''Indiana vesiculovirus'', formerly ''Vesicular stomatitis Indiana virus'' (VSIV or VSV) is a

virus A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Since Dmitri Ivanovsky's 1 ...

in the family ''

Rhabdoviridae ''Rhabdoviridae'' is a family of negative-strand RNA viruses in the order ''Mononegavirales''. Vertebrates (including mammals and humans), invertebrates, plants, fungi and protozoans serve as natural hosts. Diseases associated with member virus ...

''; the well-known ''

Rabies lyssavirus Rabies virus, scientific name ''Rabies lyssavirus'', is a neurotropic virus that causes rabies in humans and animals. Rabies transmission can occur through the saliva of animals and less commonly through contact with human saliva. ''Rabies lyss ...

'' belongs to the same family. VSIV can infect

insect Insects (from Latin ') are pancrustacean hexapod invertebrates of the class Insecta. They are the largest group within the arthropod phylum. Insects have a chitinous exoskeleton, a three-part body ( head, thorax and abdomen), three pairs ...

s, cattle, horses and pigs. It has particular importance to farmers in certain regions of the world where it infects cattle. This is because its clinical presentation is identical to the very important

foot and mouth disease Foot-and-mouth disease (FMD) or hoof-and-mouth disease (HMD) is an infectious and sometimes fatal viral disease that affects cloven-hoofed animals, including domestic and wild bovids. The virus causes a high fever lasting two to six days, followe ...

virus. reviewed and published by

WikiVet WikiVet is a wiki of veterinary content based on the MediaWiki platform. The website is a collaborative initiative between various veterinary schools, and its content covers the entire veterinary curriculum. WikiVet is part of the WikiVet Educatio ...

, accessed 12 October 2011. The virus is

zoonotic A zoonosis (; plural zoonoses) or zoonotic disease is an infectious disease of humans caused by a pathogen (an infectious agent, such as a bacterium, virus, parasite or prion) that has jumped from a non-human (usually a vertebrate) to a human. ...

and leads to a flu-like illness in infected humans. It is also a common laboratory virus used to study the properties of viruses in the family ''Rhabdoviridae'', as well as to study

viral evolution Viral evolution is a subfield of evolutionary biology and virology that is specifically concerned with the evolution of viruses. Viruses have short generation times, and many—in particular RNA viruses—have relatively high mutation rates (on the ...

Properties

''Indiana vesiculovirus'' is the prototypic member of the genus ''Vesiculovirus'' of the family ''Rhabdoviridae''. VSIV is an

arbovirus Arbovirus is an informal name for any virus that is transmitted by arthropod vectors. The term ''arbovirus'' is a portmanteau word (''ar''thropod-''bo''rne ''virus''). ''Tibovirus'' (''ti''ck-''bo''rne ''virus'') is sometimes used to more spe ...

, and its replication occurs in the cytoplasm. Natural VSIV infections encompass two steps,

cytolytic Cytolysis, or osmotic lysis, occurs when a cell bursts due to an osmotic imbalance that has caused excess water to diffuse into the cell. Water can enter the cell by diffusion through the cell membrane or through selective membrane channels ...

infections of mammalian hosts and transmission by insects. In insects, infections are noncytolytic persistent. One confirmed

vector Vector most often refers to: *Euclidean vector, a quantity with a magnitude and a direction *Vector (epidemiology), an agent that carries and transmits an infectious pathogen into another living organism Vector may also refer to: Mathematic ...

of the virus is the phlebotomine sand fly '' Lutzomyia shannoni''. The genome of VSIV is on a single molecule of negative-sense RNA that has 11,161 nucleotides in length, 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 Viral entry is the earliest stage of infection in the viral life cycle, as the virus comes into contact with the host cell (biology), cell and introduces viral material into the cell. The major steps involved in viral entry are shown below. Desp ...

. It mediates viral attachment to an

LDL Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall densit ...

receptor ( LDLR) or an LDLR family member present on the host cell. 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 Clathrin is a protein that plays a major role in the formation of coated vesicles. Clathrin was first isolated and named by Barbara Pearse in 1976. It forms a triskelion shape composed of three clathrin heavy chains and three light chains. Whe ...

