Search Results (17)

Vesicular stomatitis virus (VSV) causes clinical disease in livestock that mimics Foot-and-Mouth Disease, necessitating its status as a reportable pathogen to the World Organization for Animal Health. Given the importance of accurate classification for epidemiological surveillance, this study aims to update VSV taxonomic organization using whole-genome sequence criteria to better monitor disease dynamics. Using phylogenetic analysis and the Species Demarcation Tool (SDT), we analyzed pairwise identity across publicly available sequences, constructing a rooted maximum likelihood tree to cluster strains based on robust genetic identity scores. The results demonstrate that nucleotide divergences exceeding 30% define distinct species within the Vesiculovirus genus. Within a species, divergences between 10% and 30% successfully delineate genotypes, while differences between 6% and 10% identify specific subtypes. These quantitative benchmarks provide a precise framework for viral classification, significantly enhancing genomic surveillance and the ability to track the evolution and transmission of VSV genotypes and subtypes across diverse geographic regions. Full article

Oncolytic viruses (OVs) exploit key hallmarks of cancer to selectively replicate in malignant cells, leading to tumor cell lysis, modulation of the tumor microenvironment, and induction of antitumor immunity. These viral platforms have been engineered to enhance tumor specificity, intratumoral spread, and immunotherapeutic efficacy. Among them, rhabdoviruses, particularly vesiculoviruses, have emerged as promising candidates due to their rapid replication, high titers, and amenability to genetic manipulation. Maraba virus, a recently identified vesiculovirus, is a single-stranded negative-sense RNA virus with a favorable safety profile and minimal pre-existing immunity in humans. It demonstrates selective tumor tropism partly through low-density lipoprotein receptor (LDLR)-mediated entry and impaired antiviral responses in cancer cells. Genetic engineering of the wild-type Maraba virus led to the development of the MG1 strain, characterized by enhanced tumor selectivity, increased replication capacity, and potent cytolytic activity. Preclinical studies have demonstrated its efficacy as a monotherapy, a cancer vaccine vector expressing tumor-associated antigens, and in combination with chemotherapy and immune checkpoint inhibitors. MG1 also reshapes the tumor microenvironment, converting immunologically “cold” tumors into “hot” tumors, thereby enhancing immune-mediated tumor clearance. Compared to vesicular stomatitis virus, Maraba virus exhibits improved safety and reduced neurovirulence while maintaining strong oncolytic potential. This review aims to comprehensively summarize the biological characteristics of the MG1 Maraba virus, its genetic development, mechanisms of action, and current preclinical and clinical applications as a novel oncolytic immunotherapeutic agent. Full article

Vesicular stomatitis virus (VSV), a member of the Vesiculovirus genus within the Rhabdoviridae family, is a widespread pathogen affecting all hoofed livestock species, leading to reduced animal growth and productivity. To date, no effective therapeutic treatment for VSV infection has been developed. Natural medicinal compounds with immunomodulatory properties represent a promising supportive strategy for infection control. Ginsenoside Rh1, a primary bioactive component of ginseng plants, has been reported to possess broad pharmacological and immunoregulatory activities. Nevertheless, its potential antiviral effects against VSV remain unexplored. In this study, we demonstrate that Ginsenoside Rh1 exhibits considerable antiviral activity against VSV in cellular models. Mechanistically, its antiviral effect is primarily mediated through the inhibition of VSV-induced autophagy, thereby enhancing interferon-mediated antiviral responses. Collectively, our findings identify Ginsenoside Rh1 as a novel antiviral agent active against VSV and potentially related vesiculoviruses, clarify its mechanism of action, and highlight an autophagy-dependent immunomodulatory approach that could be critical for confronting existing and emerging RNA viral infections. Full article

Chandipura virus (CHPV) is a vesiculovirus that is a member of Rhabdviridae and is an encephalitic pathogen responsible for numerous epidemics in Central and Western India. The virus affects the brain and central nervous system mainly in children under 15 age of years, leading to neurological dysfunctions. Vectors that include sand flies, mosquitoes, and ticks are the main culprits in the transmission of CHPV. Five structural proteins (N, P, M, G, and L) encode the viral genome. The nucleocapsid protein N (N protein) encapsulates the viral genomic RNA in an RNase-resistant state, which plays a crucial role in the viral life cycle. Currently, no effective vaccine or therapeutics are available to treat the viral infection, and therefore efficient interventions are urgently needed. The repurposing of drugs is one of the best possible ways to controlCHPV infections in India and other parts of the world. In this study, we used a structure-based virtual screening approach by using FDA-approved drugs against the nucleocapsid protein of CHPV. The docking process identified a few drug candidates, which showed potent binding affinity towards the N protein. We used the Schrödinger Desmond v3.0 module; to compute the relative binding energies of ligands, we used the premier mm-GBSA module. Based on a short molecular dynamics simulation and prime MM-GBSA analysis, we identified Adrabetadex, Hydroxypropyl betadex, Beta-1,2,3,4,6-penta-O-Galloyl-D-Glucopyranose, thio-maltohexaose, and Indium-III pentetreotide as potent drug candidates for CHPV. Our computational results provide suggestions for in vitro and in vivo testing of these drugs against CHPV. Full article

