaches have expanded our understanding of fundamental stages of viral replication cycles by enabling the direct visualisation of the localisation, trafficking, and interactions of virus particles, proteins, and genomes at distinct stages. The strategies that can be employed to enhance the biological relevance of live-cell fluorescence imaging acquisitions are discussed, along with how live-cell imaging approaches can be further developed to increase resolution, enable multi-colour imaging, and support the long-term visualisation of multiple stages of a viral replication cycle. Full article

Arthropod-borne viruses (arboviruses) represent a growing concern for global public and veterinary health, with cases reported across all continents. This review presents a broad overview of the geographic distribution of arboviruses transmitted by insect vectors, emphasizing the importance of early viral detection as a cornerstone of surveillance and outbreak preparedness. Special attention is given to the phenomenon of zoonotic spillover, where viruses maintained in natural transmission cycles often involving wildlife reservoirs and arthropod vectors cross into human populations, triggering emergent or re-emergent outbreaks. This article discusses key arboviral families of medical and veterinary significance, including Togaviridae, Flaviviridae, Nairoviridae, Phenuiviridae, Peribunyaviridae, and Orthomyxoviridae, highlighting their molecular and structural characteristics. These features are essential for guiding the development and implementation of specific and sensitive detection strategies. In addition, this work provides a comparative analysis of diverse laboratory methodologies for viral detection in vectors. From serological assays and viral isolation to advanced molecular tools and next-generation sequencing, we explore their principles, practical applications, and context-dependent advantages and limitations. By compiling this information, we aim to support researchers and public health professionals in selecting the most appropriate tools for vector surveillance, ultimately contributing to improved response strategies in the face of arboviral threats. Full article

Bovine viral diarrhea (BVD) is caused by bovine viral diarrhea virus (BVDV), a member of the genus Pestivirus and in the family Flaviviridae. According to some studies, the disease incurs USD 1.5–2.5 billion per year and USD 0.50 to USD 687.80 per cow loss in beef and dairy farms, respectively. Using vaccines is among the strategies to prevent the disease. However, complete protection requires vaccines that target both the humoral and cellular immune responses of the adaptive immune system. A comprehensive literature review was made to provide insights into the interaction of BVDV with host immunity, vaccine applications, and the limitation of the currently available vaccines, as well as explore strategies used to advance the vaccines. BVDV causes immunosuppression by interfering with the innate and adaptive immune systems in a manner that is species and biotype-dependent. Interferon production, apoptosis, neutrophil activity, and antigen-processing and presenting cells are significantly affected during the viral infection. Despite maternal antibodies (MatAbs) being crucial to protect calves from early-age infection, a higher level of MatAbs are counterproductive during the immunization of calves. There are numerous inactivated or modified BVDV vaccines, most of which are made of cytopathic BVDV 1 and 2 and the BVDV 1a subgenotypes. Furthermore, subunit, marker, DNA and mRNA vaccines are made predominantly from E2, E^rns, and NS₃ proteins of the virus in combination with modern adjuvants, although the vaccines have not yet been licensed for use and are in the experimental stage. The existing BVDV vaccines target the humoral immune system, which never gives the full picture of protection without the involvement of the cell-mediated immune system. Several limitations were associated with conventional and next-generation vaccines that reduce BVDV vaccine efficiency. In general, providing complete protection against BVDV is very complex, which requires a multi-pronged approach to study factors affecting vaccine efficacy and strategies needed to improve vaccine efficacy and safety. Full article

Flaviviruses are arthropod-borne RNA viruses that can cause a wide range of human diseases, from mild symptoms to severe illness with multiorgan failure and death. Effective prevention of these diseases relies on identifying reliable vaccine targets, typically measured by correlates of protection (CoPs), which help indicate host immunity after vaccination. Current vaccines primarily focus on neutralizing antibodies (nAbs) against the viral envelope E protein, though emerging evidence suggests other potential targets may also be effective in disease prevention. Additionally, there is growing evidence of cross-protection between different flaviviruses when immunity to one virus is achieved, although this can be limited by antibody-dependent enhancement. This review examines the current understanding of flavivirus immunity, CoPs, and the potential for cross-protection in the context of existing vaccine strategies. Full article