-coated vesicles; virus-containing vesicles contain more clathrin and clathrin adaptor than conventional vesicles. Virus-containing vesicles recruit components of the

actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of over ...

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 Glycosylation is the reaction in which a carbohydrate (or ' glycan'), i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule (a glycosyl acceptor) in order to form a glycoconjugate. In biology (but not al ...

in the

endoplasmic reticulum The endoplasmic reticulum (ER) is, in essence, the transportation system of the eukaryotic cell, and has many other important functions such as protein folding. It is a type of organelle made up of two subunits – rough endoplasmic reticulum ( ...

(ER). It is translated into the rough ER where the Glc₃-

Man A man is an adult male human. Prior to adulthood, a male human is referred to as a boy (a male child or adolescent). Like most other male mammals, a man's genome usually inherits an X chromosome from the mother and a Y chromos ...

₉-

GlcNac ''N''-Acetylglucosamine (GlcNAc) is an amide derivative of the monosaccharide glucose. It is a secondary amide between glucosamine and acetic acid. It is significant in several biological systems. It is part of a biopolymer in the bacterial ...

₂ oligosaccharide is added by a

dolichol Dolichol refers to any of a group of long-chain mostly unsaturated organic compounds that are made up of varying numbers of isoprene units terminating in an α-saturated isoprenoid group, containing an alcohol functional group. Functions Dolich ...

-containing protein, to an NXS motif on VSIV G. Sugars are removed gradually as the protein travels to the

Golgi apparatus The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic cells. Part of the endomembrane system in the cytoplasm, it packages proteins into membrane-bound vesicles ins ...

, and it becomes resistant to

endoglycosidase H The enzyme endoglycosidase H () is an enzyme with systematic name ''glycopeptide-D-mannosyl-N4-(N-acetyl-D-glucosaminyl)2-asparagine 1,4-N-acetyl-beta-glucosaminohydrolase''. It is a highly specific endoglycosidase which cleaves asparagine-linked m ...

. 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 ''Lentivirus'' is a genus of retroviruses that cause chronic and deadly diseases characterized by long incubation periods, in humans and other mammalian species. The genus includes the human immunodeficiency virus (HIV), which causes AIDS. Lent ...

vector expression systems used to introduce genetic material into ''in vitro'' systems or animal models, mainly because of its extremely broad tropism. The VSIV L protein is encoded by half the genome, and combines with the

phosphoprotein A phosphoprotein is a protein that is posttranslationally modified by the attachment of either a single phosphate group, or a complex molecule such as 5'-phospho-DNA, through a phosphate group. The target amino acid is most often serine, threonin ...

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. The VSV N protein is required to initiate genome synthesis.

Vesicular stomatitis

Clinical signs and diagnosis

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, also referred to as pyrexia, is defined as having a temperature above the normal range due to an increase in the body's temperature set point. There is not a single agreed-upon upper limit for normal temperature with sources using val ...

(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 Myalgia (also called muscle pain and muscle ache in layman's terms) is the medical term for muscle pain. Myalgia is a symptom of many diseases. The most common cause of acute myalgia is the overuse of a muscle or group of muscles; another likel ...

, weakness and occasionally vesicular lesions of the mouth. Serological testing is most commonly performed with an

ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presence ...

complement fixation The complement fixation test is an immunological medical test that can be used to detect the presence of either specific antibody or specific antigen in a patient's serum, based on whether complement fixation occurs. It was widely used to diagnos ...

, and viral isolation can also be attempted.

Treatment and control

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

biosecurity Biosecurity refers to measures aimed at preventing the introduction and/or spread of harmful organisms (e.g. viruses, bacteria, etc.) to animals and plants in order to minimize the risk of transmission of infectious disease. In agriculture, thes ...

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

Medical applications

Oncolytic therapy

In healthy human cells the virus cannot reproduce, likely because of the

interferon Interferons (IFNs, ) are a group of signaling proteins made and released by host cells in response to the presence of several viruses. In a typical scenario, a virus-infected cell will release interferons causing nearby cells to heighten the ...

