Vesicular stomatitis virus
Encyclopedia
Vesicular stomatitis Indiana virus (VSIV) (often still referred to as VSV) is a virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...

 in the family Rhabdoviridae
Rhabdoviridae
Rhabdoviruses are viruses belonging to the family Rhabdoviridae, which is in the order Mononegavirales. The name is derived from the Greek rhabdos meaning rod referring to the shape of the viral particles. Rhabdoviruses infect a broad range of hosts throughout the animal and plant kingdoms...

; the well-known Rabies virus
Rabies virus
The rabies virus is neurotropic virus that causes fatal disease in human and animals. Rabies transmission can occur through the saliva of animals....

 belongs to the same family. VSIV can infect insect
Insect
Insects are a class of living creatures within the arthropods that have a chitinous exoskeleton, a three-part body , three pairs of jointed legs, compound eyes, and two antennae...

s, cattle, horses, pigs and humans. It has particular importance to farmers in certain regions of the world where it can infect cattle. This is because its clinical presentation is identical to the very important Foot and Mouth Disease virus.


The virus is zoonotic 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.

Properties

VSIV is an arbovirus
Arbovirus
Arbovirus is a term used to refer to a group of viruses that are transmitted by arthropod vectors. The word arbovirus is an acronym . Some arboviruses are able to cause emergent disease.-Transmission:...

: natural VSIV infections encompass two steps, cytolytic infections of mammalian hosts and transmission by insects. In insects, infections are non-cytolytic persistent.

Vesicular stomatitis Indiana virus (VSIV) is the prototypic member of the genus Vesiculovirus of the family Rhabdoviridae. The genome of the virus is a single molecule of negative-sense RNA that encodes five major proteins: G protein (G), large protein (L), phosphoprotein, matrix protein (M) and nucleoprotein.

The VSIV G protein enables viral entry
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 and introduces viral material into the cell. The major steps involved in viral entry are shown below. Despite the variation among viruses, the generalities are quite similar...

. It mediates virus attachment to the host cell, where it is endocytosed
Endocytosis
Endocytosis is a process by which cells absorb molecules by engulfing them. It is used by all cells of the body because most substances important to them are large polar molecules that cannot pass through the hydrophobic plasma or cell membrane...

. 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.

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.

After infection, the VSIV G gene is expressed and is commonly studied as a model for N-linked glycosylation
Glycosylation
Glycosylation is the reaction in which a carbohydrate, i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule . In biology glycosylation refers to the enzymatic process that attaches glycans to proteins, lipids, or other organic molecules...

 in the endoplasmic reticulum
Endoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...

. It is translated into the rough ER where the Glc
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

3-Man
Mannose
Mannose is a sugar monomer of the aldohexose series of carbohydrates. Mannose is a C-2 epimer of glucose. It is not part of human metabolism, but is a component of microbial cell walls, and is therefore a target of the immune system and also of antibiotics....

9-GlcNac2 oligosaccharide is added by a dolichol
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:...

-containing protein, to an NXS motif on VSIV G. Sugars are removed gradually as the protein travels to the Golgi apparatus
Golgi apparatus
The Golgi apparatus is an organelle found in most eukaryotic cells. It was identified in 1898 by the Italian physician Camillo Golgi, after whom the Golgi apparatus is named....

, and it becomes resistant to endoglycosidase H
Endoglycosidase H
The enzyme Endoglycosidase H The enzyme Endoglycosidase H The enzyme Endoglycosidase H (Endo-β-N-acetylglucosaminidase H, is a highly specific endoglycosidase which cleaves asparagine-linked mannose rich oligosaccharides, but not highly processed complex oligosaccharides from glycoproteins...

.

VSIV G does not follow the same path as most vesicles because transport of the G protein from the endoplasmic reticulum to the plasma membrane is interrupted by incubation at 15°C. Under this condition, the molecules accumulate in both the endoplasmic reticulum (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). When synthesized in polarized epithelial cells, the envelope glycoproteins hemagglutinin of VSIV G are targeted to the apical and basolateral plasma membranes. 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.

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. Disease usually resolves within 2 weeks and animals usually recover completely.

Serological testing is most commonly performed with en ELISA
ELISA
Enzyme-linked immunosorbent assay , is a popular format of a "wet-lab" type analytic biochemistry assay that uses one sub-type of heterogeneous, solid-phase enzyme immunoassay to detect the presence of a substance in a liquid sample."Wet lab" analytic biochemistry assays involves detection of an...

 or complement fixation 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
Biosecurity is a set of preventive measures designed to reduce the risk of transmission of infectious diseases, quarantined pests, invasive alien species, living modified organisms...

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

Oncolytic therapy

VSIV has oncolytic activity, leading to preferential killing of infected tumor cells. Recently, attenuated VSIV with a mutation in its M protein has been found to have oncolytic
Oncolytic virus
An oncolytic virus is a virus that preferentially infects and lyses cancer cells; these have obvious functions for cancer therapy, both by direct destruction of the tumour cells, and, if modified, as vectors enabling genes expressing anticancer proteins to be delivered specifically to the tumor...

 properties. Research is ongoing, and has shown VSV to reduce tumor size and spread in melanoma, lung cancer, colon cancer and certain brain tumors in laboratory models of cancer.

Other applications

The VSIV G protein is commonly used in biomedical research to pseudotype
Pseudotyping
Pseudotyping is the process of producing viruses or viral vectors in combination with foreign viral envelope proteins. The result is a pseudotyped virus particle.. With this method, the foreign viral envelope proteins can be used to alter host tropism or an increased/decreased stability of the...

 retroviral and lentiviral vectors
Viral vector
Viral vectors are a tool commonly used by molecular biologists to deliver genetic material into cells. This process can be performed inside a living organism or in cell culture . Viruses have evolved specialized molecular mechanisms to efficiently transport their genomes inside the cells they infect...

, conveying the ability to transduce a broad range of mammalian cell types with genes of interest.

External links

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