La Crosse Virus Shows Strain-Specific Differences in Pathogenesis.

Sarah N Wilson,Philip M Armstrong,Krisangel López,Theodore G Andreadis,Gillian Eastwood,Sheryl Coutermash-Ott,Danielle L Porier,Dawn I Auguste,Albert J Auguste

doi:10.3390/pathogens10040400

Abstract

La Crosse virus (LACV) is the leading cause of pediatric viral encephalitis in North America, and is an important public health pathogen. Historically, studies involving LACV pathogenesis have focused on lineage I strains, but no former work has explored the pathogenesis between or within lineages. Given the absence of LACV disease in endemic regions where a robust entomological risk exists, we hypothesize that some LACV strains are attenuated and demonstrate reduced neuroinvasiveness. Herein, we compared four viral strains representing all three lineages to determine differences in neurovirulence or neuroinvasiveness using three murine models. A representative strain from lineage I was shown to be the most lethal, causing >50% mortality in each of the three mouse studies. However, other strains only presented excessive mortality (>50%) within the suckling mouse neurovirulence model. Neurovirulence was comparable among strains, but viruses differed in their neuroinvasive capacities. Our studies also showed that viruses within lineage III vary in pathogenesis with contemporaneous strains, showing reduced neuroinvasiveness compared to an ancestral strain from the same U.S. state (i.e., Connecticut). These findings demonstrate that LACV strains differ markedly in pathogenesis, and that strain selection is important for assessing vaccine and therapeutic efficacies.

Highlights

The family Peribunyaviridae is among the largest known viral families, with >170 known members reported to date
To compare pathogenesis among La Crosse virus (LACV) strains, we evaluated the differences in neuroinvasive potential and neurovirulence among four viral strains from all three genetic lineages in multiple murine models
Our studies show that viruses within lineage III vary in pathogenesis with a recent strain having reduced neuroinvasiveness compared to an ancestral strain from the same state

Summary

Introduction

The family Peribunyaviridae is among the largest known viral families, with >170 known members reported to date. Within this family, the genus Orthobunyavirus is a important, and nearly globally distributed, group with an exceptionally diverse vertebrate host and arthropod vector host range [1]. La Crosse virus (LACV) is among the most important members of the California serogroup of orthobunyaviruses and the leading cause of pediatric viral encephalitis in North America [2]. Previous studies have shown that the NSS of the S segment suppresses the vertebrate type I interferon response, thereby increasing LACV pathogenesis [9]. Other studies have shown that LACV is under polygenic control, but that the M segment plays an important role in its virulence [10,11,12]

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Conclusion