Indiana vesiculovirus

Indiana vesiculovirus is the prototypic member of the genus Vesiculovirus of the family Rhabdoviridae. VSIV is an arbovirus, and its replication occurs in the cytoplasm. Natural VSIV infections encompass two steps, cytolytic infections of mammalian hosts and transmission by insects. In insects, infections are noncytolytic persistent. One confirmed vector of the virus is the phlebotomine sand fly Lutzomyia shannoni.{{cite web | vauthors = Mann RS, Kaufman PE, Butler JF | title = A Sand Fly, Lutzomyia shannoni Dyar (Insecta: Diptera: Psychodidae: Phlebotomine) | url = http://edis.ifas.ufl.edu/in797 | work = EENY-421. Entomology and Nematology. Florida Cooperative Extension Service. University of Florida IFAS | date = 2009 }} The genome of VSIV is on a single molecule of negative-sense RNA that has 11,161 nucleotides in length,{{cite web |title=VSV complete genome |url=https://www.ncbi.nlm.nih.gov/nuccore/?term=vsv+complete+genome |access-date=30 May 2013}} that encodes five major proteins: G protein (G), large protein (L), phosphoprotein (P), matrix protein (M) and nucleoprotein (N):

The VSIV G protein, aka VSVG, enables viral entry. It mediates viral attachment to an LDL receptor (LDLR) or an LDLR family member present on the host cell.Finkelshtein D, Werman A, Novick D, Barak S, Rubinstein M. LDL receptor and its family members serve as the cellular receptors for vesicular stomatitis virus. Proc Natl Acad Sci U S A. 2013 Apr 30;110(18):7306–11. Following binding, the VSIV-LDLR complex is rapidly endocytosed. It then mediates fusion of the viral envelope with the endosomal membrane. VSIV enters the cell through partially clathrin-coated vesicles; virus-containing vesicles contain more clathrin and clathrin adaptor than conventional vesicles. Virus-containing vesicles recruit components of the actin machinery for their interaction, thus inducing its own uptake. VSIV G does not follow the same path as most vesicles because transport of the G protein from the ER to the plasma membrane is interrupted by incubation at 15 °C. Under this condition, the molecules accumulate in both the ER and a subcellular vesicle fraction of low density called the lipid-rich vesicle fraction. The material in the lipid-rich vesicle fraction appears to be a post-ER intermediate in the transport process to the plasma membrane (PM). After infection, the VSIV G gene is expressed and is commonly studied as a model for N-linked glycosylation in the endoplasmic reticulum (ER). It is translated into the rough ER where the Glc₃-Man₉-GlcNac₂ oligosaccharide is added by a dolichol-containing protein, to an NXS motif on VSIV G. Sugars are removed gradually as the protein travels to the Golgi apparatus, and it becomes resistant to endoglycosidase H.{{cite book | chapter = Transport from the ER through the Golgi Apparatus | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK26941/ | title = Molecular Biology of the Cell | edition = Fourth | first1 = Bruce | last1 = Alberts | first2 = Alexander | last2 = Johnson | first3 = Julian | last3 = Lewis | first4 = Martin | last4 = Raff | first5 = Keith | last5 = Roberts | first6 = Peter | last6 = Walter | name-list-style = vanc | location = New York | publisher = Garland Science | year = 2002 }} When synthesized in polarized epithelial cells, the envelope glycoprotein VSV G is targeted to the basolateral PM. VSVG is also a common coat protein for lentiviral vector expression systems used to introduce genetic material into in vitro systems or animal models, mainly because of its extremely broad tropism.{{cn|date=May 2023}}

The VSIV L protein is encoded by half the genome, and combines with the phosphoprotein to catalyze replication of the mRNA.

