Rhabdoviridae is a family of negative-strand RNA viruses in the order Mononegavirales. Vertebrates (including mammals), invertebrates, plants, fungi, and protozoans serve as natural hosts. Diseases associated with member viruses include rabies encephalitis caused by the rabies virus, and flu-like symptoms in humans caused by vesiculoviruses. The name is derived from Ancient Greek rhabdos, meaning rod, referring to the shape of the viral particles. The family has 64 genera, most of which are assigned to four subfamilies.
Structure The individual virus particles (virions) of rhabdoviruses are composed of RNA, protein, carbohydrate, and lipids. They have complex bacilliform or bullet-like shapes. All these viruses have structural similarities and have been classified as a single family. The virions are about 75 nm wide and 180 nm long. Rhabdoviruses are enveloped and have helical nucleocapsids and their genomes are linear, around 11–15 kb in length. Rhabdoviruses carry their genetic material in the form of negative-sense single-stranded RNA. They typically carry genes for five proteins: large protein (L), glycoprotein (G), nucleoprotein (N), phosphoprotein (P), and matrix protein (M). The sequence of these protein genes from the 3 'end to the 5' end in the genome is N–P–M–G–L. Every rhabdoviruses encodes these five proteins in their genomes. In addition to these proteins, many rhabdoviruses encode one or more proteins. The first four genes encode major structural proteins that participate in the structure of the virion envelope. The matrix protein (M) constitutes a layer between the virion envelope and the nucleocapsid core of the rhabdovirus. In addition to its functions in virus assembly, morphogenesis, and budding off enveloped from the host plasma membrane, additional functions such as regulation of RNA synthesis and establishing balance between replication and transcription products, were found for M protein through reverse genetics experiments with rabies virus, a member of the family Rhabdoviridae. The large (L) protein has contains multiple domains and several enzymatic functions in viral RNA synthesis and processing. In addition to RNA synthesis, it is thought to be involved in methyl capping and polyadenylation activity. The multifunctional P protein is encoded by the P gene. P protein plays important and multiple roles during transcription and replication of the RNA genome. P protein acts as a non-catalytic cofactor of large protein polymerase. It is binding to N and L protein. P protein has two independent binding regions. By forming N-P complexes, it can keep the N protein in the form suitable for specific encapsulation. P protein interferes with the host's innate immune system through inhibition of the activities of interferon regulatory factor 3 (IRF3) and signal transducer and activator of transcription 1 (STAT1), thus eliminating the cellular type 1 interferon pathway. P protein also acts as an antagonist against antiviral PML function. In contrast to paramyxoviruses, rhabdoviruses do not have hemagglutinating and neuraminidase activities.
Transcription
Transcriptase of rhabdovirus is composed of 1 L and 3 P proteins. Transcriptase components are always present in the complete virion to permit rhabdoviruses to begin transcription immediately after entry. The rhabdovirus transcriptase proceeds in a 3' to 5' direction on the genome and the transcription terminates randomly at the end of protein sequences. For example, if a transcription finishes at the end of M sequence; leader RNA and N, P, and M mRNAs are formed separately from each other. mRNAs also accumulate according to the order of protein sequences on the genome, solving the logistics problem in the cell. For example, N protein is necessary in high quantities for the virus, as it coats the outside of the replicated genomes completely. Since the N protein sequence is located at the beginning of the genome (3' end) after the leader RNA sequence, mRNAs for N protein can always be produced and accumulate in high amounts with every termination of transcription. After the transcription processes, all of the mRNAs are capped at the 5' end and polyadenylated at the 3' end by L protein. This transcription mechanism thus provides mRNAs according to the need of the viruses.
Translation The virus proteins are translated on free ribosomes but G protein is translated by the rough endoplasmic reticulum. This means G protein has a signal peptide on its mRNA's starting codes. Phosphoproteins (P) and glycoprotein (G) undergo post-translational modification. Trimers of P protein are formed after phosphorylation by kinase activity of L protein. The G protein is glycosylated in the rough endoplasmic reticulum and the Golgi complex.
Replication
Viral replication is cytoplasmic. The replication cycle is the same for most rhabdoviruses. All components required for early transcription and the nucleocapsid are released to the cytoplasm of the infected cell after the first steps of binding, penetration, and uncoating take place. Entry into the host cell is achieved by attachment of the viral G glycoproteins to host receptors, which mediates clathrin-mediated endocytosis. Replication follows the negative-stranded RNA virus replication model. Negative-stranded RNA virus transcription, using polymerase stuttering, is the method of transcription. The virus exits the host cell by budding and tubule-guided viral movement. Replication of many rhabdoviruses occurs in the cytoplasm, although several of the plant infecting viruses replicate in the nucleus. The rhabdovirus matrix (M) protein is very small (~20–25 kDa), however it plays a number of important roles during the replication cycle of the virus. These proteins of rhabdoviruses constitute major structural components of the virus and they are multifunctional proteins and required for virus maturation and viral budding process that also regulate the balance of virus RNA synthesis by shifting synthesis from transcription to replication. In order for replication, both the L and P protein must be expressed to regulate transcription. Phosphoprotein (P) also plays a crucial role during replication, as N-P complexes, rather than N alone, are necessary for appropriate and selective encapsidation of viral RNA. Therefore, replication is not possible after infection until the primary transcription and translation produce enough N protein.
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