Serogroup classification of viruses has traditionally been a way to group similar viruses based on the cross-reactivity of the antibodies they elicit. Additionally, there is overlap between the mosquito vectors and vertebrate hosts utilized by these viruses 1. TAHV is widespread throughout Europe, Asia, and Africa, and INKV is primarily found in Scandinavia, but overlaps with TAHV in Russia 1. LACV, SSHV, and JCV are all found in the USA, with SSHV and JCV extending into Canada 1. These five viruses are found throughout most of the world with discrete, but sometimes overlapping, geographic distributions. Several viruses within the CSG have been reported to cause neuroinvasive disease in humans, including La Crosse virus (LACV), Snowshoe hare virus (SSHV), Tahyna virus (TAHV), Jamestown Canyon virus (JCV), and Inkoo virus (INKV) 1, 2, 3, 4, 5. The California Serogroup (CSG) is a group of at least 18 antigenically and genetically related mosquito-borne viruses in the Family Peribunyaviridae of the Genus Orthobunyavirus 1. Thus, NAb titers, which are the gold-standard for diagnosing the etiologic agent for viral encephalitis, may not clearly differentiate between different CSG viruses. Interestingly, a fourfold difference in NAb titer between the inoculum virus and the other CSG viruses was not always observed. LACV, SSHV, and INKV elicited the highest amount of cross-reactive NAb. Overall, the results from these studies show that the CSG viruses induced high levels of NAb against the inoculum virus, and differing amounts of cross-reactive NAb against heterologous viruses. Mice were inoculated with individual viruses and the NAb activity of plasma samples was compared by plaque reduction neutralization tests against all five viruses. To help elucidate NAb relationships between neuroinvasive CSG viruses, we directly compared the cross-reactivity of NAb between LACV, SSHV, TAHV, JCV, and INKV. Diagnosis of specific CSG viruses is complicated by the high degree of antibody cross-reactivity between them, with laboratory standards requiring a fourfold higher titer of neutralizating antibody (NAb) activity to positively identify the etiologic virus. The California Serogroup (CSG) of Orthobunyaviruses comprises several viruses capable of causing neuroinvasive disease in humans, including La Crosse (LACV), Snowshoe Hare (SSHV), Tahyna (TAHV), Jamestown Canyon (JCV), and Inkoo (INKV) viruses.
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