The VSIV M protein is encoded by an mRNA that is 831 nucleotides long and translates to a 229 amino acid-protein. The predicted M protein sequence does not contain any long hydrophobic or nonpolar domains that might promote membrane association. The protein is rich in basic amino acids and contains a highly basic amino terminal domain.{{cn|date=May 2023}}

The VSV N protein is required to initiate genome synthesis.{{cite journal | vauthors = Timm C, Gupta A, Yin J | title = Robust kinetics of an RNA virus: Transcription rates are set by genome levels | journal = Biotechnology and Bioengineering | volume = 112 | issue = 8 | pages = 1655–62 | date = August 2015 | pmid = 25726926 | pmc = 5653219 | doi = 10.1002/bit.25578 }}{{cite journal | vauthors = Davis NL, Wertz GW | title = Synthesis of vesicular stomatitis virus negative-strand RNA in vitro: dependence on viral protein synthesis | journal = Journal of Virology | volume = 41 | issue = 3 | pages = 821–32 | date = March 1982 | doi = 10.1128/JVI.41.3.821-832.1982 | pmid = 6284973 | pmc = 256819 | url = }}

The main sign in animals is oral disease appearing as mucosal vesicles and ulcers in the mouth, but also on the udder and around the coronary band. Animals may show systemic signs such as anorexia, lethargy and pyrexia (fever). Disease usually resolves within two weeks, and animals usually recover completely.

Cases of human infection with vesicular stomatitis virus have been described. Most of these cases have been among laboratory workers, veterinarians, and livestock handlers. In most cases, VSV infection has resulted in a short 3 to 5 day illness characterized by fever, headache, myalgia, weakness and occasionally vesicular lesions of the mouth.Quiroz E, Moreno N, Peralta PH, Tesh RB. A human case of encephalitis associated with vesicular stomatitis virus (Indiana serotype) infection. Am J Trop Med Hyg. 1988;39(3):312–314. doi:10.4269/ajtmh.1988.39.312 Serological testing is most commonly performed with an ELISA or complement fixation, and viral isolation can also be attempted.

No specific treatment is available, but some animals may require supportive fluids or antibiotics for secondary infections.

Control relies on biosecurity protocols, quarantine, isolation and disinfection to ensure the viral disease does not enter a country or herd.

In healthy human cells the virus cannot reproduce, likely because of the interferon response, which allows the cells to adequately respond to viral infection. The same cannot be said of interferon non-responsive cancer cells, a quality which allows VSIV to grow and lyse oncogenic cells preferentially.{{cite journal | vauthors = Stojdl DF, Lichty B, Knowles S, Marius R, Atkins H, Sonenberg N, Bell JC | title = Exploiting tumor-specific defects in the interferon pathway with a previously unknown oncolytic virus | journal = Nature Medicine | volume = 6 | issue = 7 | pages = 821–5 | date = July 2000 | pmid = 10888934 | doi = 10.1038/77558 | s2cid = 8492631 }}

Recently, attenuated VSIV with a mutation in its M protein has been found to have oncolytic properties. Research is ongoing, and has shown VSIV to reduce tumor size and spread in melanoma, lung cancer, colon cancer and certain brain tumors in laboratory models of cancer.{{cite journal | vauthors = Ozduman K, Wollmann G, Piepmeier JM, van den Pol AN | title = Systemic vesicular stomatitis virus selectively destroys multifocal glioma and metastatic carcinoma in brain | journal = The Journal of Neuroscience | volume = 28 | issue = 8 | pages = 1882–93 | date = February 2008 | pmid = 18287505 | pmc = 6671450 | doi = 10.1523/JNEUROSCI.4905-07.2008 }}

VSIV was modified to attack HIV-infected T-cells. The modified virus was called a "trojan horse" virus [https://web.archive.org/web/20131001232114/http://www.nih.gov/news/pr/sept97/niaid-04.htm NIH Press Release - Trojan Horse Virus Controls HIV Infection - 09/04/1997]

