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Vesicular Stomatitis Virus (VSV)

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A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (15 January 2025) | Viewed by 19072

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Dr. Chad Mire

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Guest Editor

Foreign Arthropod Animal Disease Research Unit, USDA-ARS, NBAF, Manhattan, KS 66502, USA
Interests: arboviruses; filoviruses; henipaviruses; pathogenesis; vaccines; therapeutics; vector–host–pathogen interaction
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Dr. Luis L. Rodriguez

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USDA ARS Plum Island Animal Disease Center, Greenport, NY, USA
Interests: virus
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Dr. Andrea Marzi

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Laboratory of Virology, DIR, NIAID, NIH, 903 South 4th Street, Hamilton, MT 59840, USA
Interests: emerging viruses; filoviruses; VSV; pathogenesis; animal models; vaccines; therapeutics; host–pathogen interactions
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Prof. Dr. Michael A. Whitt

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Guest Editor

University of Tennessee Health Science Center, Memphis, TN, USA
Interests: rhabdovirus assembly and the development of VSV-based targeting vectors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Vesicular stomatitis virus (VSV) is a vector-borne rhabdovirus affecting horses, cattle, swine, small ruminants, lamas, and alpacas, among other species. In cattle and pigs, the disease resembles foot and mouth disease, a devastating transboundary animal disease. Humans can become infected when handling affected animals, or in laboratory exposures, causing non-lethal flu-like illness. Incursions of VSV into the US from endemic regions in Southern Mexico occur sporadically at 5–10-year intervals. However, the epidemiology and environmental factors mediating incursion and transmission remain poorly understood. In addition to being a pathogen of agricultural concern, VSV is the prototype single-stranded negative-sense RNA virus used to understand molecular virology, virus evolution, viral transcription and replication, innate immune evasion, and adaptive immune response to viral infections. This knowledge has come from classical virology and from reverse genetics. VSV was among the first negative-strand RNA viruses to have a reverse genetic system, which led to the development of VSV as a vaccine vector, in immune therapy, and as an oncolytic virus vector used in human clinical trials.

In this Special Issue, we will explore novel insights into VSV and address long-standing unanswered questions about disease ecology, pathogenesis, and how VSV became a tool to fight infectious diseases and cancer. Topics covered will include the following: pathogenesis, innate immune evasion, virus–vector interactions, virus–host interactions, epidemiology, entry, assembly, replication, transcription, vaccine platforms, and vectored oncolytics.

Dr. Chad Mire
Dr. Luis L. Rodriguez
Dr. Andrea Marzi
Prof. Dr. Michael A. Whitt
Guest Editors

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Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

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Keywords

pathogenesis
innate immune evasion
Virus–vector interactions
Virus–host interactions
epidemiology
entry
assembly
replication
transcription
vaccine
oncolytic

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Vesicular Stomatitis Virus (VSV) 2025 in Viruses

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18 pages, 6964 KiB

Open AccessArticle

Leveraging Synthetic Virology for the Rapid Engineering of Vesicular Stomatitis Virus (VSV)

by Chad M. Moles, Rupsa Basu, Peter Weijmarshausen, Brenda Ho, Manal Farhat, Taylor Flaat and Bruce F. Smith

Viruses 2024, 16(10), 1641; https://doi.org/10.3390/v16101641 - 21 Oct 2024

Viewed by 3033

Abstract

Vesicular stomatitis virus (VSV) is a prototype RNA virus that has been instrumental in advancing our understanding of viral molecular biology and has applications in vaccine development, cancer therapy, antiviral screening, and more. Current VSV genome plasmids for purchase or contract virus services provide limited options for modification, restricted to predefined cloning sites and insert locations. Improved methods and tools to engineer VSV will unlock further insights into long-standing virology questions and new opportunities for innovative therapies. Here, we report the design and construction of a full-length VSV genome. The 11,161 base pair synthetic VSV (synVSV) was assembled from four modularized DNA fragments. Following rescue and titration, phenotypic analysis showed no significant differences between natural and synthetic viruses. To demonstrate the utility of a synthetic virology platform, we then engineered VSV with a foreign glycoprotein, a common use case for studying viral entry and developing anti-virals. To show the freedom of design afforded by this platform, we then modified the genome of VSV by rearranging the gene order, switching the positions of VSV-P and VSV-M genes. This work represents a significant technical advance, providing a flexible, cost-efficient platform for the rapid construction of VSV genomes, facilitating the development of innovative therapies. Full article

