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The reovirus sigma1s protein is a determinant of hematogenous but not neural virus dissemination in mice.

ABSTRACT: Nonstructural protein ?1s is a critical determinant of hematogenous dissemination by type 1 reoviruses, which reach the central nervous system (CNS) by a strictly blood-borne route. However, it is not known whether ?1s contributes to neuropathogenesis of type 3 reoviruses, which disseminate by both vascular and neural pathways. Using isogenic type 3 viruses that vary only in ?1s expression, we observed that mice survived at a higher frequency following hind-limb inoculation with ?1s-null virus than when inoculated with wild-type virus. This finding suggests that ?1s is essential for reovirus virulence when inoculated at a site that requires systemic spread to cause disease. Wild-type and ?1s-null viruses produced comparable titers in the spinal cord, suggesting that ?1s is dispensable for invasion of the CNS. Although the two viruses ultimately achieved similar peak titers in the brain, loads of wild-type virus were substantially greater than those of the ?1s-null mutant at early times after inoculation. In contrast, wild-type virus produced substantially higher titers than the ?1s-null virus in peripheral organs to which reovirus spreads via the blood, including the heart, intestine, liver, and spleen. Concordantly, viral titers in the blood were higher following infection with wild-type virus than following infection with the ?1s-null mutant. These results suggest that differences in viral brain titers at early time points postinfection are due to limited virus delivery to the brain by hematogenous pathways. Transection of the sciatic nerve prior to hind-limb inoculation diminished viral spread to the spinal cord. However, wild-type virus retained the capacity to disseminate to the brain following sciatic nerve transection, indicating that wild-type reovirus can spread to the brain by the blood. Together, these results indicate that ?1s is not required for reovirus spread by neural mechanisms. Instead, ?1s mediates hematogenous dissemination within the infected host, which is required for full reovirus neurovirulence.

SUBMITTER: Boehme KW

PROVIDER: S-EPMC3209282 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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The reovirus sigma1s protein is a determinant of hematogenous but not neural virus dissemination in mice.

Boehme Karl W KW Frierson Johnna M JM Konopka Jennifer L JL Kobayashi Takeshi T Dermody Terence S TS

Journal of virology 20110914 22

Nonstructural protein σ1s is a critical determinant of hematogenous dissemination by type 1 reoviruses, which reach the central nervous system (CNS) by a strictly blood-borne route. However, it is not known whether σ1s contributes to neuropathogenesis of type 3 reoviruses, which disseminate by both vascular and neural pathways. Using isogenic type 3 viruses that vary only in σ1s expression, we observed that mice survived at a higher frequency following hind-limb inoculation with σ1s-null virus t ...[more]

PMID: 21917967

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The reovirus sigma1s protein is a determinant of hematogenous but not neural virus dissemination in mice.

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The reovirus sigma1s protein is a determinant of hematogenous but not neural virus dissemination in mice.

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