In this study, we analyzed the potential of viral infections in the species Homo sapiens as environmental causes of orofacial clefts (OFCs). A scoring system was adapted for qualitatively assessing the potential of viruses to cause cleft lip and/or palate (CL/P). This assessment considered factors such as information from the literature, nucleotide and amino acid similarities, and the presence of Endogenous Viral Elements (EVEs). The analysis involved various algorithm packages within Basic Local Alignment Search Tool 2.13.0 software and databases from the National Center for Biotechnology Information and the International Committee on Taxonomy of Viruses. Twenty significant viral species using different biosynthesis strategies were identified: Human coronavirus NL63, Rio Negro virus, Alphatorquevirus homin9, Brisavirus, Cosavirus B, Torque teno mini virus 4, Bocaparvovirus primate2, Human coronavirus HKU1, Monkeypox virus, Mammarenavirus machupoense, Volepox virus, Souris mammarenavirus, Gammapapillomavirus 7, Betainfluenzavirus influenzae, Lymphocytic choriomeningitis mammarenavirus, Ledantevirus kern, Gammainfluenzavirus influenzae, Betapolyomavirus hominis, Vesiculovirus perinet, and Cytomegalovirus humanbeta5. The evident viral etiological potential in relation to CL/P varies depending on the Baltimore class to which the viral species belongs. Given the multifactorial nature of CL/P, this relationship appears to be dynamic. Full article

Snakehead vesiculovirus (SHVV), a strain of negative-stranded RNA viruses extracted from sick snakehead fish (Ophicephalus striatus), may pose a threat to the health of snakehead fish. Previous research has proved that the replication of SHVV can be significantly inhibited by glutamine starvation. To study how glutamine starvation inhibits SHVV replication, channel catfish ovary (CCO) cells with SHVV cultivated in the glutamine-free medium or the complete medium were used to investigate the differentially expressed proteins (DEPs). The results showed that 124 up-regulated and 246 down-regulated proteins were involved in many viral replication physiological processes, such as autophagy, post-translational modifications machinery, and functional pathways, including the PI3K-Akt signaling pathway and mTOR signaling pathway. Furthermore, a few proteins, such as Akt and Hsp90, which have been confirmed to be involved in the replication of RNA viruses, were also significantly differentially expressed. Taken together, our study demonstrated that glutamine starvation affects various functional pathways and the expression of some key proteins related to RNA viral replication, which will benefit future studies on the replication mechanisms of SHVV and the prevention of SHVV infection. Full article

Vesicular stomatitis Indiana virus (VSIV) of genus Vesiculovirus, species IndianaVesiculovirus (formerly as Vesicular stomatitis virus, VSV) causes a disease in livestock that is very similar to the foot and mouth disease, thereby an outbreak may lead to significant economic loss. Long-read sequencing (LRS) -based approaches already reveal a hidden complexity of the transcriptomes in several viruses. This technique has been utilized for the sequencing of the VSIV genome, but our study is the first for the application of this technique for the profiling of the VSIV transcriptome. Since LRS is able to sequence full-length RNA molecules, it thereby provides more accurate annotation of the transcriptomes than the traditional short-read sequencing methods. The objectives of this study were to assemble the complete transcriptome of using nanopore sequencing, to ascertain cell-type specificity and dynamics of viral gene expression, and to evaluate host gene expression changes induced by the viral infection. We carried out a time-course analysis of VSIV gene expression in human glioblastoma and primate fibroblast cell lines using a nanopore-based LRS approach and applied both amplified and direct cDNA sequencing (as well as cap-selection) for a fraction of samples. Our investigations revealed that, although the VSIV genome is simple, it generates a relatively complex transcriptomic architecture. In this study, we also demonstrated that VSIV transcripts vary in structure and exhibit differential gene expression patterns in the two examined cell types. Full article