(This article belongs to the Special Issue Vesicular Stomatitis Virus (VSV))

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17 pages, 12790 KiB

Open AccessArticle

Vesicular Stomatitis Virus Detected in Biting Midges and Black Flies during the 2023 Outbreak in Southern California

by Stacey L. P. Scroggs, Dustin A. Swanson, Taylor D. Steele, Amy R. Hudson, Lindsey M. Reister-Hendricks, Jessica Gutierrez, Phillip Shults, Bethany L. McGregor, Caitlin E. Taylor, Travis M. Davis, Nadine Lamberski, Kristen A. Phair, Lauren L. Howard, Nathan E. McConnell, Nikos Gurfield, Barbara S. Drolet, Angela M. Pelzel-McCluskey and Lee W. Cohnstaedt

Viruses 2024, 16(9), 1428; https://doi.org/10.3390/v16091428 - 7 Sep 2024

Cited by 1 | Viewed by 1955

Abstract

Vesicular stomatitis (VS) is a viral disease that affects horses, cattle, and swine that is transmitted by direct contact and hematophagous insects. In 2023, a multi-state outbreak of vesicular stomatitis New Jersey virus (VSNJV) occurred in California, Nevada, and Texas, infecting horses, cattle, and rhinoceros. To identify possible insect vectors, we conducted insect surveillance at various locations in San Diego County, CA, including at a wildlife park. CO₂ baited traps set from mid-May to mid-August 2023 collected 2357 Culicoides biting midges and 1215 Simulium black flies, which are insect genera implicated in VSNJV transmission. Insects were pooled by species, location, and date, then tested for viral RNA. Nine RNA-positive pools of Culicoides spp. and sixteen RNA-positive pools of Simulium spp were detected. Infectious virus was detected by cytopathic effect in 96% of the RNA-positive pools. This is the first report of VSNJV in wild-caught C. bergi, C. freeborni, C. occidentalis, S. argus, S. hippovorum, and S. tescorum. The vector competency of these species for VSNJV has yet to be determined but warrants examination. Active vector surveillance and testing during disease outbreaks increases our understanding of the ecology and epidemiology of VS and informs vector control efforts. Full article

(This article belongs to the Special Issue Vesicular Stomatitis Virus (VSV))

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20 pages, 1246 KiB

Open AccessArticle

Modeling the 2014–2015 Vesicular Stomatitis Outbreak in the United States Using an SEIR-SEI Approach

by John M. Humphreys, Angela M. Pelzel-McCluskey, Phillip T. Shults, Lauro Velazquez-Salinas, Miranda R. Bertram, Bethany L. McGregor, Lee W. Cohnstaedt, Dustin A. Swanson, Stacey L. P. Scroggs, Chad Fautt, Amber Mooney, Debra P. C. Peters and Luis L. Rodriguez

Viruses 2024, 16(8), 1315; https://doi.org/10.3390/v16081315 - 18 Aug 2024

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Abstract

Vesicular stomatitis (VS) is a vector-borne livestock disease caused by the vesicular stomatitis New Jersey virus (VSNJV). This study presents the first application of an SEIR-SEI compartmental model to analyze VSNJV transmission dynamics. Focusing on the 2014–2015 outbreak in the United States, the model integrates vertebrate hosts and insect vector demographics while accounting for heterogeneous competency within the populations and observation bias in documented disease cases. Key epidemiological parameters were estimated using Bayesian inference and Markov chain Monte Carlo (MCMC) methods, including the force of infection, effective reproduction number (

