| Indiana vesiculovirus | |
|---|---|
_EM_18_lores.jpg) | |
| TEMmicrograph ofIndiana vesiculovirus particles | |
Virus classification | |
| (unranked): | Virus |
| Realm: | Riboviria |
| Kingdom: | Orthornavirae |
| Phylum: | Negarnaviricota |
| Class: | Monjiviricetes |
| Order: | Mononegavirales |
| Family: | Rhabdoviridae |
| Genus: | Vesiculovirus |
| Species: | Indiana vesiculovirus |
| Synonyms[1] | |
| |
Indiana vesiculovirus, formerlyVesicular stomatitis Indiana virus (VSIV orVSV) is avirus in the familyRhabdoviridae; the well-knownRabies lyssavirus belongs to the same family. VSIV can infectinsects, 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 importantfoot and mouth disease virus.[2]
The virus iszoonotic 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 familyRhabdoviridae, as well as to studyviral evolution.[3]
Indiana vesiculovirus is the prototypic member of the genusVesiculovirus of the familyRhabdoviridae. VSIV is anarbovirus, 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 confirmedvector of the virus is thephlebotomine sand flyLutzomyia shannoni.[4] The genome of VSIV is on a single molecule of negative-sense RNA that has 11,161 nucleotides in length,[5] 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, enablesviral entry. It mediates viral attachment to anLDL receptor (LDLR) or an LDLR family member present on the host cell.[6] Following binding, the VSIV-LDLR complex is rapidlyendocytosed. It then mediates fusion of the viral envelope with the endosomal membrane. VSIV enters the cell through partiallyclathrin-coated vesicles; virus-containing vesicles contain more clathrin and clathrin adaptor than conventional vesicles. Virus-containing vesicles recruit components of theactin 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 forN-linkedglycosylation in theendoplasmic reticulum (ER). It is translated into the rough ER where theGlc3-Man9-GlcNac2 oligosaccharide is added by adolichol-containing protein, to an NXSmotif on VSIV G. Sugars are removed gradually as the protein travels to theGolgi apparatus, and it becomes resistant toendoglycosidase H.[7] When synthesized in polarized epithelial cells, the envelope glycoprotein VSV G is targeted to the basolateral PM. VSVG is also a common coat protein forlentiviral vector expression systems used to introduce genetic material intoin vitro systems or animal models, mainly because of its extremely broad tropism.[citation needed]
The VSIV L protein is encoded by half the genome, and combines with thephosphoprotein 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.[citation needed]
The VSV N protein is required to initiate genome synthesis.[8][9]
The main sign in animals is oral disease appearing as mucosal vesicles and ulcers in the mouth, but also on the udder and around thecoronary band. Animals may show systemic signs such as anorexia, lethargy andpyrexia (fever). Disease usually resolves within two weeks, and animals usually recover completely.[2]
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.[10] Serological testing is most commonly performed with anELISA orcomplement fixation, and viral isolation can also be attempted.[2]
No specific treatment is available, but some animals may require supportive fluids or antibiotics for secondary infections.[2]
Control relies onbiosecurity protocols, quarantine, isolation and disinfection to ensure the viral disease does not enter a country or herd.[2]
In healthy human cells the virus cannot reproduce, likely because of theinterferon 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.[11]
Recently, attenuated VSIV with a mutation in itsM protein has been found to haveoncolytic properties. Research is ongoing, and has shown VSIV to reduce tumor size and spread in melanoma, lung cancer, colon cancer and certainbrain tumors in laboratory models of cancer.[12]
VSIV was modified to attackHIV-infected T-cells. The modified virus was called a "trojan horse" virusNIH Press Release - Trojan Horse Virus Controls HIV Infection - 09/04/1997
Recombinant VSIV has undergone phase 1 trials as avaccine forEbola virus.[13]
Recombinant VSIV expressing theEbola virus glycoprotein has undergone phase III trials in Africa as a vaccine forEbola virus disease. The vaccine was shown to be 76-100% effective in preventing Ebola virus disease.[14][15] (see alsorVSV-ZEBOV vaccine) In December 2019,Merck & Co.'srVSV-ZEBOV vaccine Ervebo was approved by theFood and Drug Administration to treat individuals 18 and older.[16]
Replication competent rVSV has also been created expressing proteins ofLassa fever andMarburg virus.[17]
The VSIV G protein is routinely used in biomedical research topseudotype retroviral and lentiviralvectors, conferring the ability to transduce a broad range of mammalian cell types with genes of interest.[18]
The VSIV G protein has also been used in cytological studies of trafficking in theendomembrane system. Immunoelectron microscopy suggests that VSIV G protein moves fromcis totrans Golgi bodies without being transported between them in vesicles, supporting thecisternal maturation model of Golgi trafficking.[19]
VSV is often used to perform quantitative and computational studies on viral genome replication and transcription.[8][20] Such studies help build a better understanding of viral behavior in the presence and absence ofinnate immune response.[citation needed]
In 2020, a possible vaccine againstCOVID-19, the disease caused bySARS-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.[21][22]