Recombinant VSIV has undergone phase 1 trials as a vaccine for Ebola virus.{{cite journal | vauthors = Agnandji ST, Huttner A, Zinser ME, Njuguna P, Dahlke C, Fernandes JF, Yerly S, Dayer JA, Kraehling V, Kasonta R, Adegnika AA, Altfeld M, Auderset F, Bache EB, Biedenkopf N, Borregaard S, Brosnahan JS, Burrow R, Combescure C, Desmeules J, Eickmann M, Fehling SK, Finckh A, Goncalves AR, Grobusch MP, Hooper J, Jambrecina A, Kabwende AL, Kaya G, Kimani D, Lell B, Lemaître B, Lohse AW, Massinga-Loembe M, Matthey A, Mordmüller B, Nolting A, Ogwang C, Ramharter M, Schmidt-Chanasit J, Schmiedel S, Silvera P, Stahl FR, Staines HM, Strecker T, Stubbe HC, Tsofa B, Zaki S, Fast P, Moorthy V, Kaiser L, Krishna S, Becker S, Kieny MP, Bejon P, Kremsner PG, Addo MM, Siegrist CA | display-authors = 6 | title = Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe | journal = The New England Journal of Medicine | volume = 374 | issue = 17 | pages = 1647–60 | date = April 2016 | pmid = 25830326 | pmc = 5490784 | doi = 10.1056/NEJMoa1502924 }}

Recombinant VSIV expressing the Ebola virus glycoprotein has undergone phase III trials in Africa as a vaccine for Ebola virus disease. The vaccine was shown to be 76-100% effective in preventing Ebola virus disease.{{cite journal | vauthors = Henao-Restrepo AM, Longini IM, Egger M, Dean NE, Edmunds WJ, Camacho A, Carroll MW, Doumbia M, Draguez B, Duraffour S, Enwere G, Grais R, Gunther S, Hossmann S, Kondé MK, Kone S, Kuisma E, Levine MM, Mandal S, Norheim G, Riveros X, Soumah A, Trelle S, Vicari AS, Watson CH, Kéïta S, Kieny MP, Røttingen JA | display-authors = 6 | title = Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial | journal = Lancet | volume = 386 | issue = 9996 | pages = 857–66 | date = August 2015 | pmid = 26248676 | doi = 10.1016/S0140-6736(15)61117-5 | hdl = 10144/575218 | s2cid = 40830730 | hdl-access = free }}{{cite journal | vauthors = Henao-Restrepo AM, Camacho A, Longini IM, Watson CH, Edmunds WJ, Egger M, Carroll MW, Dean NE, Diatta I, Doumbia M, Draguez B, Duraffour S, Enwere G, Grais R, Gunther S, Gsell PS, Hossmann S, Watle SV, Kondé MK, Kéïta S, Kone S, Kuisma E, Levine MM, Mandal S, Mauget T, Norheim G, Riveros X, Soumah A, Trelle S, Vicari AS, Røttingen JA, Kieny MP | display-authors = 6 | title = Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!) | journal = Lancet | volume = 389 | issue = 10068 | pages = 505–518 | date = February 2017 | pmid = 28017403 | pmc = 5364328 | doi = 10.1016/S0140-6736(16)32621-6 }} (see also rVSV-ZEBOV vaccine) In December 2019, Merck & Co.'s rVSV-ZEBOV vaccine Ervebo was approved by the Food and Drug Administration to treat individuals 18 and older.{{Cite web|last=Commissioner|first=Office of the|date=2020-03-24|title=First FDA-approved vaccine for the prevention of Ebola virus disease, marking a critical milestone in public health preparedness and response|url=https://www.fda.gov/news-events/press-announcements/first-fda-approved-vaccine-prevention-ebola-virus-disease-marking-critical-milestone-public-health|access-date=2021-10-20|website=FDA|language=en}}

Replication competent rVSV has also been created expressing proteins of Lassa fever and Marburg virus.{{cite journal | vauthors = Garbutt M, Liebscher R, Wahl-Jensen V, Jones S, Möller P, Wagner R, Volchkov V, Klenk HD, Feldmann H, Ströher U | display-authors = 6 | title = Properties of replication-competent vesicular stomatitis virus vectors expressing glycoproteins of filoviruses and arenaviruses | journal = Journal of Virology | volume = 78 | issue = 10 | pages = 5458–65 | date = May 2004 | pmid = 15113924 | pmc = 400370 | doi = 10.1128/jvi.78.10.5458-5465.2004 }}