Background: Dengue virus (DENV) is the fatal pathogenic arthropod-borne virus (arboviruses) that belongs to the Flaviviridae family, which transmits to humans through mosquito bites from infected Aedes aegypti and Aedes albopictus mosquitoes or maternal-fetal transmission. Despite antigenic differences, the four serotypes of DENV (DENV-1 to DENV-4) share 65–78% of their genome. Non-structural (NS) proteins amongst serotypes show analogous functions. Among NS proteins, NS3 and NS5 are frequently used as targets for antiviral drugs due to their multifunctional roles. Methods: To identify potential inhibitors of DENV, we created a phytochemical library of 898 compounds derived from 17 medicinal plants recognized for their medicinal and antiviral properties. The phytochemicals library has been docked against the target proteins. Phytochemicals with a docking score greater than −8.0 kcal/mol were selected for further evaluation using a machine learning approach. Further, molecular dynamics (MD) simulations were conducted to evaluate the root mean square deviation, root mean square fluctuation, solvent-accessible surface area, radius of gyration, and hydrogen bond count of the compounds. Results: From the docking results, Silibinin, Rubiadin, and Ellagic acid showed binding affinities of −8.5, −8.3, and −8.2 kcal/mol, respectively, for NS3, and NSC 640467, Bisandrographolide A, and Andrographidin A showed binding affinities of −9.3, −10.1, and −9.3 kcal/mol, respectively, for NS5 target proteins. These compounds exhibited strong interactions with target proteins. MD simulation results confirmed the stable formation of protein–ligand complexes. Further, absorption, distribution, metabolism, excretion, and toxicity (ADMET) and bioactivity predictions confirmed their pharmacological safety. Conclusions: Despite global public health concerns, DENV still lacks specific drug treatments. Our identified new drug candidates might help for developing effective antiviral inhibitors against the DENV. However, further confirmation is needed through in vivo and in vitro research. Full article

West Nile virus (WNV) is an important zoonotic pathogen belonging to the Flaviviridae family, which is endemic in some areas and emerging in others. WNV is transmitted by blood-sucking mosquitoes of the genus Culicoides, Aedes, and Anopheles, and the infection can cause different clinical symptoms. The most common and benign illness in humans is West Nile fever (WNF), but a lethal neurological disease (WNND), related to the neuro-invasiveness of WNV lineage 2, represents the highest health risk of WNV infection. The neuro-clinical form is recognized in mammals (land and cetaceans), particularly in humans (elderly or immunosuppressed) and in horses, avian species, and wildlife animals ranging free or in a zoological setting. This review highlights the most relevant data regarding epidemiology, virology, pathogenesis and immunity, clinical signs and differential diagnosis, pathology and imaging, histopathology and gross pathology, economic impact, influence of climate change, and surveillance of WNV. Climate change has favored the wide spread of WNV in many areas of the globe and consequent One-Health and Eco-Health emergencies, influencing the health of human beings, animals, and ecosystems. Full article

Infectious precocity virus (IPV) poses a significant economic threat to the aquaculture industry by causing sexual precocity and slow growth in Macrobrachium rosenbergii. In this study, we conducted an in-depth investigation into the genetic evolution of IPV from 2011 to 2024 by collecting 31 IPV variants through epidemiological surveys and public databases, including 29 variants with complete genomic sequences. The phylogenetic analysis revealed that these complete genomic sequences clustered into two distinct phylogenetic clades as follows: the Southeast Asian clade and the Chinese clade. Nucleotide and protein variation analyses demonstrated a high degree of similarity, with nucleotide identity ranging from 98.5% to 100% and protein identity from 99.4% to 100%. Further analysis of protein variations within the putative coding region identified two distinct variation patterns. The average dN/dS ratio of 0.12 highlights the strong purifying selection acting on IPV, particularly on structural proteins. In conclusion, this study significantly expands the genomic database of IPV and provides valuable insights into its genetic evolution. These findings offer critical scientific evidence to enhance detection protocols and support sustainable M. rosenbergii aquaculture practices. Full article

Zika virus (ZIKV) is a mosquito-borne flavivirus of the family Flaviviridae. The association between ZIKV and microcephaly was first described in Brazil in 2015. The risk of vertical transmission occurs in pregnant women with or without symptoms, and the risk of malformation appears to be worse when infection occurs in the first and second trimesters of pregnancy. The rate of vertical transmission varies from 26 to 65%, and not all fetuses develop malformations. The incidence of malformations resulting from transmission is uncertain, ranging from 6–8% in the US to 40% in Brazil. Congenital ZIKV syndrome is a set of clinical manifestations that can affect the fetus of a mother infected with ZIKV. The manifestations are broad and nonspecific, including microcephaly, subcortical calcifications, ocular changes, congenital contractures, early hypertension, and pyramidal and extrapyramidal signs. Other findings such as growth restriction and fetal miscarriage/death may also occur. Our aim in this article is to review the literature on mosquito transmission, clinical presentation, serologic diagnosis, intrauterine transmission, pre- and postnatal imaging diagnostic findings, and short- and long-term follow-up. Full article

