Comparative sequence analyses of La Crosse virus strain isolated from patient with fatal encephalitis, Tennessee, USA.
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ABSTRACT:
SUBMITTER: Lambert AJ
PROVIDER: S-EPMC4412244 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:We report the arthropod-borne pediatric encephalitic agent La Crosse virus in Aedes albopictus mosquitoes collected in Dallas County, Texas, USA, in August 2009. The presence of this virus in an invasive vector species within a region that lies outside the virus's historically recognized geographic range is of public health concern.
| S-EPMC2954019 | biostudies-literature
Project description:A bite from a La Crosse virus (LACV) infected Aedes mosquito can cause La Crosse encephalitis (LACE), which is a neuro-invasive disease that disproportionately affects children under the age of 16 in Southern Appalachia. The three vectors for LACV are Aedes albopictus (Skuse), Ae. japonicus (Theobald), and Ae. triseriatus (Say). Localized maps of the geographic distribution of vectors are practical tools for mosquito management personnel to target areas with high mosquito abundance. This study hypothesized that LACV vectors have unique species-specific spatial and temporal clusters. To test this, 44 sites were identified in Knox County, Tennessee for their land use/type. At each site, host-seeking mosquitoes were collected approximately every other week from May-October 2018. Spatial clusters of host-seeking mosquito collections for each of the three mosquito species were investigated using Kulldorff's spatial scan statistic, specifying a retrospective space-time Bernoulli model. Most vector clusters were identified in south-central Knox County while the seasonality of clusters varied by mosquito species. Clusters of Ae. albopictus were observed throughout the entire study period while clusters of Ae. japonicus and Ae. triseriatus only occurred May-June. The findings indicate that the relative abundance of LACV vectors were more abundant in south-central Knox County compared to the rest of the county. Of interest, these clusters spatially overlapped with previous LACE diagnosed cases. These findings are useful in guiding decisions on targeted mosquito control in Knox County and may be applied to other counties within Southern Appalachia.
| S-EPMC7470364 | biostudies-literature
Project description:BackgroundLa Crosse virus (LACV) (genus Orthobunyavirus, family Peribunyaviridae) is a mosquito-borne virus that causes pediatric encephalitis and accounts for 50-150 human cases annually in the USA. Human cases occur primarily in the Midwest and Appalachian regions whereas documented human cases occur very rarely in the northeastern USA.MethodsFollowing detection of a LACV isolate from a field-collected mosquito in Connecticut during 2005, we evaluated the prevalence of LACV infection in local mosquito populations and genetically characterized virus isolates to determine whether the virus is maintained focally in this region.ResultsDuring 2018, we detected LACV in multiple species of mosquitoes, including those not previously associated with the virus. We also evaluated the phylogenetic relationship of LACV strains isolated from 2005-2018 in Connecticut and found that they formed a genetically homogeneous clade that was most similar to strains from New York State.ConclusionOur analysis argues for local isolation and long-term persistence of a genetically distinct lineage of LACV within this region. We highlight the need to determine more about the phenotypic behavior of these isolates, and whether this virus lineage poses a threat to public health.
| S-EPMC7659055 | biostudies-literature
Project description:La Crosse virus (LACV) is a major cause of pediatric encephalitis and aseptic meningitis in the Midwestern, Mid-Atlantic, and Southern United States, where it is an emerging pathogen. The LACV Gc glycoprotein plays a critical role in the neuropathogenesis of LACV encephalitis as the putative virus attachment protein. Previously, we identified and experimentally confirmed the location of the LACV fusion peptide within Gc and generated a panel of recombinant LACVs (rLACVs) containing mutations in the fusion peptide as well as the wild-type sequence. These rLACVs retained their ability to cause neuronal death in a primary embryonic rat neuronal culture system, despite decreased replication and fusion phenotypes. To test the role of the fusion peptide in vivo, we tested rLACVs in an age-dependent murine model of LACV encephalitis. When inoculated directly into the CNS of young adult mice (P28), the rLACV fusion peptide mutants were as neurovirulent as the rLACV engineered with a wild-type sequence, confirming the results obtained in tissue culture. In contrast, the fusion peptide mutant rLACVs were less neuroinvasive when suckling (P3) or weanling (P21) mice were inoculated peripherally, demonstrating that the LACV fusion peptide is a determinant of neuroinvasion, but not of neurovirulence. In a challenge experiment, we found that peripheral challenge of weanling (P21) mice with fusion peptide mutant rLACVs protected from a subsequent WT-LACV challenge, suggesting that mutations in the fusion peptide are an attractive target for generating live-attenuated virus vaccines. Importantly, the high degree of conservation of the fusion peptide amongst the Bunyavirales and, structurally, other arboviruses suggests that these findings are broadly applicable to viruses that use a class II fusion mechanism and cause neurologic disease.
| S-EPMC9317099 | biostudies-literature
Project description:Unlike some members of the family Bunyaviridae which contain ambisense genomes, all La Crosse virus reading frames are translated from antigenome sense mRNAs. Nevertheless, La Crosse virus genome sense mRNAs or anti-mRNAs are initiated from antigenome templates. These are characterized by the same range of capped, nontemplated sequences at their 5' ends as mRNAs, but their 3' ends are presumed to be heterogenous, as they were not seen on RNA blots. The anti-mRNAs are estimated to be 15 to 30 times less abundant than mRNAs, but remarkably, this ratio is similar to that of functional genome sense mRNAs made from other bona fide ambisense segments. A role for these anti-mRNAs during infection is unclear.