Vesicular stomatitis (VS) is a reportable viral disease which affects horses, cattle, and pigs in the Americas. Outbreaks of vesicular stomatitis virus New Jersey serotype (VSV-NJ) in the United States typically occur on a 5–10-year cycle, usually affecting western and southwestern states. In 2019–2020, an outbreak of VSV Indiana serotype (VSV-IN) extended eastward into the states of Kansas and Missouri for the first time in several decades, leading to 101 confirmed premises in Kansas and 37 confirmed premises in Missouri. In order to investigate which vector species contributed to the outbreak in Kansas, we conducted insect surveillance at two farms that experienced confirmed VSV-positive cases, one each in Riley County and Franklin County. Centers for Disease Control and Prevention miniature light traps were used to collect biting flies on the premises. Two genera of known VSV vectors, Culicoides biting midges and Simulium black flies, were identified to species, pooled by species, sex, reproductive status, and collection site, and tested for the presence of VSV-IN RNA by RT-qPCR. In total, eight positive pools were detected from Culicoides sonorensis (1), Culicoides stellifer (3), Culicoides variipennis (1), and Simulium meridionale (3). The C. sonorensis- and C. variipennis-positive pools were from nulliparous individuals, possibly indicating transovarial or venereal transmission as the source of virus. This is the first report of VSV-IN in field caught C. stellifer and the first report of either serotype in S. meridionale near outbreak premises. These results improve our understanding of the role midges and black flies play in VSV epidemiology in the United States and broadens the scope of vector species for targeted surveillance and control. Full article

Vesicular stomatitis virus (VSV), which belongs to the Vesiculovirus genus of the family Rhabdoviridae, is a well studied livestock pathogen and prototypic non-segmented, negative-sense RNA virus. Although VSV is responsible for causing economically significant outbreaks of vesicular stomatitis in cattle, horses, and swine, the virus also represents a valuable research tool for molecular biologists and virologists. Indeed, the establishment of a reverse genetics system for the recovery of infectious VSV from cDNA transformed the utility of this virus and paved the way for its use as a vaccine vector. A highly effective VSV-based vaccine against Ebola virus recently received clinical approval, and many other VSV-based vaccines have been developed, particularly for high-consequence viruses. This review seeks to provide a holistic but concise overview of VSV, covering the virus’s ascension from perennial agricultural scourge to promising medical countermeasure, with a particular focus on vaccines. Full article

Bat flies (Hippoboscoidea: Nycteribiidae and Streblidae) are obligate hematophagous ectoparasites of bats. We collected streblid bat flies from the New World (México) and the Old World (Uganda), and used metagenomics to identify their viruses. In México, we found méjal virus (Rhabdoviridae; Vesiculovirus), Amate virus (Reoviridae: Orbivirus), and two unclassified viruses of invertebrates. Méjal virus is related to emerging zoonotic encephalitis viruses and to the agriculturally important vesicular stomatitis viruses (VSV). Amate virus and its sister taxon from a bat are most closely related to mosquito- and tick-borne orbiviruses, suggesting a previously unrecognized orbivirus transmission cycle involving bats and bat flies. In Uganda, we found mamucuso virus (Peribunyaviridae: Orthobunyavirus) and two unclassified viruses (a rhabdovirus and an invertebrate virus). Mamucuso virus is related to encephalitic viruses of mammals and to viruses from nycteribiid bat flies and louse flies, suggesting a previously unrecognized orthobunyavirus transmission cycle involving hippoboscoid insects. Bat fly virus transmission may be neither strictly vector-borne nor strictly vertical, with opportunistic feeding by bat flies occasionally leading to zoonotic transmission. Many “bat-associated” viruses, which are ecologically and epidemiologically associated with bats but rarely or never found in bats themselves, may actually be viruses of bat flies or other bat ectoparasites. Full article

