Dynamics of rabies virus quasispecies during serial passages in heterologous hosts

Abstract

To understand the mutations and genetic rearrangements that allow rabies virus infections of new hosts and adaptation in nature, the quasispecies structure of the nucleoprotein and glycoprotein genes as well as two noncoding sequences of a rabies virus genome were determined. Gene sequences were obtained from the brain and from the salivary glands of the original host, a naturally infected European fox, and after serial passages in mice, dogs, cats and cell culture. A relative genetic stasis of the consensus sequences confirmed previous results about the stability of rabies virus. At the quasispecies level, the mutation frequency varies, in the following order : glycoprotein region (21n9i10 N4 mutations per bp), noncoding sequence nucleoproteinphosphoprotein region (7n2-7n9i10 N4 mutations per bp) and nucleoprotein gene region (2n9-3n7i10 N4 mutations per bp). These frequencies varied according to the number, type of heterologous passages and the genomic region considered. The shape of the quasispecies structure was dramatically modified by passages in mice, in which the mutation frequencies increased by 12-31i10 N4 mutations per bp, depending on the region considered. Nonsynonymous mutations were preponderant particularly in the glycoprotein gene, stressing the importance of positive selection in the maintenance and fixation of substitutions. Two mechanisms of genomic evolution of the rabies virus quasispecies, while adapting to environmental changes, have been identified : a limited accumulation of mutations with no replacement of the original master sequence and a less frequent but rapid selective overgrowth of favoured variants.

Molecular study of the quasispecies evolution of a typical pigeon paramyxovirus type 1 after serial passages in pigeons by contact

“…Therefore, truncated HN proteins might be expressed at the surface of the cells and incorporated into newly formed virus particles, possibly with consequences for the binding abilities and the infectivity of the virus (Huang et al , 2004). However, the question arises whether these aberrant and defective genomic RNAs, detected inside the infected cells, are actually packaged into the newly formed virus particles, excreted and transmitted to susceptible hosts, as shown in other models (Cabot et al , 2000;Kissi et al , 1999;Wang et al , 2003). This question could be assessed by studying the virus heterogeneity after virus purification from both organs and cloacal and tracheal swabs.…”

“…The missing subpopulations might then represent a memory for the quasispecies (Ruiz-Jarabo et al. , 2000) and be undetectable by the technique used, or simply have disappeared during the contact passages (Kissi et al , 1999). Each contact would need to be studied to better understand this phenomenon.…”

Occurrence of Genetic Drift and Founder Effect during Quasispecies Evolution of the VP2 and NS3/NS3A Genes of Bluetongue Virus upon Passage between Sheep, Cattle, and Culicoides sonorensis

“…In addition to mutations introduced by their error-prone polymerases, RNA viruses also generate genomic variation by homologous and nonhomologous recombination and reassortment in those viruses with a segmented genome. Thus, RNA viruses exist as a heterogeneous population of closely related variants characterized by one or several dominant master nucleotide genome sequence(s) (quasispecies) (14,15,17,35). The quasispecies nature of RNA viruses confers significant adaptive potential through selection of mutants with the highest fitness in a new environment, which allows for rapid evolution (40).…”

Zoonotic and Animal Vector Mediated Encephalitides

“…Raccoons (Smith et al, 1995), as well as bats (silver-haired and eastern pipistrelle) are the most common animals to be infected in the U.S., with bats presenting more cryptic cases of rabies infections due to a lack of obvious bite wounds (Messenger et al, 2002). Mutations of the virus through serial passes through hosts can create quasispecies, suggesting a mechanism to the accommodation to a novel hosts (Morimoto et al, 1998;Kissi et al, 1999). Bourhy et al (1999) showed, through an analysis of European strains of the virus, local genetic differentiation is taking place, facilitated by physical barriers.…”