West Caucasian bat lyssavirus

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.[5]

This image shows an example of the structure of a negative sense single stranded RNA virus with a glycoprotein.[6]

Rabies viruses were found in bats as far back as 1954 in Germany. However, until a bat worker in Finland died as a result of rabies in 1985, few cases had been noted. Increased surveillance and documentation in the 1986 and 1987 revealed several additional cases. These virus strains mostly consisted of European bat lyssavirus type 1 (EBLV-1) and European bat lyssavirus type 2 (EBLV-2). From 1977 to 2011, 961 cases of rabies were reported in Europe. 91% were EBLV-1. The rest of the cases were suspected to be EBLV-2 and all but 3 have been confirmed. The 3 unconfirmed cases resulted in the discovery of West Caucasian bat lyssavirus (WCBL) in southwest Russia in 2002 and the Bokeloh bat lyssavirus in Germany in 2010.[7]

West Caucasian bat lyssavirus (WCBL) is a bullet shaped negative sense single stranded RNA virus. WCBL is composed of an internal helical nucleocapsid and a lipid envelope derived from the host cell.[4] The virus contains knobbed spikes that protrude from the membrane to aid in host membrane fusion. In addition, WCBL, along with other lyssaviruses, has a glycoprotein which is important in mediating viral entry.[4]

This is an image of the genome of West Caucasian bat lyssavirus, which comprises five main genes: N, P, M, G, and L.

The WCBL contains a linear genome that is 12,278 base pairs in length and comprises five main genes, denoted N, P, M, G, and L. Gene N encodes for the nucleoprotein, P encodes for the phosphoprotein, M encodes for matrix proteins, G encodes for the glycoprotein, and L encodes for the polymerase.[8] WCBL must encode for an RNA-dependent RNA polymerase (RdRp) in its genome in order for viral replication and synthesis to occur because it is a negative single-strand RNA virus. In comparison to other lyssaviruses,  WCBL has a shorter trailer region of 57 nucleotides (as opposed to 69-70), but a longer non-coding region specifically in the glycoprotein gene at 697 nucleotides.[9] These differences have resulted in its classification into its own phylogroup. The West Caucasian bat lyssavirus also contains an open reading frame within the G gene which led researchers to believe parts of the glycoprotein were transcribed independently. However, a lack of a transcription initiation signal near the internal open reading frame has since confirmed that the glycoprotein is not transcribed in separate segments.[9]

The replication cycle for WCBL has not been specifically studied; however, it is said to be very similar to that of general lyssavirus, so the information listed below is regarding the genus as a whole.

The WCBL virus is closely related to rabies. Although, WCBL has not yet infected humans, there is great risk due to its similar structure to other lyssaviruses which are known to infect humans. Unfortunately, the current rabies vaccine is not effective against WCBL as a result of the WCBL’s slight divergence from other lyssaviruses. Therefore, if this virus begins to infect humans, the rabies vaccine will need to be improved to include effective antibodies for WCBL.[12]

WCBL initially infects muscle tissue in the bats. As the virus progresses, it moves into the nervous tissue in both the PNS and CNS.[12] Although no studies have been completed thus far on the mammalian tropism of the WCBL virus, tropism for another more recently discovered lyssavirus, Australian Bat Lyssavirus (ABLV) has been explored. A variety of mammalian cell types including rabbits, other small rodents, monkeys, horses, and humans have shown to be permissive to ABVL. This led researchers to believe that the receptor of entry is likely conserved across several mammalian species. More research is necessary to determine if a variety of mammalian cell types are also permissive to WCBL virus.[14]

There have been a few cases of outbreaks of WCBL. One was noted in Russia in 2002, which is the year that the virus was isolated.[7] A possible outbreak was noted in Kenya in 2008.[3]

In order to gain an understanding of the susceptibility and pathogenesis of the West Caucasian bat lyssavirus (WCBL), big brown bats (Eptesicus fuscus) were inoculated with the virus intramuscularly in the deltoid muscle, in the neck, or orally. Blood and saliva samples were taken during disease progression and tissue samples were analyzed post-mortem. Specific tissues of interest included the brain, salivary glands, brown fat, lung, kidney, and bladder. Three bats died during the lethargic stage of viral infection (days 10 to 18), all of which were inoculated in the neck. Of those that died, only the tissue samples from the brain contained the infectious virus. However, both lung and salivary gland tissue contained viral RNA. Two of the three bats had viral RNA present in the bladder and in brown fat tissue as well. None of these three bats had viral RNA present in the kidney. All bats that survived were euthanized at 6 months. No viral particles were detected in the brain and salivary gland tissue samples of these bats. Of all the bats surveyed, only one of the three that died from viral infection had viral RNA present in the saliva at the time of death.[15]

WCBL antibodies were found in the serum of 4 of 7 bats that received intramuscular inoculation from a few weeks post-inoculation to the end of observation at 6 months. Those that died as a result of infection did not have any WCBL antibodies, a likely result of a shorter incubation period experienced from neck inoculation. None of the bats inoculated orally developed a serological response or the disease. This study indicates that the progression of WCBL infection is dependent on the location of inoculation. Further research is needed to develop a more complete understanding of inoculation route, pathogen adaptation, and host response.

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