Omsk hemorrhagic fever virus (OHFV) is the etiological agent of a poorly studied acute viral disease, causing several epidemic waves observed in the western Siberia regions of Omsk, Kurgan, Novosibirsk, and Tyumen. OHFV is a flavivirus and shares structural and morphological features with tick-borne encephalitis (TBE) complex viruses. The disease’s symptoms show high variability, from flu-like symptoms, hyperesthesia, and petechial rush in the upper body to high fever and hemorrhagic manifestations, with a fatality rate of about 1%. The real number of OHFV-infected people is still unknown due to the difficulties in diagnosis and the presence of asymptomatic patients that lead to an underestimation of the total cases. Little is known about the viral infection dynamics at the molecular and cellular levels, the viral involvement in immune escape, cellular pathways alteration, or metabolic influence. It is noteworthy that no clinical trials have currently been performed for effective and specific drug treatments. In this review, we will give an overview of OHFV interactions with humans and animals, diagnostic tools, and drug treatments. We aim to highlight the importance of a frequently undiagnosed or misdiagnosed viral infection that might also even cause severe clinical manifestations such as meningitis and hemorrhage, in order to point out the need to develop new research studies, new diagnostic tools, and new treatments for OHFV. Full article

Orthoflavivirus, a genus encompassing arthropod-borne, positive-sense, single-stranded RNA viruses in the Flaviviridae family, represents clinically relevant viruses that pose significant threats to human and animal health worldwide. With warming climates and persistent urbanization, arthropod vectors and the viruses they transmit continue to widen their geographic distribution, expanding endemic zones. Flaviviruses such as dengue virus, Zika virus, West Nile virus, and tick-borne encephalitis virus cause debilitating and fatal infections globally. In 2024, the World Health Organization and the Pan American Health Organization declared the current dengue situation a Multi-Country Grade 3 Outbreak, the highest level. FDA-approved treatment options for diseases caused by flaviviruses are limited or non-existent, and vaccines are suboptimal for many flaviviruses. Understanding the molecular characteristics of the flavivirus life cycle, virus-host interactions, and resulting pathogenesis in various cells and model systems is critical for developing effective therapeutic intervention strategies. This review will focus on the virus-host interactions of mosquito- and tick-borne flaviviruses from the virus replication and assembly perspective, emphasizing the interplay between viral non-structural proteins and host pathways that are hijacked for their advantage. Highlighting interaction pathways, including innate immunity, intracellular movement, and membrane modification, emphasizes the need for rigorous and targeted antiviral research and development against these re-emerging viruses. Full article

Bussuquara virus (BSQV) was first discovered in the Brazilian Amazon in 1956. It is an arthropod-borne virus (arbovirus) in the genus Orthoflavivirus, family Flaviviridae. Since its discovery, BSQV has been sporadically detected across the South (Brazil, Columbia, and Argentina) and Central (Panama and Mexico) America and the Caribbean (Grenada), but there is minimal BSQV surveillance due to limited public health awareness and a lack of specific or sensitive diagnostics. BSQV exposure has been reported in a wide range of host and vector species, including humans. Little information is available in the literature and herein we summarize the published historical findings on BSQV and suggest a pathway for future studies to better understand its potential emergence into human populations. Full article

Zika virus (ZIKV), a member of the Flaviviridae family, is primarily transmitted through mosquito bites, but can also spread via sexual contact and from mother to fetus. While often asymptomatic, ZIKV can lead to severe neurological conditions, including microcephaly in fetuses and Guillain–Barré Syndrome in adults. ZIKV can infect placental macrophages and fetal microglia in vivo as well as human monocytes and monocyte-derived macrophages (MDMs) in vitro. Here, we observed that both human monocytes, and MDM particularly, supported ZIKV replication without evident cytopathicity, with virions accumulating in cytoplasmic vacuoles. We also investigated whether the cytokine-induced polarization of MDMs into M1 or M2 cells affected ZIKV replication. The stimulation of MDMs with pro-inflammatory cytokines (interferon-γ and tumor necrosis factor-α) polarized MDMs into M1 cells, significantly reducing ZIKV replication, akin to previous observations with a human immunodeficiency virus type-1 infection. In contrast, M2 polarization, induced by interleukin-4, did not affect ZIKV replication in MDMs. M1 polarization selectively reduced the expression of MERTK, a TAM family putative entry receptor, and increased the expression of several interferon-stimulated genes (ISGs) previously associated with the containment of ZIKV infection; of interest, ZIKV infection transiently boosted the expression of some ISGs in M1-MDMs. These findings suggest a dual mechanism of ZIKV restriction in M1-MDMs and highlight potential antiviral strategies targeting innate immune responses. Full article

