Abstract
The California serogroup of orthobunyaviruses comprises a group of mosquitoborne viruses, including La Crosse (LACV), snowshoe hare (SSHV), Tahyna (TAHV), Jamestown Canyon (JCV), and Inkoo (INKV) viruses, that cause neurologic disease in humans of differing ages with varying incidences. To determine how the pathogenesis of these viruses differs, we compared their ability to induce disease in mice and replicate and induce cell death in vitro. In mice, LACV, TAHV, and SSHV induced neurologic disease after intraperitoneal and intranasal inoculation, and JCV induced disease only after intranasal inoculation. INKV rarely induced disease, which correlated with less viral antigen in the brain than the other viruses. In vitro, all viruses replicated to high titers; however, LACV, SSHV, and TAHV induced high cell death, whereas JCV and INKV did not. Results demonstrated that CSG viruses differ in neuropathogenesis in vitro and in vivo, which correlates with the differences in pathogenesis reported in humans.
Highlights
The California serogroup of orthobunyaviruses comprises a group of mosquitoborne viruses, including La Crosse (LACV), snowshoe hare (SSHV), Tahyna (TAHV), Jamestown Canyon (JCV), and Inkoo (INKV) viruses, that cause neurologic disease in humans of differing ages with varying incidences
All viruses co-localized with the neuronal marker microtubule-associated protein 2, indicating that all California serogroup (CSG) viruses primarily infected neurons within the central nervous system (CNS) (Figure 4, panel C). These results demonstrate that La Crosse virus (LACV), snowshoe hare virus (SSHV), Tahyna virus (TAHV), and Jamestown Canyon virus (JCV) are neurovirulent in mice when inoculated intranasally, whereas Inkoo virus (INKV) appears to be less neurovirulent and infects fewer neurons within the CNS
LACV, TAHV, and SSHV were capable of causing neuroinvasive disease, a finding only observed in weanling mice
Summary
The California serogroup of orthobunyaviruses comprises a group of mosquitoborne viruses, including La Crosse (LACV), snowshoe hare (SSHV), Tahyna (TAHV), Jamestown Canyon (JCV), and Inkoo (INKV) viruses, that cause neurologic disease in humans of differing ages with varying incidences. Certain strains of TAHV, but not JCV, have been shown to cause neurologic disease in weanling Swiss Webster mice after intraperitoneal inoculation, both viruses were capable of replicating in the brain after intracranial inoculation [40,41]. In these studies, only weanling mice were used, and age-dependent susceptibility was not evaluated
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