La Crosse virus infectivity, pathogenesis, and immunogenicity in mice and monkeys

Abstract

Background: La Crosse virus (LACV), family Bunyaviridae, was first identified as a human pathogen in 1960 after its isolation from a 4 year-old girl with fatal encephalitis in La Crosse, Wisconsin. LACV is a major cause of pediatric encephalitis in North America and infects up to 300,000 persons each year of which 70-130 result in severe disease of the central nervous system (CNS). As an initial step in the establishment of useful animal models to support vaccine development, we examined LACV infectivity, pathogenesis, and immunogenicity in both weanling mice and rhesus monkeys.

Novel Reporter Mouse Reveals Constitutive and Inflammatory Expression of IFN-β In Vivo

“…We used these mice (briefly named ⌬␤-luc) to characterize in vivo expression of IFN-␤ upon infection with either influenza A or La Crosse virus. We found that the kinetics and tissue distribution of IFN-␤ gene expression correlated with the known temporal distribution of viral replication (16). We further reveal that several tissues exhibit low levels of constitutive IFN-␤ expression.…”

“…LACV is a bunyavirus that is highly virulent for mice of young age (16). It causes severe neurological disease within 5-8 days after peripheral infection.…”

Encephalitic Arboviruses: Emergence, Clinical Presentation, and Neuropathogenesis

“…In vitro and in vivo studies have shown that neurons undergo morphologic changes that are characteristic of apoptosis, that is, nuclear and membrane condensation, after infection with several encephalitic flaviviruses, including WNV [183], JEV [154], TBEV [184], and alphaviruses [145,185,186]. Neuronal degeneration, necrosis, and apoptosis were also demonstrated in various CNS regions in mice infected with LACV [146].…”

“…Within the CNS, neurons are the main target cells for encephalitic flaviviruses [154,170], alphaviruses [107,145], and members of the Bunyaviridae and Reoviridae [146,171,172]. Arboviral infection of other cell types of the CNS has also been reported (Table 2), and recent in vitro studies with ZIKV suggest it may target neural progenitor cells [173][174][175][176].…”

“…CNS invasion via olfactory bulb has been demonstrated for several encephalitic arboviruses, including SLEV [142], MVEV [143], VEEV [144], EEEV [145], and LACV [146]. Soon after onset of viremia, viral particles exit the fenestrated capillaries beneath the mucosa of the nasal cavity.…”