Рабдовирусы: структура, геном и жизненный цикл

Family of viruses in the order Mononegavirales

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 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 40 genera, most assigned to three subfamilies.

The individual virus particles (virions) of rhabdoviruses are composed of RNA, protein, carbohydrate and lipid. 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. Every rhabdoviruses encode these five proteins in their genomes. In addition to these proteins, many rhabdoviruses encode one or more proteins. In addition to the functions about virus assembly, morphogenesis and budding off enveloped from the host plasma membrane, additional functions such as the regulation of RNA synthesis, affecting the balance of replication and transcription products was found, making reverse genetics experiments with rabies virus, a member of the family Rhabdoviridae. The large (L) protein has several enzymatic functions in viral RNA synthesis and processing. The L gene encodes this L protein, which contains multiple domains. In addition to RNA synthesis, it is thought to be involved in methyl capping and polyadenylation activity. Rhabdoviruses that infect vertebrates (especially mammals and fishes), plants, and insects are usually bullet shaped. However, in contrast to paramyxoviruses, rhabdoviruses do not have hemagglutinating and neuraminidase activities. The rhabdovirus matrix (M) protein is very small (~20–25 kDa) however 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. The L protein has a lot of enzymatic activity such as RNA replication, capping mRNAs phosphorylation of P. L protein gives feature in about replication in cytoplasm. During their synthesis the mRNAs are processed to introduce a 5' cap and a 3’ polyadenylated tail to each of the molecules. This structure is homologous to cellular mRNAs and can thus be translated by cellular ribosomes to produce both structural and non structural proteins. Genomic replication requires a source of newly synthesized N protein to encapsidate the RNA. This occurs during its synthesis and results in the production of a full length anti genomic copy. This in turn is used to produce more negative sense genomic RNA. The viral polymerase is required for this process, but how the polymerase engages in both mRNA synthesis and genomic replication is not well understood. Replication characteristically occurs in an inclusion body within the cytoplasm, from where they bud through various cytoplasmic membranes and the outer membrane of the cell. This process results in the acquisition of the M + G proteins, responsible for the characteristic bullet shaped morphology of the virus.

These viruses fall into four groups based on the RNA polymerase gene. The basal clade appears to be novirhabdoviruses, which infect fish. Cytorhabdoviruses and the nucleorhabdoviruses, which infect plants, are sister clades. Lyssaviruses form a clade of their own which is more closely related to the land vertebrate and insect clades than to the plant viruses. The remaining viruses form a number of highly branched clades and infect arthropods and land vertebrates. A 2015 analysis of 99 species of animal rhabdoviruses found that they fell into 17 taxonomic groupings, eight – Lyssavirus, Vesiculovirus, Perhabdovirus, Sigmavirus, Ephemerovirus, Tibrovirus, Tupavirus and Sprivivirus – which were previously recognized. The authors proposed seven new taxa on the basis of their findings: "Almendravirus", "Bahiavirus", "Curiovirus", "Hapavirus", "Ledantevirus", "Sawgravirus" and "Sripuvirus". Seven species did not group with the others suggesting the need for additional taxa.

An unofficial supergroup – "Dimarhabdovirus" – refers to the genera Ephemerovirus and Vesiculovirus. A number of other viruses that have not been classified into genera also belong to this taxon. This supergroup contains the genera with species that replicate in both vertebrate and invertebrate hosts and have biological cycles that involve transmission by haematophagous dipterans (bloodsucking flies).

The prototypical and best studied rhabdovirus is vesicular stomatitis Indiana virus. It is a preferred model system to study the biology of rhabdoviruses, and mononegaviruses in general. The mammalian disease rabies is caused by lyssaviruses, of which several have been identified. Rhabdoviruses are important pathogens of animals and plants. Rhabdoviruses are transmitted to hosts by arthropods, such as aphids, planthoppers, leafhoppers, black flies, sandflies, and mosquitoes. In September 2012, researchers writing in the journal PLOS Pathogens described a novel species of rhabdovirus, called Bas Congo virus (BASV), which was discovered in a blood sample from a patient who survived an illness that resembled hemorrhagic fever. In 2015 two novel rhabdoviruses, Ekpoma virus 1 and Ekpoma virus 2, were discovered in samples of blood from two healthy women in southwestern Nigeria. Ekpoma virus 1 and Ekpoma virus 2 appear to replicate well in humans (viral load ranged from ~45,000 ~4.5 million RNA copies/mL plasma) but did not cause any observable symptoms of disease. Exposure to Ekpoma virus 2 appears to be widespread in certain parts of Nigeria where seroprevalence rates are close to 50%.