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21 pages, 4568 KiB

Open AccessFeature PaperArticle

Exploring the Molecular Basis of Vesicular Stomatitis Virus Pathogenesis in Swine: Insights from Expression Profiling of Primary Macrophages Infected with M51R Mutant Virus

by Lauro Velazquez-Salinas, Gisselle N. Medina, Federico Valdez, Selene Zarate, Shannon Collinson, James J. Zhu and Luis L. Rodriguez

Pathogens 2023, 12(7), 896; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens12070896 - 30 Jun 2023

Cited by 1 | Viewed by 1157

Abstract

Vesicular stomatitis virus (VSV) is an emergent virus affecting livestock in the US. Previously, using a recombinant VSV carrying the M51R mutation in the matrix protein (rNJ0612NME6-M51R), we evaluated the pathogenesis of this virus in pigs. Our results indicated that rNJ0612NME6-M51R represented an [...] Read more.

Vesicular stomatitis virus (VSV) is an emergent virus affecting livestock in the US. Previously, using a recombinant VSV carrying the M51R mutation in the matrix protein (rNJ0612NME6-M51R), we evaluated the pathogenesis of this virus in pigs. Our results indicated that rNJ0612NME6-M51R represented an attenuated phenotype in in-vivo and in ex-vivo in pig macrophages, resembling certain clinical features observed in field VSV isolates. In order to gain more insight into the molecular basis leading to the attenuation of rNJ0612NME6-M51R in pigs, we conducted a microarray analysis to assess the gene expression profiles of primary porcine macrophages infected with rNJ0612NME6-M51R compared to its parental virus (rNJ0612NME6). Our results showed an overall higher gene expression in macrophages infected with rNJ0612NME6-M51R. Specifically, we observed that the pathways related with immune cytokine signaling and interferon (IFN)-related responses (including activation, signaling, induction, and antiviral mechanisms) were the ones comprising most of the relevant genes identified during this study. Collectively, the results presented herein highlight the relevance of type I interferon during the pathogenesis of VSV in pigs. The information generated from this study may represent a framework for future studies intended to understand the molecular bases of the pathogenesis of field strains in livestock. Full article

(This article belongs to the Special Issue Vesicular Stomatitis Virus: Agricultural Pathogen and Human Medical Research Tool)

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20 pages, 1920 KiB

Open AccessArticle

Surveillance along the Rio Grande during the 2020 Vesicular Stomatitis Outbreak Reveals Spatio-Temporal Dynamics of and Viral RNA Detection in Black Flies

by Katherine I. Young, Federico Valdez, Christina Vaquera, Carlos Campos, Lawrence Zhou, Helen K. Vessels, J. Kevin Moulton, Barbara S. Drolet, Paula Rozo-Lopez, Angela M. Pelzel-McCluskey, Debra C. Peters, Luis L. Rodriguez and Kathryn A. Hanley

Pathogens 2021, 10(10), 1264; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10101264 - 01 Oct 2021

Cited by 3 | Viewed by 2785

Abstract

Vesicular stomatitis virus (VSV) emerges periodically from its focus of endemic transmission in southern Mexico to cause epizootics in livestock in the US. The ecology of VSV involves a diverse, but largely undefined, repertoire of potential reservoir hosts and invertebrate vectors. As part [...] Read more.

Vesicular stomatitis virus (VSV) emerges periodically from its focus of endemic transmission in southern Mexico to cause epizootics in livestock in the US. The ecology of VSV involves a diverse, but largely undefined, repertoire of potential reservoir hosts and invertebrate vectors. As part of a larger program to decipher VSV transmission, we conducted a study of the spatiotemporal dynamics of Simulium black flies, a known vector of VSV, along the Rio Grande in southern New Mexico, USA from March to December 2020. Serendipitously, the index case of VSV-Indiana (VSIV) in the USA in 2020 occurred at a central point of our study. Black flies appeared soon after the release of the Rio Grande’s water from an upstream dam in March 2020. Two-month and one-year lagged precipitation, maximum temperature, and vegetation greenness, measured as Normalized Difference Vegetation Index (NDVI), were associated with increased black fly abundance. We detected VSIV RNA in 11 pools comprising five black fly species using rRT-PCR; five pools yielded a VSIV sequence. To our knowledge, this is the first detection of VSV in the western US from vectors that were not collected on premises with infected domestic animals. Full article

(This article belongs to the Special Issue Vesicular Stomatitis Virus: Agricultural Pathogen and Human Medical Research Tool)

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21 pages, 606 KiB

Open AccessArticle

Molecular Pathogenesis and Immune Evasion of Vesicular Stomatitis New Jersey Virus Inferred from Genes Expression Changes in Infected Porcine Macrophages

by Lauro Velazquez-Salinas, Jessica A. Canter, James J. Zhu and Luis L. Rodriguez

Pathogens 2021, 10(9), 1134; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10091134 - 03 Sep 2021

Cited by 2 | Viewed by 2630

Abstract

The molecular mechanisms associated with the pathogenesis of vesicular stomatitis virus (VSV) in livestock remain poorly understood. Several studies have highlighted the relevant role of macrophages in controlling the systemic dissemination of VSV during infection in different animal models, including mice, cattle, and [...] Read more.

