Lyssavirus

''Lyssavirus'' (from the Greek ''lyssa'' "rage, fury, rabies" and the Latin '' vīrus'') is a genus of RNA viruses in the family ''Rhabdoviridae'', order '' Mononegavirales''. Mammals, including humans, can serve as natural hosts. The genus ''Lyssavirus'' includes the causative agent (rabies virus) of rabies.

Taxonomy

The genus contains the following species, listed by scientific name and followed by the exemplar virus of the species:

* ''Lyssavirus aravan'', Aravan virus
* ''Lyssavirus australis'', Australian bat lyssavirus
* ''Lyssavirus bokeloh'', Bokeloh bat lyssavirus
* ''Lyssavirus caucasicus'', West Caucasian bat virus
* ''Lyssavirus duvenhage'', Duvenhage virus
* ''Lyssavirus formosa'', Taiwan bat lyssavirus
* ''Lyssavirus gannoruwa'', Gannoruwa bat lyssavirus
* ''Lyssavirus hamburg'', European bat lyssavirus 1
* ''Lyssavirus helsinki'', European bat lyssavirus 2
* ''Lyssavirus ikoma'', Ikoma lyssavirus
* ''Lyssavirus irkut'', Irkut virus
* ''Lyssavirus khujand'', Khujand virus
* ''Lyssavirus kotalahti'', Kotalahti bat lyssavirus
* ''Lyssavirus lagos'', Lagos bat virus
* ''Lyssavirus lleida'', Lleida bat lyssavirus
* ''Lyssavirus mokola'', Mokola virus
* ''Lyssavirus rabies'', Rabies virus
* ''Lyssavirus shimoni'', Shimoni bat virus

Virology

Structure

Lyssavirions are enveloped, with bullet shaped geometries. These virions are about 75 nm wide and 180 nm long. Lyssavirions have helical symmetry, so their infectious particles are approximately cylindrical in shape. This is typical of plant-infecting viruses. Virions of human-infecting viruses more commonly have cubic symmetry and take shapes approximating regular polyhedra.

The structure consists of a spiked outer envelope, a middle region consisting of matrix protein M, and an inner ribonucleocapsid complex region, consisting of the genome associated with other proteins.

Genome

Lyssavirus genomes consist of a negative-sense, single-stranded RNA molecule that encodes five viral proteins: polymerase L, matrix protein M, phosphoprotein P, nucleoprotein N, and glycoprotein G. Genomes are linear, around 11kb in length.

Based on recent phylogenetic evidence, lyssaviruses have been categorized into seven major species. In addition, five more species have recently been discovered: West Caucasian bat virus, Aravan virus, Khujand virus, Irkut virus and Shimoni bat virus. The lyssavirus genus can be divided into four phylogroups based upon DNA sequence homology. Phylogroup I includes viruses, such as Rabies virus, Duvenhage virus, European bat lyssavirus types 1 and 2, Australian bat lyssavirus, Khujand virus, Bokeloh bat lyssavirus, Irkut virus, and Aravan virus. Phylogroup II contains Lagos bat virus, Mokola virus, and Shimoni bat virus. West Caucasian bat lyssavirus is the only virus that is a part of phylogroup III. Ikoma lyssavirus and Lleida bat lyssavirus are examples in phylogroup IV. West Caucasian bat lyssavirus was classified within its own phylogroup because it is the most divergent lyssavirus that has been discovered.

Evolution

Phylogenetic studies suggest that the original hosts of these viruses were bats. However, the recent discovery of lyssavirus sequences from amphibians and reptiles challenges the mammalian origin of lyssaviruses. The greater antigenic diversity of lyssaviruses from Africa has led to the assumption that Africa was the origin of these viruses. An examination of 153 viruses collected between 1956 and 2015 from various geographic locations has instead suggested a Palearctic origin (85% likelihood) for these viruses. Date estimates (95% likelihood) for the most recent common ancestor were very broad – between 3,995 and 166,820 years before present – which suggests there is further work to be done in this area. Although bats evolved in the Palearctic, their origins antedate that of the lyssaviruses by millions of years, which argues against their co-speciation. The evolution rate in the N gene in the Africa 2 lineage has been estimated to be 3.75×10⁻³ substitutions per site per year. This rate is similar to that of other RNA viruses.

Life cycle

Viral replication is cytoplasmic. 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 by tubule-guided viral movement.
Wild mammals, especially bats and certain carnivores, serve as natural hosts. Transmission routes are typically via bite wounds.

Testing

As of 2018 the direct fluorescent antibody (DFA) test is still the gold standard to detect lyssavirus infection. Since the new millennium reverse transcription PCR (RT-PCR) tests have been developed for rabies but only been used as a confirmatory test. Real-time PCR-based tests which have higher sensitivity and objective diagnostic thresholds and allow samples to be stored at room temperature have been promising since 2005, but require a real-time PCR machine and skilled workers with experience in molecular diagnostics. In an international evaluation a single TaqMan LN34 assay could detect Lyssavirus with high sensitivity (99.90%) across the genus and high specificity (99.68%) when compared to the DFA test. It will become the primary post-mortem rabies diagnostic test where possible.

Epidemiology

Classic rabies virus is prevalent throughout most of the world and can be carried by any warm blooded mammal. The other lyssaviruses have much less diversity in carriers. Only select hosts can carry each of these viral species. Also, these other species are particular only to a specific geographic area. Bats are known to be an animal vector for all identified lyssaviruses except the Mokola virus.

See also

* Bat-borne virus

References

Further reading

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External links

Rhabdoviridae

Lyssavirus



ICTV

{{Taxonbar, from=Q940434

Lyssaviruses
Virus genera
Chiroptera-borne diseases