Type 3 reovirus neuroinvasion after intramuscular inoculation: Viral genetic determinants of lethality and spinal cord infection

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Abstract

To better understand the mechanisms by which neurotropic viruses invade peripheral nerve pathways and produce CNS disease, we defined the type 3 (T3) reovirus genes that are determinants of the capacity of reovirus T3 strain Dearing (T3D) and T3 clone 9 (C9) to infect the spinal cord and kill mice after hindlimb injection. T3D and C9 viruses are both highly virulent (LD50 < 101 PFU) after intracranial injection of neonatal mice. However, C9 is significantly more lethal than T3D after either intramuscular injection (LD50 < 101 vs LD50 104 PFU) or peroral injection (LD50 103.4 vs LD50 > 108.3 PFU). Using reassortant viruses containing different combinations of genes derived from T3D and C9, we found that the S1 gene, encoding the cell attachment protein sigma 1 and the nonstructural protein sigma 1s, and the L3 gene, encoding the core shell protein lambda 1 were the primary determinants of lethality after intramuscular injection. The L3 gene and the L2 gene encoding spike protein, lambda 2, determined differences in spinal cord titer after intramuscular injection. A C9 × T3D mono-reassortant containing all T3D genes except for the C9-derived L3 was lethal after peroral injection. These studies indicate that the S1, L2, and L3 genes all play a potential role in neuroinvasiveness and provide the first identification of a role in pathogenesis for the L3 gene. © 2002 Elsevier Science (USA).

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Mann, M. A., Tyler, K. L., Knipe, D. M., & Fields, B. N. (2002). Type 3 reovirus neuroinvasion after intramuscular inoculation: Viral genetic determinants of lethality and spinal cord infection. Virology, 303(2), 213–221. https://doi.org/10.1006/viro.2002.1698

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