R_{t}

), and incubation periods. The model revealed significant underreporting, with only 10–24% of infections documented, 23% of which presented with clinical symptoms. These findings underscore the importance of including competence and imperfect detection in disease models to depict outbreak dynamics and inform effective control strategies accurately. As a baseline model, this SEIR-SEI implementation is intended to serve as a foundation for future refinements and expansions to improve our understanding of VS dynamics. Enhanced surveillance and targeted interventions are recommended to manage future VS outbreaks. Full article

(This article belongs to the Special Issue Vesicular Stomatitis Virus (VSV))

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22 pages, 3367 KiB

Open AccessArticle

Efficacy and Immunogenicity of a Recombinant Vesicular Stomatitis Virus-Vectored Marburg Vaccine in Cynomolgus Macaques

by Vidyleison N. Camargos, Shannan L. Rossi, Terry L. Juelich, Jennifer K. Smith, Nikos Vasilakis, Alexander N. Freiberg, Rick Nichols and Joan Fusco

Viruses 2024, 16(8), 1181; https://doi.org/10.3390/v16081181 - 24 Jul 2024

Cited by 1 | Viewed by 1573

Abstract

Filoviruses, like the Marburg (MARV) and Ebola (EBOV) viruses, have caused outbreaks associated with significant hemorrhagic morbidity and high fatality rates. Vaccines offer one of the best countermeasures for fatal infection, but to date only the EBOV vaccine has received FDA licensure. Given the limited cross protection between the EBOV vaccine and Marburg hemorrhagic fever (MHF), we analyzed the protective efficacy of a similar vaccine, rVSV-MARV, in the lethal cynomolgus macaque model. NHPs vaccinated with a single dose (as little as 1.6 × 10⁷ pfu) of rVSV-MARV seroconverted to MARV G-protein prior to challenge on day 42. Vaccinemia was measured in all vaccinated primates, self-resolved by day 14 post vaccination. Importantly, all vaccinated NHPs survived lethal MARV challenge, and showed no significant alterations in key markers of morbid disease, including clinical signs, and certain hematological and clinical chemistry parameters. Further, apart from one primate (from which tissues were not collected and no causal link was established), no pathology associated with Marburg disease was observed in vaccinated animals. Taken together, rVSV-MARV is a safe and efficacious vaccine against MHF in cynomolgus macaques. Full article

(This article belongs to the Special Issue Vesicular Stomatitis Virus (VSV))

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24 pages, 2175 KiB

Open AccessArticle

Interrogating Genomes and Geography to Unravel Multiyear Vesicular Stomatitis Epizootics

by John M. Humphreys, Phillip T. Shults, Lauro Velazquez-Salinas, Miranda R. Bertram, Angela M. Pelzel-McCluskey, Steven J. Pauszek, Debra P. C. Peters and Luis L. Rodriguez

Viruses 2024, 16(7), 1118; https://doi.org/10.3390/v16071118 - 11 Jul 2024

Cited by 1 | Viewed by 1951

Abstract

We conducted an integrative analysis to elucidate the spatial epidemiological patterns of the Vesicular Stomatitis New Jersey virus (VSNJV) during the 2014–15 epizootic cycle in the United States (US). Using georeferenced VSNJV genomics data, confirmed vesicular stomatitis (VS) disease cases from surveillance, and a suite of environmental factors, our study assessed environmental and phylogenetic similarity to compare VS cases reported in 2014 and 2015. Despite uncertainties from incomplete virus sampling and cross-scale spatial processes, patterns suggested multiple independent re-invasion events concurrent with potential viral overwintering between sequential seasons. Our findings pointed to a geographically defined southern virus pool at the US–Mexico interface as the source of VSNJV invasions and overwintering sites. Phylodynamic analysis demonstrated an increase in virus diversity before a rise in case numbers and a pronounced reduction in virus diversity during the winter season, indicative of a genetic bottleneck and a significant narrowing of virus variation between the summer outbreak seasons. Environment–vector interactions underscored the central role of meta-population dynamics in driving disease spread. These insights emphasize the necessity for location- and time-specific management practices, including rapid response, movement restrictions, vector control, and other targeted interventions. Full article