The VSIV G protein is routinely used in biomedical research to pseudotype retroviral and lentiviral vectors, conferring the ability to transduce a broad range of mammalian cell types with genes of interest.{{cite journal | vauthors = Cronin J, Zhang XY, Reiser J | title = Altering the tropism of lentiviral vectors through pseudotyping | journal = Current Gene Therapy | volume = 5 | issue = 4 | pages = 387–98 | date = August 2005 | pmid = 16101513 | pmc = 1368960 | doi = 10.2174/1566523054546224 }}

The VSIV G protein has also been used in cytological studies of trafficking in the endomembrane system. Immunoelectron microscopy suggests that VSIV G protein moves from cis to trans Golgi bodies without being transported between them in vesicles, supporting the cisternal maturation model of Golgi trafficking.{{cite journal | vauthors = Mironov AA, Beznoussenko GV, Nicoziani P, Martella O, Trucco A, Kweon HS, Di Giandomenico D, Polishchuk RS, Fusella A, Lupetti P, Berger EG, Geerts WJ, Koster AJ, Burger KN, Luini A | display-authors = 6 | title = Small cargo proteins and large aggregates can traverse the Golgi by a common mechanism without leaving the lumen of cisternae | journal = The Journal of Cell Biology | volume = 155 | issue = 7 | pages = 1225–38 | date = December 2001 | pmid = 11756473 | pmc = 2199327 | doi = 10.1083/jcb.200108073 }}

VSV is often used to perform quantitative and computational studies on viral genome replication and transcription.{{cite journal | vauthors = Lim KI, Lang T, Lam V, Yin J | title = Model-based design of growth-attenuated viruses | journal = PLOS Computational Biology | volume = 2 | issue = 9 | pages = e116 | date = September 2006 | pmid = 16948530 | pmc = 1557587 | doi = 10.1371/journal.pcbi.0020116 | bibcode = 2006PLSCB...2..116L | doi-access = free }} Such studies help build a better understanding of viral behavior in the presence and absence of innate immune response.{{cn|date=May 2023}}

In 2020, a possible vaccine against COVID-19, the disease caused by SARS-CoV-2, was developed based on modified VSV. The modification involved replacing the VSV's surface protein genes with those for SARS-CoV-2's spike proteins.SciTechDaily: [https://scitechdaily.com/researchers-create-a-virus-that-mimics-sars-cov-2-the-covid-19-coronavirus-heres-why/ Researchers Created a Virus That Mimics SARS-CoV-2, the COVID-19 Coronavirus – Here’s Why]. Source: Washington University School of Medicine. August 19, 2020James Brett Case, Paul W. Rothlauf, Rita E. Chen, Zhuoming Liu, Haiyan Zhao, Arthur S. Kim, Louis-Marie Bloyet, Qiru Zeng, Stephen Tahan, Lindsay Droit, Ma. Xenia G. Ilagan, Michael A. Tartell, Gaya Amarasinghe, Jeffrey P. Henderson, Shane Miersch, Mart Ustav, Sachdev Sidhu, Herbert W. Virgin, David Wang, Siyuan Ding, Davide Corti, Elitza S. Theel, Daved H. Fremont, Michael S. Diamond and Sean P. J. Whelan: [https://www.sciencedirect.com/science/article/pii/S1931312820303620?via%3Dihub Neutralizing Antibody and Soluble ACE2 Inhibition of a Replication-Competent VSV-SARS-CoV-2 and a Clinical Isolate of SARS-CoV-2], Cell Host and Microbe, 1 July 2020, doi:10.1016/j.chom.2020.06.021

• Vesiculovirus matrix proteins
• Viral neuronal tracing
• rVSV-ZEBOV vaccine

{{Reflist|2}}

• [http://www.expasy.org/viralzone/all_by_species/21.html ViralZone: Vesiculovirus]
• [http://www.labonsite.com/background.php?id=3 Vesicular Stomatitis Virus] from The Lab-On-Site Project.
• [http://www.oie.int/fileadmin/Home/eng/Animal_Health_in_the_World/docs/pdf/Disease_cards/VESICULAR_STOMATITIS.pdf Disease card] on World Organisation for Animal Health

{{Viral diseases}}

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Category:Vesiculoviruses

de:Stomatitis vesicularis