Bats, the second largest order of mammals worldwide, harbor specific characteristics such as sustaining flight, a special immune system, unique habits, and ecological niches. In addition, they are the natural reservoirs of a variety of emerging or re-emerging zoonotic pathogens. Rhabdoviridae is one of the most diverse families of RNA viruses, which consists of 20 ecologically diverse genera, infecting plants, mammals, birds, reptiles, and fish. To date, three bat-related genera are described, named Lyssavirus, Vesiculovirus, and Ledantevirus. However, the prevalence and the distribution of these bat-related rhabdoviruses remain largely unknown, especially in China. To fill this gap, we performed a large molecular retrospective study based on the real-time reverse transcription polymerase chain reaction (RT-qPCR) detection of lyssavirus in bat samples (1044 brain and 3532 saliva samples, from 63 different bat species) originating from 21 provinces of China during 2006–2018. None of them were positive for lyssavirus, but six bat brains (0.6%) of Rhinolophus bat species, originating from Hubei and Hainan provinces, were positive for vesiculoviruses or ledanteviruses. Based on complete genomes, these viruses were phylogenetically classified into three putative new species, tentatively named Yinshui bat virus (YSBV), Taiyi bat virus (TYBV), and Qiongzhong bat virus (QZBV). These results indicate the novel rhabdoviruses circulated in different Chinese bat populations. Full article

Bats are a host and reservoir for a large number of viruses, many of which are zoonotic. In North America, the big brown bat (Eptesicus fuscus) is widely distributed and common. Big brown bats are a known reservoir for rabies virus, which, combined with their propensity to roost in human structures, necessitates testing for rabies virus following human exposure. The current pandemic caused by severe acute respiratory syndrome coronavirus 2, likely of bat origin, illustrates the need for continued surveillance of wildlife and bats for potentially emerging zoonotic viruses. Viral metagenomic sequencing was performed on 39 big brown bats and one hoary bat submitted for rabies testing due to human exposure in South Dakota. A new genotype of American bat vesiculovirus was identified in seven of 17 (41%) heart and lung homogenates at high levels in addition to two of 23 viscera pools. A second rhabdovirus, Sodak rhabdovirus 1 (SDRV1), was identified in four of 23 (17%) viscera pools. Phylogenetic analysis placed SDRV1 in the genus Alphanemrhavirus, which includes two recognized species that were identified in nematodes. Finally, a highly divergent rhabdovirus, Sodak rhabdovirus 2 (SDRV2), was identified in two of 23 (8.7%) big brown bats. Phylogenetic analysis placed SDRV2 as ancestral to the dimarhabdovirus supergroup and Lyssavirus. Intracranial inoculation of mouse pups with rhabdovirus-positive tissue homogenates failed to elicit clinical disease. Further research is needed to determine the zoonotic potential of these non-rabies rhabdoviruses. Full article

Virus-like vesicles (VLV) are hybrid vectors based on an evolved Semliki Forest virus (SFV) RNA replicon and the envelope glycoprotein (G) from vesicular stomatitis virus (VSV). Previously, we showed that VLV can be used to express protein antigens and generate protective antigen-specific CD8⁺ T cells. This report describes VLV vectors designed for enhanced protein expression and immunogenicity. Expressing hepatitis B virus (HBV) middle S antigen (MHBs) from VLV using a dual subgenomic promoter significantly increased MHBs-specific CD8⁺ T cell and antibody production in mice. Furthermore, envelope glycoprotein switch from VSV Indiana to the glycoprotein of Chandipura virus enabled prime-boost immunization and further increased responses to MHBs. Therapeutic efficacy was evaluated in a mouse model of chronic HBV infection initiated by HBV delivery with adeno-associated virus. Mice with lower or intermediate HBV antigen levels demonstrated a significant and sustained reduction of HBV replication following VLV prime-boost immunization. However, mice with higher HBV antigen levels showed no changes in HBV replication, emphasizing the importance of HBV antigenemia for implementing immunotherapies. This report highlights the potential of VLV dual promoter vectors to induce effective antigen-specific immune responses and informs the further development and evaluation of hybrid viral vaccine platforms for preventative and therapeutic purposes. Full article

Viruses are ubiquitous and diverse microorganisms arising as a result of interactions within their vertebrate and invertebrate hosts. Here we report the presence of different viruses in the salivary glands of 1657 mosquitoes classified over 28 culicinae species from the North region of the Brazilian Pantanal wetland through metagenomics, viral isolation, and RT-PCR. In total, 12 viruses were found, eight putative novel viruses with relatively low similarity with pre-existing species of viruses within their families, named Pirizal iflavirus, Furrundu phlebovirus, Pixé phlebovirus, Guampa vesiculovirus, Chacororé flavivirus, Rasqueado orbivirus, Uru chuvirus, and Bororo circovirus. We also found the already described Lobeira dielmorhabdovirus, Sabethes flavivirus, Araticum partitivirus, and Murici totivirus. Therefore, these findings underscore the vast diversity of culicinae and novel viruses yet to be explored in Pantanal, the largest wetland on the planet. Full article