Passage of the mouse-adapted rabies virus strain CVS-24 (where CVS is challenge virus standard) in BHK cells results in the rapid selection of a dominant variant designated CVS-B2c that differs genotypically and phenotypically from the dominant variant CVS-N2c present in mouse-brain-or neuroblastoma-cell-passaged CVS-24. The glycoprotein of CVSB2c has 10 amino acid substitutions compared with that of CVS-N2c. Because CVS-B2c can be reproducibly selected in BHK cells, it is likely to be a conserved minor subpopulation of CVS-24. CVS-N2c is more neurotropic in vitro and in vivo than CVS-B2c, which replicates more readily in nonneuronal cells in vitro and in vivo. These characteristics appear to be relevant to the pathogenicity of the two variants. CVS-N2c is more pathogenic for adult mice than CVS-B2c. In contrast, CVS-B2c is more pathogenic for neonatal mice. These differences in pathogenicity are reflected in the selection pattern when mixtures of CVS-N2c and CVS-B2c were used to infect neonatal and adult mice. Although CVS-N2c was highly selected in adult mice, no selection for either variant was seen in neonates, suggesting that certain aspects of development, such as maturation of the nervous and immune systems, may contribute to the selection process. We speculate that the existence of different variants within a rabies virus strain may facilitate the virus in overcoming barriers to its spread, both within the host and between species.By far the predominant target of rabies virus infection in vivo is the neuron (1). Nevertheless, it has been shown that rabies virus can infect myocytes before the virus infection reaches neurons in the spinal cord or dorsal root ganglia (1, 2). In addition, high titers of rabies virus can be produced in mucogenic acinary cells of the salivary glands during the final phase of infection. In vitro experimentation has shown that street rabies virus can infect macrophages (3) and fixed rabies virus strains can infect murine lymphocytes and human lymphoblast T cells (4). However, it is not clear whether virus replication in nonneuronal tissue, with the exception of the salivary glands, actually represents an integral part of the pathogenesis of rabies nor it is known whether a single virus population or different subpopulations of a particular strain are responsible for the infection of neuronal and nonneuronal cells. In this context, it has been shown, in mice persistently infected with lymphocytic choriomeningitis virus (LCMV), that different variants of the same LCMV strain are associated with infection of neuronal cells, liver cells, or spleen cells (5, 6). Because of the high mutation rates resulting from the lack of proofreading by RNA polymerases RNA virus strains exist as quasispecies (7). It has been demonstrated that in a constant environment quasispecies contain a stable dominant virus species within a pool of viruses with related but often extremely heterogeneous genomes (7-9). Such complexity endows RNA viruses with an enormous capacity to adapt to changing host...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.