Hepatitis C virus (HCV), a member of the Flaviviridae family, is an RNA virus enclosed in an envelope that infects approximately 50 million people worldwide. Despite its significant burden on public health, no vaccine is currently available, and many individuals remain unaware of their infection due to the often asymptomatic nature of the disease. Early detection of HCV is critical for initiating curative treatments, which can prevent long-term complications such as cirrhosis, liver cancer, and decompensated liver disease. However, conventional diagnostic approaches available, such as enzyme immunoassays (EIAs) and polymerase chain reaction (PCR)-based methods, are often costly, time-intensive, and challenging to be implemented in resource-limited settings. This review provides an overview of HCV disease and the structural components of the virus, illustrating how different diagnostic methods target various parts of the viral structure. It examines current diagnostic tests and assays, highlighting their mechanisms, applications, and limitations, which necessitates the development of improved detection methods. Additionally, the paper explores emerging technologies in HCV detection that could offer affordable, accessible, and easy-to-use diagnostic solutions, particularly for deployment in low-resource and point-of-care settings. These advancements have the potential to contribute significantly to achieving the World Health Organization’s (WHO) target of eliminating HCV as a public threat by 2030. Full article

The European subtype of tick-borne encephalitis virus (TBEV-Eur; species Orthoflavivirus encephalitidis, family Flaviviridae) was the only tick-borne flavivirus present in central Europe known to cause neurologic disease in humans and several animal species. Here, we report a tick-borne flavivirus isolated from Alpine chamois (Rupicapra rupicapra rupicapra) with encephalitis and attached ticks, present over a wide area in the Alps. Cases were detected in 2017 in Salzburg, Austria, and 2023 in Lombardy and Piedmont, Italy. The virus strains exhibit 94.8–97.3% nucleotide identities to each other and are more closely related to Louping ill viruses (LIV; Orthoflavivirus loupingi; 90–92% identities) than to TBEV-Eur (less than 88%). The chamois-derived virus strains, tentatively termed “Alpine chamois encephalitis virus”, form a well-supported independent genetic clade with Spanish goat encephalitis virus, clearly separated from other LIV. This supports its designation as a new virus subtype with the proposed shared taxonomic name “Spanish goat and Alpine chamois encephalitis virus subtype” within the species Orthoflavivirus loupingi. The zoonotic potential of this newly identified virus subtype as well as its host range in other animal species including farm animals needs to be further investigated. Full article

The first marine pestivirus, Phocoena pestivirus (PhoPeV), isolated from harbor porpoise, has been recently described. To further characterize this unique pestivirus, its host cell tropism and growth kinetics were determined in different cell lines. In addition, the interaction of PhoPeV with innate immunity in porcine epithelial cells and the role of selected cellular factors involved in the viral entry and RNA replication of PhoPeV were investigated in comparison to closely and distantly related pestiviruses. While Bungowannah pestivirus (BuPV), a unique porcine pestivirus closely related to PhoPeV, exhibits a broad cell tropism, PhoPeV only infects cells from pigs, cattle, sheep, and cats, as has been described for classical swine fever virus (CSFV). Viral titers correlate with the amount of intracellular PhoPeV-specific RNA detected in the tested cell lines. PhoPeV replicates most efficiently in the porcine kidney cell line SK6. Pestiviruses generally counteract the cellular innate immune response by degradation of interferon regulatory factor 3 (IRF3) mediated by the viral N-terminal protease (N^pro). No degradation of IRF3 and an increased expression of the type 1 interferon-stimulated antiviral protein Mx1 was observed in porcine cells infected with PhoPeV whose genome lacks the N^pro encoding region. Infection of a CD46-deficient porcine cell line suggested that CD46, which is implicated in the viral entry of several pestiviruses, is not a major factor for the viral entry of PhoPeV. Moreover, the results of this study confirmed that the cellular factor DNAJC14 plays a crucial role in viral RNA replication of non-cytopathic pestiviruses, including PhoPeV. Full article