A Recombinant Chimeric La Crosse Virus Expressing the Surface Glycoproteins of Jamestown Canyon Virus Is Immunogenic and Protective against Challenge with either Parental Virus in Mice or Monkeys

Bennett, Richard S.; Gresko, Anthony K; Nelson, J. Arly; Murphy, Brian R.; Whitehead, Stephen S.

doi:10.1128/jvi.02327-10

Cited by 22 publications

(26 citation statements)

References 28 publications

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“…In additional studies using an attenuated CSG virus clone, neurovirulence was primarily determined by the L segment, but again the neurovirulence phenotype also appeared dependent on the other genomic segments [180,189]. More recently, a recombinant virus containing the LACV backbone with the M ORF from JCV (rLACV/JCV) showed that the chimeric virus was highly attenuated and unable to cause disease after either IP or IC inoculation at high doses, a surprising result considering both parental LACV and JCV viruses were highly neurovirulent [190]. Taken together, the results of these studies suggest that interactions between multiple CSG viral proteins encoded from multiple genomic segments determine CSG virus virulence.…”

Section: Neuropathogenesis – Molecular Mechanismsmentioning

confidence: 99%

“…Individual CSG virus proteins may have unexpected phenotypes when expressed outside of their specific genetic context. This may be an advantageous feature in terms of vaccine development, as the highly attenuated rLACV/JCV virus was highly immunogenic and when mice and monkeys were immunized with it, they were protected from subsequent LACV, TAHV, and JCV challenge [190]. However, if reassortants between the CSG viruses can have unique phenotypes from either parental virus, it is possible that more virulent novel reassortants may arise.…”

Section: Neuropathogenesis – Molecular Mechanismsmentioning

confidence: 99%

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Throw out the Map: Neuropathogenesis of the Globally Expanding California Serogroup of Orthobunyaviruses

Evans

Peterson

2019

Viruses

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The California serogroup (CSG) comprises 18 serologically and genetically related mosquito-borne orthobunyaviruses. Of these viruses, at least seven have been shown to cause neurological disease in humans, including the leading cause of pediatric arboviral encephalitis in the USA, La Crosse virus. Despite the disease burden from these viruses, much is still unknown about the CSG viruses. This review summarizes our current knowledge of the CSG viruses, including human disease and the mechanisms of neuropathogenesis.

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Section: Neuropathogenesis – Molecular Mechanismsmentioning

confidence: 99%

Section: Neuropathogenesis – Molecular Mechanismsmentioning

confidence: 99%

Throw out the Map: Neuropathogenesis of the Globally Expanding California Serogroup of Orthobunyaviruses

Evans

Peterson

2019

Viruses

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“…Currently, there is no vaccine available to inhibit LACV infection [4, 5] or therapy to treat virus-induced encephalitis [2]. Thus, a better understanding of the mediators of viral pathogenesis in the central nervous system (CNS) as well as the mechanisms by which adults are protected from the development of encephalitis is necessary to mitigate disease impact.…”

Section: Introductionmentioning

confidence: 99%

Lymphocytes have a role in protection, but not in pathogenesis, during La Crosse Virus infection in mice

Winkler

Myers

Woods

et al. 2017

J Neuroinflammation

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BackgroundLa Crosse Virus (LACV) is a primary cause of pediatric viral encephalitis in the USA and can result in severe clinical outcomes. Almost all cases of LACV encephalitis occur in children 16 years or younger, indicating an age-related susceptibility. This susceptibility is recapitulated in a mouse model where weanling (3 weeks old or younger) mice are susceptible to LACV-induced disease, and adults (greater than 6 weeks) are resistant. Disease in mice and humans is associated with infiltrating leukocytes to the CNS. However, what cell types are infiltrating into the brain during virus infection and how these cells influence pathogenesis remain unknown.MethodsIn the current study, we analyzed lymphocytes recruited to the CNS during LACV-infection in clinical mice, using flow cytometry. We analyzed the contribution of these lymphocytes to LACV pathogenesis in weanling mice using knockout mice or antibody depletion. Additionally, we studied at the potential role of these lymphocytes in preventing LACV neurological disease in resistant adult mice.ResultsIn susceptible weanling mice, disease was associated with infiltrating lymphocytes in the CNS, including NK cells, CD4 T cells, and CD8 T cells. Surprisingly, depletion of these cells did not impact neurological disease, suggesting these cells do not contribute to virus-mediated damage. In contrast, in disease-resistant adult animals, depletion of both CD4 T cells and CD8 T cells or depletion of B cells increased neurological disease, with higher levels of virus in the brain.ConclusionsOur current results indicate that lymphocytes do not influence neurological disease in young mice, but they have a critical role protecting adult animals from LACV pathogenesis. Although LACV is an acute virus infection, these studies indicate that the innate immune response in adults is not sufficient for protection and that components of the adaptive immune response are necessary to prevent virus from invading the CNS.

