la crosse virus
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Author(s):  
Durbadal Ojha ◽  
Clayton W. Winkler ◽  
Jacqueline M. Leung ◽  
Tyson A. Woods ◽  
Catherine Z. Chen ◽  
...  
Keyword(s):  

2021 ◽  
Author(s):  
Benoit Arragain ◽  
Quentin Durieux Trouilleton ◽  
Florence Baudin ◽  
Stephen Cusack ◽  
Guy Schoehn ◽  
...  

Segmented negative-strand RNA bunyaviruses encode a multi-functional polymerase that performs genome replication and transcription. Here, we establish conditions for in vitro activity of La Crosse virus polymerase and visualize by cryo-electron microscopy its conformational dynamics, unveiling the precise molecular mechanics underlying its essential activities. Replication initiation is coupled to distal duplex promoter formation, endonuclease movement, prime-and-realign loop extension and closure of the polymerase core that direct the template towards the active site. Transcription initiation depends on C-terminal region closure and endonuclease movements that firstly prompt primer cleavage and secondly promote primer entry in the active site. Product realignment after priming, observed in replication and transcription, is triggered by the prime-and-realign loop. Switch to elongation results in polymerase reorganization and core region opening to facilitate template-product duplex formation in the active site cavity. The detailed uncovered mechanics will be crucial for future design of antivirals counteracting bunyaviral life-threatening pathogens.


Author(s):  
Grace M. Vahey ◽  
Nicole P. Lindsey ◽  
J. Erin Staples ◽  
Susan L. Hills

La Crosse virus (LACV) is an arthropod-borne virus that can cause a nonspecific febrile illness, meningitis, or encephalitis. We reviewed U.S. LACV surveillance data for 2003–2019, including human disease cases and nonhuman infections. Overall, 318 counties in 27 states, principally in the Great Lakes, mid-Atlantic, and southeastern regions, reported LACV activity. A total of 1,281 human LACV disease cases were reported, including 1,183 (92%) neuroinvasive disease cases. The median age of cases was 8 years (range: 1 month–95 years); 1,130 (88%) were aged < 18 years, and 754 (59%) were male. The most common clinical syndromes were encephalitis (N = 960; 75%) and meningitis (N = 219, 17%). The case fatality rate was 1% (N = 15). A median of 74 cases (range: 35–130) was reported per year. The average annual national incidence of neuroinvasive disease cases was 0.02 per 100,000 persons. West Virginia, North Carolina, Tennessee, and Ohio had the highest average annual state incidences (0.16–0.61 per 100,000), accounting for 80% (N = 1,030) of cases. No animal LACV infections were reported. Nine states reported LACV-positive mosquito pools, including three states with no reported human disease cases. La Crosse virus is the most common cause of pediatric neuroinvasive arboviral disease in the United States. However, surveillance data likely underestimate LACV disease incidence. Healthcare providers should consider LACV disease in patients, especially children, with febrile illness, meningitis, or encephalitis in areas where the virus circulates and advise their patients on ways to prevent mosquito bites.


2021 ◽  
Vol 46 (1) ◽  
Author(s):  
Tuamami T. Tamini ◽  
Brian D. Byrd ◽  
J. Alan Goggins ◽  
Charles B. Sither ◽  
Laura White ◽  
...  

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Rahul Basu ◽  
Vinod Nair ◽  
Clayton W. Winkler ◽  
Tyson A. Woods ◽  
Iain D. C. Fraser ◽  
...  

Abstract Background A key factor in the development of viral encephalitis is a virus crossing the blood-brain barrier (BBB). We have previously shown that age-related susceptibility of mice to the La Crosse virus (LACV), the leading cause of pediatric arbovirus encephalitis in the USA, was associated with the ability of the virus to cross the BBB. LACV infection in weanling mice (aged around 3 weeks) results in vascular leakage in the olfactory bulb/tract (OB/OT) region of the brain, which is not observed in adult mice aged > 6–8 weeks. Thus, we studied age-specific differences in the response of brain capillary endothelial cells (BCECs) to LACV infection. Methods To examine mechanisms of LACV-induced BBB breakdown and infection of the CNS, we analyzed BCECs directly isolated from weanling and adult mice as well as established a model where these cells were infected in vitro and cultured for a short period to determine susceptibility to virus infection and cell death. Additionally, we utilized correlative light electron microscopy (CLEM) to examine whether changes in cell morphology and function were also observed in BCECs in vivo. Results BCECs from weanling, but not adult mice, had detectable infection after several days in culture when taken ex vivo from infected mice suggesting that these cells could be infected in vitro. Further analysis of BCECs from uninfected mice, infected in vitro, showed that weanling BCECs were more susceptible to virus infection than adult BCECs, with higher levels of infected cells, released virus as well as cytopathic effects (CPE) and cell death. Although direct LACV infection is not detected in the weanling BCECs, CLEM analysis of brain tissue from weanling mice indicated that LACV infection induced significant cerebrovascular damage which allowed virus-sized particles to enter the brain parenchyma. Conclusions These findings indicate that BCECs isolated from adult and weanling mice have differential viral load, infectivity, and susceptibility to LACV. These age-related differences in susceptibility may strongly influence LACV-induced BBB leakage and neurovascular damage allowing virus invasion of the CNS and the development of neurological disease.


PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249811
Author(s):  
Cameron Cook ◽  
Annastashia Blesi ◽  
Samantha Brozak ◽  
Suzanne Lenhart ◽  
Hanna Reed ◽  
...  

