Abstract
Lagos bat virus (LBV) is a phylogroup II lyssavirus exclusively found in Africa. Previous studies indicated that this virus is lethal to mice after intracranial and intramuscular inoculation. The antigenic composition of LBV differs substantially from that of rabies virus (RABV) and current rabies vaccines do not provide cross protection against phylogroup II lyssaviruses. To investigate the potential role of the LBV matrix protein (M) and glycoprotein (G) in pathogenesis, reverse genetics technology was used to construct recombinant viruses. The genes encoding the glycoprotein, or the matrix and glycoprotein of the attenuated RABV strain SPBN, were replaced with those of LBV resulting in SPBN-LBVG and SPBN-LBVM-LBVG, respectively. To evaluate the immunogenicity of the LBV G, the recombinant RABV SPBNGAS-LBVG-GAS was constructed with the LBV G inserted between two mutated RABV G genes (termed GAS). All the recombinant viruses were lethal to mice after intracranial (i.c.) inoculation although the pathogenicity of SPBNGAS-LBVG-GAS was lower compared to the other recombinant viruses. Following intramuscular (i.m.) inoculation, only SPBN-LBVM-LBVG was lethal to mice, indicating that both the M and G of LBV play a role in the pathogenesis. Most interestingly, serum collected from mice that were inoculated i.m. with SPBNGAS-LBVG-GAS neutralized phylogroup I and II lyssaviruses including RABV, Duvenhage virus (DUVV), LBV, and Mokola virus (MOKV), indicating that this recombinant virus has potential to be developed as a pan-lyssavirus vaccine.
Highlights
The Lyssavirus genus consists of 14 viral species and three putative species, grouped into three phylogroups [1,2,3]
We demonstrate that the rabies virus (RABV) backbone can express functional Lagos bat virus (LBV) genes, and that both the M and G genes of LBV play a role in pathogenicity
The successful rescue of RABV recombinant viruses expressing LBV proteins, indicates that RABV genes can interact with the LBV M and G genes, similar to previous studies [18,28,29,58]
Summary
The Lyssavirus genus consists of 14 viral species and three putative species, grouped into three phylogroups [1,2,3]. While all members of the lyssavirus genus are capable of causing a fatal encephalitic disease, rabies virus (RABV) in phylogroup I is responsible for most human and animal rabies cases and is globally distributed. Case reports of LBV are limited, pathogenicity studies in mice have indicated that the virus is pathogenic to mice when inoculated via the intramuscular (i.m.) and intracranial (i.c.) route with distinct pathogenicity profiles observed between different LBV lineages [6,10,11]. Gene exchange between RABV strains with different pathogenicity profiles has been performed in previous studies mostly focusing on the G protein [13,16,17,18,19,20]. A number of studies have demonstrated that replacement of the G gene from a non-pathogenic RABV strain with that of a pathogenic strain results in a pathogenic RABV strain [13,16,17,20]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