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“…Ochlerotatus communis is a vector of Jamestown Canyon virus (JCV) and snow shoe hare virus (SSHV) in North America (McLean et al 1981; Heard et al 1990), but the clinical significance of O. churchillensis has not yet been studied. Both viruses are widely distributed across temperate areas of North America, and several boreal Aedes Meigen, 1818 and Ochlerotatus Lynch Arribálzaga, 1891 species are the primary vectors (Grimstad 1988; Andreadis et al 2008; Bennett et al 2012). Although JCV antibodies have been detected in moose, elk, bison, mule deer, domestic bovine and equine, white-tailed deer is the only known amplifying host in the natural transmission cycle of the virus (Grimstad 1988; Rust et al 1999).…”

Section: Introductionmentioning

confidence: 99%

“…SSHV was isolated for the first time from snowshoe hare ( Lepus americanus Erxleben, 1777; Mammalia: Leporidae) in Montana, United States of America in 1959 (Burgdorfer et al 1961). However, its antibodies also have recently been detected in several small vertebrates and domestic animals such as equine, cattle, dog, and chicken (Bennett et al 2012). The symptoms of SSHV infection in humans include fever, headache, vomiting, meningitis, and encephalitis (Fauvel et al 1980).…”

Section: Introductionmentioning

confidence: 99%

Phylogenetics and molecular identification of theOchlerotatus communiscomplex (Diptera: Culicidae) using DNA barcoding and polymerase chain reaction-restriction fragment length polymorphism

2013

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TheOchlerotatus communis(De Geer, 1776) complex consists of four cryptic mosquito species in North America, including:O. communis,Ochlerotatus churchillensis(Ellis and Brust, 1973),Ochlerotatus nevadensis(Chapman and Barr, 1964), andOchlerotatus tahoensis(Dyar, 1916). Most of the morphological characters used for the identification of these species are quantitative and overlap across species. Here we evaluated the efficacy of DNA barcoding for identification of three members of thecommuniscomplex (O. nevadensisis not included in this study) and developed diagnostic restriction fragment length polymorphism (RFLP) patterns forO. communisandO. churchillensis. A phylogeny of 23OchlerotatusLynch Arribálzaga, 1891 species was inferred using mitochondrial cytochromecoxidase subunit I gene sequences. All species included in our analysis within theO. communiscomplex were delineated using cytochromecoxidase subunit I barcodes. However, this complex was recovered as paraphyletic with respect toOchlerotatus abserratus(Felt and Young, 1904) andOchlerotatus implicatus(Vockeroth, 1954), indicating the need for increased genetic and taxonomic sampling to infer the phylogenetic relationships of these taxa. The RFLP profile for multiple field specimens ofO. communiswas distinct from all RFLP patterns forO. churchillensis, and this method can be used as an efficient molecular method for the identification these species.

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A Recombinant Chimeric La Crosse Virus Expressing the Surface Glycoproteins of Jamestown Canyon Virus Is Immunogenic and Protective against Challenge with either Parental Virus in Mice or Monkeys

Abstract: La Crosse virus (LACV) and Jamestown Canyon virus (JCV), family

Cited by 22 publications

References 28 publications

Throw out the Map: Neuropathogenesis of the Globally Expanding California Serogroup of Orthobunyaviruses

Throw out the Map: Neuropathogenesis of the Globally Expanding California Serogroup of Orthobunyaviruses

Lymphocytes have a role in protection, but not in pathogenesis, during La Crosse Virus infection in mice

Phylogenetics and molecular identification of theOchlerotatus communiscomplex (Diptera: Culicidae) using DNA barcoding and polymerase chain reaction-restriction fragment length polymorphism

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