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. Recently, attenuated VSIV with a mutation in its M protein has been found to have

oncolytic An oncolytic virus is a virus that preferentially infects and kills cancer cells. As the infected cancer cells are destroyed by lysis#Oncolysis, oncolysis, they release new infectious virus particles or virus, virions to help destroy the remaining ...

properties. Research is ongoing, and has shown VSIV to reduce tumor size and spread in melanoma, lung cancer, colon cancer and certain

brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...

tumors in laboratory models of cancer.

Anti-HIV therapy

VSIV was modified to attack

HIV The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...

-infected T-cells. The modified virus was called a "trojan horse" viru

Ebola vaccine

Recombinant VSIV has undergone phase 1 trials as a

vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifie ...

for

Ebola virus ''Zaire ebolavirus'', more commonly known as Ebola virus (; EBOV), is one of six known species within the genus ''Ebolavirus''. Four of the six known ebolaviruses, including EBOV, cause a severe and often fatal hemorrhagic fever in humans and ot ...

. Recombinant VSIV expressing the

glycoprotein has undergone phase III trials in Africa as a vaccine for

Ebola virus disease Ebola, also known as Ebola virus disease (EVD) and Ebola hemorrhagic fever (EHF), is a viral hemorrhagic fever in humans and other primates, caused by ebolaviruses. Symptoms typically start anywhere between two days and three weeks after becom ...

. The vaccine was shown to be 76-100% effective in preventing Ebola virus disease. (see also

rVSV-ZEBOV vaccine Recombinant vesicular stomatitis virus–Zaire Ebola virus (rVSV-ZEBOV), also known as Ebola Zaire vaccine live and sold under the brand name Ervebo, is an Ebola vaccine for adults that prevents Ebola caused by the Zaire ebolavirus. When used ...

) In December 2019, Merck & Co.'s

Ervebo was approved by the

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

to treat individuals 18 and older.

Other Uses

Replication competent rVSV has also been created expressing proteins of

Lassa fever Lassa fever, also known as Lassa hemorrhagic fever (LHF), is a type of viral hemorrhagic fever caused by the Lassa virus. Many of those infected by the virus do not develop symptoms. When symptoms occur they typically include fever, weakness, h ...

and

Marburg virus Marburg virus (MARV) is a hemorrhagic fever virus of the ''Filoviridae'' family of viruses and a member of the species '' Marburg marburgvirus'', genus ''Marburgvirus''. It causes Marburg virus disease in primates, a form of viral hemorrhagic f ...

Other applications

The VSIV G protein is routinely used in biomedical research to

pseudotype Pseudotyping is the process of producing viruses or viral vectors in combination with foreign viral envelope proteins. The result is a pseudotyped virus particle, also called a pseudovirus. With this method, the foreign viral envelope proteins can ...

retroviral and lentiviral vectors, conferring the ability to transduce a broad range of mammalian cell types with genes of interest. The VSIV G protein has also been used in cytological studies of trafficking in the

endomembrane system The endomembrane system is composed of the different membranes (endomembranes) that are suspended in the cytoplasm within a eukaryotic cell. These membranes divide the cell into functional and structural compartments, or organelles. In eukaryotes ...

. 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. VSV is often used to perform quantitative and computational studies on viral genome replication and transcription. Such studies help build a better understanding of viral behavior in the presence and absence of

innate immune response The innate, or nonspecific, immune system is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the ...

. In 2020, a possible vaccine against

COVID-19 Coronavirus disease 2019 (COVID-19) is a contagious disease caused by a virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was COVID-19 pandemic in Hubei, identified in Wuhan, China, in December ...

, the disease caused by

SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) is a strain of coronavirus that causes COVID-19 (coronavirus disease 2019), the respiratory illness responsible for the ongoing COVID-19 pandemic. The virus previously had a ...

, 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.James 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
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

References

External links

ViralZone: Vesiculovirus

Vesicular Stomatitis Virus
from The Lab-On-Site Project.
Disease card
on

World Organisation for Animal Health The World Organisation for Animal Health (WOAH), formerly the (OIE), is an intergovernmental organization coordinating, supporting and promoting animal disease control. Mission and status The main objective of the WOAH is to control epizoo ...

{{DEFAULTSORT:Vesicular Stomatitis Virus Vesiculoviruses de:Stomatitis vesicularis