# Betül Türkel - Rhabdoviruses
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The family Rhabdoviridae consists of more than 100 single-stranded, negative-sense, nonsegmented viruses that infect a wide variety of hosts, including vertebrates, invertebrates, and plants. Common to all members of the family is a distinctive rod- or bullet-shaped morphology.
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Source: https://viralzone.expasy.org/2?outline=all_by_species
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**GENES AND PROTEINS**
Five to nine genes, transcribed in series from the 3' end of the genome by viral RNA polymerase.
Most genes produce a single mRNA and a single protein. Most proteins are packaged in the virion.
Rhabdoviruses:
* Nucleocapsid protein (N)
* RNA polymerase cofactor and accessory proteins (P/C/V) Matrix protein (M)
* Fusion protein (F)
* Hemagglutinin/neuraminidase, or envelope glycoprotein (H, HN, or G)
* RNA polymerase (L)
**DISEASES**
**Rhabdoviruses:** rabies (fatal encephalitis in humans), trans- mitted by bites of infected animals; vesicular stomatitis virus in cattle. Numerous insect and plant diseases.
Source: Acheson, Nicholas H. Fundamentals of molecular virology. No. Ed. 2. John Wiley & Sons, Inc, 2011.
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**Classification of Rhabdoviruses**
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Rhabdoviruses are composed of two genera, in which **Vesicular Somatitis Virus** is the prototype of vesiculovirus genus, and **Rabies Virus** is the prototype of lyssavirus genus.
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**Structure of Rabies virus**
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* rod- or bullet-shaped
* single-stranded,
* negative-sense,
* unsegmented,
* enveloped RNA virus
* virus genome encodes five proteins.
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Source: Rupprecht CE. Rhabdoviruses: Rabies Virus. In: Baron S, editor. Medical Microbiology. 4th edition. Galveston (TX): University of Texas Medical Branch at Galveston; 1996. Chapter 61. Available from: https://www.ncbi.nlm.nih.gov/books/NBK8618/
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**Structure of vesicular stomatitis virus (VSV) particle**
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**RNA genome structure of VSV**
Five VSV genes (ORFs) are distinctly colored. Note that the 50 end of negative-strand RNA genome is positioned to the right. IGs (ie, noncoding region) positioned between coding regions are denoted by brackets. The viral mRNAs are capped at the 50 end and are polyadenylated at the 30 end. (1) and (2) denotes the polarity of the RNA.
Negative-stranded RNA linear genome, about 11-15 kb in size. Varicosavirus genomes consists in two segments. Encodes for 5 to six proteins.
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## THE LIFE CYCLE OF VSV
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The life cycle of VSV is confined to the cytoplasm.
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**Entry:** VSV particles enter the cell via recognition of phosphatidylserine on the plasma membrane. It is notable that a phospholipid molecule, instead of glycoprotein, acts as an entry receptor. Upon entry, the virus particle is located inside the endosome. Uncoating of the virus particles occurs in a manner coupled with cytoplasmic trafficking. The viral nucleocapsid penetrates to the cytoplasm via membrane fusion between the endosome and the viral envelope. The membrane fusion is triggered by the lower pH of the endosome, which induces the exposure of the hydrophobic region of G protein.
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**RNA Synthesis:** L/P protein complex associated with the nucleocapsid serves as RdRp for the viral RNA synthesis. Two positive-strand RNAs are transcribed from the negative-strand RNA genome: the subgenomic mRNAs and the genome-length RNA. The mRNA synthesis is referred to as “transcription,” while the genome-length RNA synthesis is referred to as “RNA replication.” Importantly, the nucleocapsid or ribonucleoprotein complex (RNP7), in which the RNA molecule is completely encircled by numerous N proteins, serves as the template. Note that the usage of the RNP complex as a template, instead of a naked RNA, is the hallmark of all NSVs.
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**Polyadenylation and reinitiation of VSV mRNA transcription.** The poly (A) tail of mRNA is synthesized by recopying a short run of U sequences located at the end of the coding region. The polyadenylation continues until over 200 A nucleotides are added by stuttering. It is believed that the longer poly (A) tail triggers not only transcription termination but also transcription reinitiation of the downstream gene. IGs (ie, NA dinucleotides, which is highlighted by bold face) are located between the short runs of U and the first nucleotide of the down- stream gene.
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**REPLICATION**
Cytoplasmic
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1. Attachement of the viral G glycoproteins to host receptors mediates Clathrin-mediated endocytosis of the virus into the host cell.
2. Fusion of virus membrane with the vesicle membrane; ribonucleocapsid is released into the cytoplasm.
3. Sequential transcription , viral mRNAs are capped and polyadenylated by polymerase stuttering in the cytoplasm.
4. Replication presumably starts when enough nucleoprotein is present to encapsidate neo-synthetized antigenomes and genomes.
5. The ribonucleocapsid binds to the matrix protein and buds via the host ESCRT complexes occurs at the plasma membrane, releasing new virions.
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Source: https://viralzone.expasy.org/2?outline=all_by_species
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Here is a video about Rhabdoviridae family.
{%youtube OvRxDQdAtGc%}
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Vesicular stomatitis virus (VSV) is a highly cytopathic virus being developed as a vaccine vector due to its ability to induce strong protective T cell and antibody responses after a single dose. However, little is known regarding the mechanisms underlying the potent immune responses elicited by VSV.
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Rabies virus, a human rhabdovirus, had been the focus of attention during the 19th century in Europe, as it causes a fatal transmissible disease. In fact, Louis Pasteur (1822-1895) studied rabies virus, even before the official discovery of “virus” as a submicrobial agent. He eventually developed a postexposure vaccine for the treatment of rabies infected individuals. On the other hand, VSV has been an extensively studied rhabdovirus, although VSV is not a significant human pathogen. Accumulated knowledge on VSV is now paying off by the recent discovery of the oncolytic activity of VSV that can be explored for cancer therapy. It is hoped that further exploitation of the oncolytic activity of VSV could lead to a cure for at least some types of cancer.
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**SUMMARY**
* **Rhabdovirus:** Rhabdoviruses are found in invertebrates as well as in vertebrate, ranging from mosquitoes to cattle. VSV is a prototype of animal rhabdovirus.
* **Human rhabdovirus:** Rabies virus represents a prototype of human rhabdovirus. Rabies virus causes fatal encephalo- myelitis in human.
* **VSV particle:** It is an enveloped virus, which contains the nucleocapsid of a helical symmetry inside. L/P protein complex (RdRp) is encapsidated inside the virion.
* **VSV genome:** It is a negative-strand RNA with 11 kb in length. Its 50 terminus is not capped, and its 30 terminus is not polyadenylated.
* **VSV genome replication:** vRNP (ie, nucleocapsid), instead of a naked RNA, serves as the template for the RNA synthesis. The N protein level regulates the transit from transcription to the genome replication.
* **Host effect of VSV:** VSV infection leads to host shut-off and cell lysis.
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