The molecular mechanisms associated with the pathogenesis of vesicular stomatitis virus (VSV) in livestock remain poorly understood. Several studies have highlighted the relevant role of macrophages in controlling the systemic dissemination of VSV during infection in different animal models, including mice, cattle, and pigs. To gain more insight into the molecular mechanisms used by VSV to impair the immune response in macrophages, we used microarrays to determine the transcriptomic changes produced by VSV infection in primary cultures of porcine macrophages. The results indicated that VSV infection induced the massive expression of multiple anorexic, pyrogenic, proinflammatory, and immunosuppressive genes. Overall, the interferon (IFN) response appeared to be suppressed, leading to the absence of stimulation of interferon-stimulated genes (ISG). Interestingly, VSV infection promoted the expression of several genes known to downregulate the expression of IFNβ. This represents an alternate mechanism for VSV control of the IFN response, beyond the recognized mechanisms mediated by the matrix protein. Although there was no significant differential gene expression in macrophages infected with a highly virulent epidemic strain compared to a less virulent endemic strain, the endemic strain consistently induced higher expression of all upregulated cytokines and chemokines. Collectively, this study provides novel insights into VSV molecular pathogenesis and immune evasion that warrant further investigation. Full article

(This article belongs to the Special Issue Vesicular Stomatitis Virus: Agricultural Pathogen and Human Medical Research Tool)

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12 pages, 1535 KiB

Open AccessArticle

Detection of Vesicular Stomatitis Virus Indiana from Insects Collected during the 2020 Outbreak in Kansas, USA

by Bethany L. McGregor, Paula Rozo-Lopez, Travis M. Davis and Barbara S. Drolet

Pathogens 2021, 10(9), 1126; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10091126 - 02 Sep 2021

Cited by 8 | Viewed by 2789

Abstract

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 [...] Read more.

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

(This article belongs to the Special Issue Vesicular Stomatitis Virus: Agricultural Pathogen and Human Medical Research Tool)

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10 pages, 514 KiB

Open AccessFeature PaperArticle

Identical Viral Genetic Sequence Found in Black Flies (Simulium bivittatum) and the Equine Index Case of the 2006 U.S. Vesicular Stomatitis Outbreak

by Barbara S. Drolet, Will K. Reeves, Kristine E. Bennett, Steven J. Pauszek, Miranda R. Bertram and Luis L. Rodriguez

Pathogens 2021, 10(8), 929; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10080929 - 23 Jul 2021

Cited by 6 | Viewed by 2195

Abstract

In 2006, vesicular stomatitis New Jersey virus (VSNJV) caused outbreaks in Wyoming (WY) horses and cattle after overwintering in 2004 and 2005. Within two weeks of the outbreak onset, 12,203 biting flies and 194 grasshoppers were collected near three equine-positive premises in Natrona [...] Read more.

In 2006, vesicular stomatitis New Jersey virus (VSNJV) caused outbreaks in Wyoming (WY) horses and cattle after overwintering in 2004 and 2005. Within two weeks of the outbreak onset, 12,203 biting flies and 194 grasshoppers were collected near three equine-positive premises in Natrona County, WY. Insects were identified to the species level and tested by RT-qPCR for VSNJV polymerase (L) and phosphoprotein (P) gene RNA. Collected dipterans known to be competent for VSV transmission included Simulium black flies and Culicoides biting midges. VSNJV L and P RNA was detected in two pools of female Simulium bivittatum and subjected to partial genome sequencing. Phylogenetic analysis based on the hypervariable region of the P gene from black flies showed 100% identity to the isolate obtained from the index horse case on the same premises. This is the first report of VSNJV in S. bivittatum in WY and the first field evidence of possible VSV maintenance in black fly populations during an outbreak. Full article

(This article belongs to the Special Issue Vesicular Stomatitis Virus: Agricultural Pathogen and Human Medical Research Tool)

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14 pages, 1300 KiB

Open AccessArticle

Impacts of Infectious Dose, Feeding Behavior, and Age of Culicoides sonorensis Biting Midges on Infection Dynamics of Vesicular Stomatitis Virus

by Paula Rozo-Lopez, Berlin Londono-Renteria and Barbara S. Drolet

Pathogens 2021, 10(7), 816; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10070816 - 29 Jun 2021

Cited by 9 | Viewed by 2797

Abstract

Culicoides sonorensis biting midges are biological vectors of vesicular stomatitis virus (VSV) in the U.S. Yet, little is known regarding the amount of ingested virus required to infect midges, nor how their feeding behavior or age affects viral replication and vector competence. We [...] Read more.