In Appalachia, La Crosse virus (LACV) is a leading pediatric arbovirus and public health concern for children under 16 years. LACV is transmitted via the bite of an infected Aedes mosquito. Thus, it is imperative to understand the dynamics of the local vector population in order to assess risk and transmission. Using entomological data collected from Knox County, Tennessee in 2013, we formulate an environmentally-driven system of ordinary differential equations to model mosquito population dynamics over a single season. Further, we include infected compartments to represent LACV transmission within the mosquito population. Findings suggest that the model, with dependence on degree days and accumulated precipitation, can closely describe field data. This model confirms the need to include these environmental variables when planning control strategies.


Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 400
Author(s):  
Sarah N. Wilson ◽  
Krisangel López ◽  
Sheryl Coutermash-Ott ◽  
Dawn I. Auguste ◽  
Danielle L. Porier ◽  
...  

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.


Author(s):  
Cody W Koloski ◽  
Ivan Drahun ◽  
Bryan J Cassone

Abstract Native to the Eastern United States and Eastern Canada, Aedes triseriatus (eastern tree hole mosquito) is an important vector of La Crosse virus and dog heartworm. Although its range has been well characterized in the United States, few studies have surveyed its distribution within Canada. In this study, mosquitoes were collected from a variety of urban and rural communities throughout Manitoba, Canada between the years of 2018 and 2020. Aedes triseriatus was identified and confirmed molecularly to be present in 13 communities. This includes localities that expand the species known distribution to new northern and western areas, and suggests that past surveillance efforts have not been comprehensive or environmental factors have caused this mosquito species to be present in areas in which it was not found previously. As Canada is showing signs of a changing climate, this may be driving the broader occurrence of Ae. triseriatus.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Emma Stump ◽  
Lauren M. Childs ◽  
Melody Walker

Abstract Background Mosquitoes are vectors for diseases such as dengue, malaria and La Crosse virus that significantly impact the human population. When multiple mosquito species are present, the competition between species may alter population dynamics as well as disease spread. Two mosquito species, Aedes albopictus and Aedes triseriatus, both inhabit areas where La Crosse virus is found. Infection of Aedes albopictus by the parasite Ascogregarina taiwanensis and Aedes triseriatus by the parasite Ascogregarina barretti can decrease a mosquito’s fitness, respectively. In particular, the decrease in fitness of Aedes albopictus occurs through the impact of Ascogregarina taiwanensis on female fecundity, larval development rate, and larval mortality and may impact its initial competitive advantage over Aedes triseriatus during invasion. Methods We examine the effects of parasitism of gregarine parasites on Aedes albopictus and triseriatus population dynamics and competition with a focus on when Aedes albopictus is new to an area. We build a compartmental model including competition between Aedes albopictus and triseriatus while under parasitism of the gregarine parasites. Using parameters based on the literature, we simulate the dynamics and analyze the equilibrium population proportion of the two species. We consider the presence of both parasites and potential dilution effects. Results We show that increased levels of parasitism in Aedes albopictus will decrease the initial competitive advantage of the species over Aedes triseriatus and increase the survivorship of Aedes triseriatus. We find Aedes albopictus is better able to invade when there is more extreme parasitism of Aedes triseriatus. Furthermore, although the transient dynamics differ, dilution of the parasite density through uptake by both species does not alter the equilibrium population sizes of either species. Conclusions Mosquito population dynamics are affected by many factors, such as abiotic factors (e.g. temperature and humidity) and competition between mosquito species. This is especially true when multiple mosquito species are vying to live in the same area. Knowledge of how population dynamics are affected by gregarine parasites among competing species can inform future mosquito control efforts and help prevent the spread of vector-borne disease.


2021 ◽  
Author(s):  
Emma Stump ◽  
Lauren M Childs ◽  
Melody Walker

Abstract Background: Mosquitoes are vectors for diseases that significantly impact the human population such as dengue, malaria and La Crosse virus. When multiple mosquito species are present, the competition between species may alter population dynamics as well as disease spread. Two mosquito species, Aedes albopictus and Aedes triseriatus, both inhabit areas where La Crosse virus is found. Infection of Aedes albopictus by the parasite Ascogregarina taiwanensis and Aedes triseriatus by the parasite Ascogregarina barretti can decrease a mosquito’s fitness, respectively. In particular, the decrease in fitness of Aedes albopictus occurs through the impact of Ascogregarina taiwanensis on female fecundity, larval development rate, and larval mortality and may impact its initial competitive advantage over Aedes triseriatus during invasion.Methods: We examine the effects of parasitism of gregarine parasites on Aedes albopictus and triseriatus population dynamics and competition with a focus on when Aedes albopictus is new to an area. We build a compartmental model including competition between Aedes albopictus and triseriatus while under parasitism of the gregarine parasites. Using parameters based on literature, we simulate the dynamics and analyze the equilibrium population proportion of the two species. We consider the presence of both parasites and potential dilution effects.Results: We show that increased levels of parasitism in Aedes albopictus will decrease the initial competitive advantage of the species over Aedes triseriatus and increase the survivorship of Aedes triseriatus. We find Aedes albopictus is better able to invade when there is more extreme parasitism of Aedes triseriatus. Furthermore, although the transient dynamics differ, dilution of the parasite density through uptake by both species does not alter the equilibrium population sizes of either species.Conclusions: Mosquito population dynamics are affected by many factors, such as abiotic factors (e.g. temperature and humidity) and competition between mosquito species. This is especially true when multiple mosquito species are vying to live in the same area. Knowledge of how population dynamics are affected by gregarine parasites among competing species can inform future mosquito control efforts and help prevent the spread of vector-borne disease.


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