(This article belongs to the Special Issue Vesicular Stomatitis Virus (VSV))

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15 pages, 2552 KiB

Open AccessArticle

Development of Robust Freeze-Drying Process for Long-Term Stability of rVSV-SARS-CoV-2 Vaccine

by MD Faizul Hussain Khan, Maryam Youssef, Sean Nesdoly and Amine A. Kamen

Viruses 2024, 16(6), 942; https://doi.org/10.3390/v16060942 - 11 Jun 2024

Cited by 4 | Viewed by 2409

Abstract

The thermostability of vaccines, particularly enveloped viral vectored vaccines, remains a challenge to their delivery wherever needed. The freeze-drying of viral vectored vaccines is a promising approach but remains challenging due to the water removal process from the outer and inner parts of the virus. In the case of enveloped viruses, freeze-drying induces increased stress on the envelope, which often leads to the inactivation of the virus. In this study, we designed a method to freeze-dry a recombinant vesicular stomatitis virus (VSV) expressing the SARS-CoV-2 spike glycoprotein. Since the envelope of VSV is composed of 50% lipids and 50% protein, the formulation study focused on both the protein and lipid portions of the vector. Formulations were prepared primarily using sucrose, trehalose, and sorbitol as cryoprotectants; mannitol as a lyoprotectant; and histidine as a buffer. Initially, the infectivity of rVSV-SARS-CoV-2 and the cake stability were investigated at different final moisture content levels. High recovery of the infectious viral titer (~0.5 to 1 log loss) was found at 3–6% moisture content, with no deterioration in the freeze-dried cakes. To further minimize infectious viral titer loss, the composition and concentration of the excipients were studied. An increase from 5 to 10% in both the cryoprotectants and lyoprotectant, together with the addition of 0.5% gelatin, resulted in the improved recovery of the infectious virus titer and stable cake formation. Moreover, the secondary drying temperature of the freeze-drying process showed a significant impact on the infectivity of rVSV-SARS-CoV-2. The infectivity of the vector declined drastically when the temperature was raised above 20 °C. Throughout a long-term stability study, formulations containing 10% sugar (sucrose/trehalose), 10% mannitol, 0.5% gelatin, and 10 mM histidine showed satisfactory stability for six months at 2–8 °C. The development of this freeze-drying process and the optimized formulation minimize the need for a costly cold chain distribution system. Full article

(This article belongs to the Special Issue Vesicular Stomatitis Virus (VSV))

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10 pages, 1779 KiB

Open AccessCommunication

COVID-19 Serum Drives Spike-Mediated SARS-CoV-2 Variation

by Yuanling Yu, Mengyi Zhang, Lan Huang, Yanhong Chen, Xi Wu, Tao Li, Yanbo Li, Youchun Wang and Weijin Huang

Viruses 2024, 16(5), 763; https://doi.org/10.3390/v16050763 - 11 May 2024

Viewed by 2105

Abstract

Neutralizing antibodies targeting the spike (S) protein of SARS-CoV-2, elicited either by natural infection or vaccination, are crucial for protection against the virus. Nonetheless, the emergence of viral escape mutants presents ongoing challenges by contributing to breakthrough infections. To define the evolution trajectory of SARS-CoV-2 within the immune population, we co-incubated replication-competent rVSV/SARS-CoV-2/GFP chimeric viruses with sera from COVID-19 convalescents. Our findings revealed that the E484D mutation contributes to increased viral resistant against both convalescent and vaccinated sera, while the L1265R/H1271Y double mutation enhanced viral infectivity in 293T-hACE2 and Vero cells. These findings suggest that under the selective pressure of polyclonal antibodies, SARS-CoV-2 has the potential to accumulate mutations that facilitate either immune evasion or greater infectivity, facilitating its adaption to neutralizing antibody responses. Although the mutations identified in this study currently exhibit low prevalence in the circulating SARS-CoV-2 populations, the continuous and meticulous surveillance of viral mutations remains crucial. Moreover, there is an urgent necessity to develop next-generation antibody therapeutics and vaccines that target diverse, less mutation-prone antigenic sites to ensure more comprehensive and durable immune protection against SARS-CoV-2. Full article