Culicoides sonorensis biting midges are biological vectors of vesicular stomatitis virus (VSV) in the U.S. Yet, little is known regarding the amount of ingested virus required to infect midges, nor how their feeding behavior or age affects viral replication and vector competence. We determined the minimum infectious dose of VSV-New Jersey for C. sonorensis midges and examined the effects of multiple blood-feeding cycles and age at the time of virus acquisition on infection dynamics. A minimum dose of 3.2 logs of virus/mL of blood resulted in midgut infections, and 5.2 logs/mL resulted in a disseminated infection to salivary glands. For blood-feeding behavior studies, ingestion of one or two non-infectious blood meals (BM) after a VSV infectious blood meal (VSV-BM) resulted in higher whole-body virus titers than midges receiving only the single infectious VSV-BM. Interestingly, this infection enhancement was not seen when a non-infectious BM preceded the infectious VSV-BM. Lastly, increased midge age at the time of infection correlated to increased whole-body virus titers. This research highlights the epidemiological implications of infectious doses, vector feeding behaviors, and vector age on VSV infection dynamics to estimate the risk of transmission by Culicoides midges more precisely. Full article

(This article belongs to the Special Issue Vesicular Stomatitis Virus: Agricultural Pathogen and Human Medical Research Tool)

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Review

Jump to: Research

20 pages, 3787 KiB

Open AccessReview

Vesicular Stomatitis Virus: From Agricultural Pathogen to Vaccine Vector

by Guodong Liu, Wenguang Cao, Abdjeleel Salawudeen, Wenjun Zhu, Karla Emeterio, David Safronetz and Logan Banadyga

Pathogens 2021, 10(9), 1092; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10091092 - 27 Aug 2021

Cited by 23 | Viewed by 6420

Abstract

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 [...] Read more.

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

(This article belongs to the Special Issue Vesicular Stomatitis Virus: Agricultural Pathogen and Human Medical Research Tool)

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19 pages, 2160 KiB

Open AccessReview

Review of Vesicular Stomatitis in the United States with Focus on 2019 and 2020 Outbreaks

by Angela Pelzel-McCluskey, Brad Christensen, John Humphreys, Miranda Bertram, Robert Keener, Robert Ewing, Lee W. Cohnstaedt, Rachel Tell, Debra P. C. Peters and Luis Rodriguez

Pathogens 2021, 10(8), 993; https://0-doi-org.brum.beds.ac.uk/10.3390/pathogens10080993 - 06 Aug 2021

Cited by 10 | Viewed by 2574

Abstract

Vesicular stomatitis (VS) is a vector-borne livestock disease caused by vesicular stomatitis New Jersey virus (VSNJV) or vesicular stomatitis Indiana virus (VSIV). The disease circulates endemically in northern South America, Central America, and Mexico and only occasionally causes outbreaks in the United States. [...] Read more.

Vesicular stomatitis (VS) is a vector-borne livestock disease caused by vesicular stomatitis New Jersey virus (VSNJV) or vesicular stomatitis Indiana virus (VSIV). The disease circulates endemically in northern South America, Central America, and Mexico and only occasionally causes outbreaks in the United States. Over the past 20 years, VSNJV outbreaks in the southwestern and Rocky Mountain regions occurred with incursion years followed by virus overwintering and subsequent expansion outbreak years. Regulatory response by animal health officials is deployed to prevent spread from lesioned animals. The 2019 VS incursion was the largest in 40 years, lasting from June to December 2019 with 1144 VS-affected premises in 111 counties in eight states (Colorado, Kansas, Nebraska, New Mexico, Oklahoma, Texas, Utah, and Wyoming) and was VSIV serotype, last isolated in 1998. A subsequent expansion occurred from April to October 2020 with 326 VS-affected premises in 70 counties in eight states (Arizona, Arkansas, Kansas, Missouri, Nebraska, New Mexico, Oklahoma, and Texas). The primary serotype in 2020 was VSIV, but a separate incursion of VSNJV occurred in south Texas. Summary characteristics of the outbreaks are presented along with VSV-vector sampling results and phylogenetic analysis of VSIV isolates providing evidence of virus overwintering. Full article

(This article belongs to the Special Issue Vesicular Stomatitis Virus: Agricultural Pathogen and Human Medical Research Tool)

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