| S-EPMC247996 | biostudies-other
Project description:We examined population-based surveillance data from the Tennessee Emerging Infections Program to determine whether neighborhood socioeconomic status was associated with influenza hospitalization rates. Hospitalization data collected during October 2007-April 2014 were geocoded (N = 1,743) and linked to neighborhood socioeconomic data. We calculated age-standardized annual incidence rates, relative index of inequality, and concentration curves for socioeconomic variables. Influenza hospitalizations increased with increased percentages of persons who lived in poverty, had female-headed households, lived in crowded households, and lived in population-dense areas. Influenza hospitalizations decreased with increased percentages of persons who were college educated, were employed, and had health insurance. Higher incidence of influenza hospitalization was also associated with lower neighborhood socioeconomic status when data were stratified by race.
| S-EPMC4550146 | biostudies-literature
Project description:Urbanisation and climate change are altering the pattern of California serogroup viruses in North America. As La Crosse virus (LACV) is the most pathogenic of the California serogroup, it is important to identify changes in distribution, transmission and pathogenesis. A scoping review (ScR) was prioritised to summarise the global evidence on LACV. A comprehensive search strategy was used, identified references were screened for relevance and relevant articles were characterised. Each step was conducted by two independent reviewers using pre-tested forms. Analysis identified areas of research saturation and gaps. The ScR included 481 research articles that were mostly journal articles (78.2%) conducted in North America (90.9%) from 1969 to 2016. Most evidence focused on epidemiology (44.9%), virus characteristics (25.8%), transmission conditions (18.7%) and pathogenesis of LACV in hosts (18.3%). Fewer studies evaluated the accuracy of diagnostic tests (8.7%), the efficacy of treatments (3.5%), prevention and control strategies (3.1%), the economic burden of infection (0.6%) and social impact (0.2%) of LACV. None of the literature predicted the impact of climate change on LACV, nor were any cases reported in Canada. These findings are intended to guide research to close knowledge gaps and inform evidence-based decisions surrounding activities for the prevention and control of LACV.
| S-EPMC6518580 | biostudies-literature
Project description: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. RESULTS: Following intraperitoneal inoculation of mice, LACV replicated in various organs before reaching the CNS where it replicates to high titer causing death from neurological disease. The peripheral site where LACV replicates to highest titer is the nasal turbinates, and, presumably, LACV can enter the CNS via the olfactory neurons from nasal olfactory epithelium. The mouse infectious dose50 and lethal dose50 was similar for LACV administered either intranasally or intraperitoneally. LACV was highly infectious for rhesus monkeys and infected 100% of the animals at 10 PFU. However, the infection was asymptomatic, and the monkeys developed a strong neutralizing antibody response. CONCLUSION: In mice, LACV likely gains access to the CNS via the blood stream or via olfactory neurons. The ability to efficiently infect mice intranasally raises the possibility that LACV might use this route to infect its natural hosts. Rhesus monkeys are susceptible to LACV infection and develop strong neutralizing antibody responses after inoculation with as little as 10 PFU. Mice and rhesus monkeys are useful animal models for LACV vaccine immunologic testing although the rhesus monkey model is not optimal.
| S-EPMC2276200 | biostudies-literature
Project description:Eastern equine encephalitis virus (EEEV) is an arbovirus in the family Togaviridae, genus Alphavirus, found in North America and associated with freshwater/hardwood swamps in the Atlantic, Gulf Coast, and Great Lakes regions. EEEV disease in humans is rare but causes substantial illness and death. To investigate the molecular epidemiology and microevolution of EEEV from a fatal case in Alabama, USA, in 2019, we used next-generation sequencing of serum and cerebrospinal fluid (CSF). Phylogenetic inference indicated that the infecting strain may be closely related to isolates from Florida detected during 2010-2014, suggesting potential seeding from Florida. EEEV detected in serum displayed a higher degree of variability with more single-nucleotide variants than that detected in the CSF. These data refine our knowledge of EEEV molecular epidemiologic dynamics in the Gulf Coast region and demonstrate potential quasispecies bottlenecking within the central nervous system of a human host.
| S-EPMC8237905 | biostudies-literature
Project description:The nucleoprotein (NP) of segmented negative-strand RNA viruses such as Orthomyxo-, Arena-, and Bunyaviruses coats the genomic viral RNA and together with the polymerase forms ribonucleoprotein particles (RNPs), which are both the template for replication and transcription and are packaged into new virions. Here we describe the crystal structure of La Crosse Orthobunyavirus NP both RNA free and a tetrameric form with single-stranded RNA bound. La Crosse Orthobunyavirus NP is a largely helical protein with a fold distinct from other bunyavirus genera NPs. It binds 11 RNA nucleotides in the positively charged groove between its two lobes, and hinged N- and C-terminal arms mediate oligomerization, allowing variable protein-protein interface geometry. Oligomerization and RNA binding are mediated by residues conserved in the Orthobunyavirus genus. In the twofold symmetric tetramer, 44 nucleotides bind in a closed ring with sharp bends at the NP-NP interfaces. The RNA is largely inaccessible within a continuous internal groove. Electron microscopy of RNPs released from virions shows them capable of forming a hierarchy of more or less compact irregular helical structures. We discuss how the planar, tetrameric NP-RNA structure might relate to a polar filament that upon supercoiling could be packaged into virions. This work gives insight into the RNA encapsidation and protection function of bunyavirus NP, but also highlights the need for dynamic rearrangements of the RNP to give the polymerase access to the template RNA.
| S-EPMC3645531 | biostudies-literature