(This article belongs to the Special Issue Vesicular Stomatitis Virus (VSV))

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Review

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21 pages, 310 KiB

Open AccessReview

Employing the Oncolytic Vesicular Stomatitis Virus in Cancer Virotherapy: Resistance and Clinical Considerations

by Alaa A. Abdelmageed, Stephen Dewhurst and Maureen C. Ferran

Viruses 2025, 17(1), 16; https://doi.org/10.3390/v17010016 - 25 Dec 2024

Viewed by 1357

Abstract

Vesicular Stomatitis Virus (VSV) has emerged as a promising candidate for various clinical applications, including vaccine development, virus pseudotyping, and gene delivery. Its broad host range, ease of propagation, and lack of pre-existing immunity in humans make it ideal for therapeutic use. VSV’s potential as an oncolytic virus has garnered attention; however, resistance to VSV-mediated oncolysis has been observed in some cell lines and tumor types, limiting its effectiveness. This review provides a detailed analysis of recent advances in VSV-based oncolysis, focusing on resistance mechanisms such as sustained type-I IFN signaling, upregulation of ISGs, immune cell activation, the tumor microenvironment (TME), and tumor-intrinsic factors. Strategies to overcome resistance include enhancing viral oncoselectivity, inhibiting IFN responses, modulating the TME, and combining VSV with chemotherapies, radiation, and immune checkpoint inhibitors. Several VSV-based phase I/II clinical trials show promise; however, addressing resistance and developing novel strategies to enhance therapeutic efficacy are essential for realizing the full potential of VSV oncolytic virotherapy. Future research should focus on patient-specific approaches, as tumor heterogeneity implies varying resistance mechanisms. Personalized treatments tailored to tumor molecular profiles, along with identifying biomarkers predictive of resistance to VSV oncolysis, will enhance patient selection and enable more effective, individualized VSV-based therapies. Full article

(This article belongs to the Special Issue Vesicular Stomatitis Virus (VSV))

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23 pages, 1102 KiB

Open AccessReview

Vesicular Stomatitis Virus: Insights into Pathogenesis, Immune Evasion, and Technological Innovations in Oncolytic and Vaccine Development

by Mohamed Mustaf Ahmed, Olalekan John Okesanya, Bonaventure Michael Ukoaka, Adamu Muhammad Ibrahim and Don Eliseo Lucero-Prisno III

Viruses 2024, 16(12), 1933; https://doi.org/10.3390/v16121933 - 18 Dec 2024

Cited by 1 | Viewed by 1796

Abstract

Vesicular stomatitis virus (VSV) represents a significant advancement in therapeutic medicine, offering unique molecular and cellular characteristics that make it exceptionally suitable for medical applications. The bullet-shaped morphology, RNA genome organization, and cytoplasmic replication strategy provide fundamental advantages for both vaccine development and oncolytic applications. VSV’s interaction with host cells through the low-density lipoprotein receptor (LDL-R) and its sophisticated transcriptional regulation mechanisms enables precise control over therapeutic applications. The virus demonstrates remarkable versatility through its rapid replication cycle, robust immune response induction, and natural neurotropism. Recent technological innovations in VSV engineering have led to enhanced safety protocols and improved therapeutic modifications, particularly in cancer treatment. Attenuation strategies have successfully addressed safety concerns while maintaining the therapeutic efficacy of the virus. The molecular and cellular interactions of VSV, particularly its immune modulation capabilities and tumor-selective properties, have proven valuable in the development of targeted therapeutic strategies. This review explores these aspects, while highlighting the continuing evolution of VSV-based therapeutic approaches in precision medicine. Full article

(This article belongs to the Special Issue Vesicular Stomatitis Virus (VSV))

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