Host Switching in Lyssavirus History from the Chiroptera to the Carnivora Orders

Abstract

Lyssaviruses are unsegmented RNA viruses causing rabies. Their vectors belong to the Carnivora and Chiroptera orders. We studied 36 carnivoran and 17 chiropteran lyssaviruses representing the main genotypes and variants. We compared their genes encoding the surface glycoprotein, which is responsible for receptor recognition and membrane fusion. The glycoprotein is the main protecting antigen and bears virulence determinants. Point mutation is the main force in lyssavirus evolution, as Sawyer's test and phylogenetic analysis showed no evidence of recombination. Tests of neutrality indicated a neutral model of evolution, also supported by globally high ratios of synonymous substitutions (d S ) to nonsynonymous substitutions (d N ) (>7). Relative-rate tests suggested similar rates of evolution for all lyssavirus lineages. Therefore, the absence of recombination and similar evolutionary rates make phylogeny-based conclusions reliable. Phylogenetic reconstruction strongly supported the hypothesis that host switching occurred in the history of lyssaviruses. Indeed, lyssaviruses evolved in chiropters long before the emergence of carnivoran rabies, very likely following spillovers from bats. Using dated isolates, the average rate of evolution was estimated to be roughly 4.3 ؋ 10 ؊4 d S /site/year. Consequently, the emergence of carnivoran rabies from chiropteran lyssaviruses was determined to have occurred 888 to 1,459 years ago. Glycoprotein segments accumulating more d N than d S were distinctly detected in carnivoran and chiropteran lyssaviruses. They may have contributed to the adaptation of the virus to the two distinct mammal orders. In carnivoran lyssaviruses they overlapped the main antigenic sites, II and III, whereas in chiropteran lyssaviruses they were located in regions of unknown functions.

Evolutionary timescale of rabies virus adaptation to North American bats inferred from the substitution rate of the nucleoprotein gene

“…The relative consistency of m estimations between datasets supports the hypothesis of a molecular clock governing evolution of the RV N gene Badrane & Tordo, 2001). This was no doubt due to the lack of positively selected codons along the N gene found here and elsewhere Kuzmin et al, 2004).…”

“…The establishment of non-chiropteran rabies (globally) and the development of RV variants in the Americas have been dated to have occurred between 542 and 1113 (Badrane & Tordo, 2001). Another study estimated the TMRCA of current global RV diversity to be within the last 500 years, implying that RV variants associated with New World bats originated from RV introduced during European colonization , a hypothesis not refuted by our estimation of the TMRCA of current bat RV diversity in the Americas.…”

Prevalence of Neutralizing Antibodies to Rabies Virus in Serum of Seven Species of Insectivorous Bats From Colorado and New Mexico, United States

“…It is also clear that numerous species of bats throughout the world serve as reservoirs of rabies viruses and other lyssaviruses. Rabies virus may have evolved initially in bats before becoming established in carnivore reservoirs through spillover and host switching, although this concept has not yet been resolved (Badrane and Tordo, 2001;Hughes et al, 2005;Davis et al, 2006). Our study adds to several reports indicating that a substantial fraction of apparently healthy bats have neutralizing antibodies to rabies virus (Constantine et al, 1968;Trimarchi and Debbie, 1977;Steece and Altenbach, 1989;Salas-Rojas et al, 2004;Shankar et al, 2004;Streicker et al, 2012), suggesting that they have undergone significant exposure to the virus, but that the infection failed to progress to clinical disease.…”

Addition of a single N-glycan to street rabies virus glycoprotein enhances virus production

“…The sequon at Asn 319 is conserved in the G protein of RABVs and other lyssaviruses (Badrane & Tordo, 2001), indicating that it probably has an important role in the G protein function. Our results showed that an N-glycan at Asn 319 is important for the function of the street RABV G protein.…”