The Incidence Risk, Clustering, and Clinical Presentation of La Crosse Virus Infections in the Eastern United States, 2003–2007

Haddow, Andrew D.; Odoi, Agricola

doi:10.1371/journal.pone.0006145

Cited by 98 publications

(105 citation statements)

References 42 publications

(68 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We hypothesize that the differences we see are greater at day 6 due to highly infected flies in the population succumbing to infection by 20 dpi. Additionally, we tested whether decapping restricted another distantly related bunyavirus, LACV, an orthobunyavirus transmitted by mosquitoes to humans (Gerhardt et al 2001;Haddow and Odoi 2009). Control flies challenged with LACV presented with little mortality, while Dcp2-depleted flies succumbed to LACV infection (Fig.…”

Section: Dcp2 Restricts Bunyavirus Infection In Adult Fliesmentioning

confidence: 99%

A genome-wide RNAi screen reveals that mRNA decapping restricts bunyaviral replication by limiting the pools of Dcp2-accessible targets for cap-snatching

et al. 2013

View full text Add to dashboard Cite

Bunyaviruses are an emerging group of medically important viruses, many of which are transmitted from insects to mammals. To identify host factors that impact infection, we performed a genome-wide RNAi screen in Drosophila and identified 131 genes that impacted infection of the mosquito-transmitted bunyavirus Rift Valley fever virus (RVFV). Dcp2, the catalytic component of the mRNA decapping machinery, and two decapping activators, DDX6 and LSM7, were antiviral against disparate bunyaviruses in both insect cells and adult flies. Bunyaviruses 59 cap their mRNAs by ''cap-snatching'' the 59 ends of poorly defined host mRNAs. We found that RVFV cap-snatches the 59 ends of Dcp2 targeted mRNAs, including cell cycle-related genes. Loss of Dcp2 allows increased viral transcription without impacting viral mRNA stability, while ectopic expression of Dcp2 impedes viral transcription. Furthermore, arresting cells in late S/early G2 led to increased Dcp2 mRNA targets and increased RVFV replication. Therefore, RVFV competes for the Dcp2-accessible mRNA pool, which is dynamically regulated and can present a bottleneck for viral replication.

show abstract

Section: Dcp2 Restricts Bunyavirus Infection In Adult Fliesmentioning

confidence: 99%

A genome-wide RNAi screen reveals that mRNA decapping restricts bunyaviral replication by limiting the pools of Dcp2-accessible targets for cap-snatching

et al. 2013

View full text Add to dashboard Cite

show abstract

“…ediatric populations are often more susceptible to virus infections than adults and develop more severe diseases, including virus-mediated neurological diseases (1)(2)(3). A more comprehensive understanding of differences underlying infection in pediatric populations may provide important interventions for treatment of virus infections of the central nervous system (CNS).…”

mentioning

confidence: 99%

“…One virus which induces disease primarily in the pediatric population is mosquito-borne La Crosse virus (LACV), genus Orthobunyavirus, family Bunyaviridae. LACV is a primary cause of pediatric viral encephalitis in the United States, and the expanding vector range makes LACV infections of significant concern for pediatric populations (2,(4)(5)(6)(7). Over 80% of reported neurological disease cases caused by LACV occur in children under 16 and include clinical outcomes ranging from behavioral changes, cognitive defects, and seizures to coma or death (2,6).…”

mentioning

confidence: 99%

Age-Dependent Myeloid Dendritic Cell Responses Mediate Resistance to La Crosse Virus-Induced Neurological Disease

Taylor

Woods

Winkler

et al. 2014

J Virol

View full text Add to dashboard Cite

La Crosse virus (LACV) is the major cause of pediatric viral encephalitis in the United States; however, the mechanisms responsible for age-related susceptibility in the pediatric population are not well understood. Our current studies in a mouse model of LACV infection indicated that differences in myeloid dendritic cell (mDC) responses between weanling and adult mice accounted for susceptibility to LACV-induced neurological disease. We found that type I interferon (IFN) responses were significantly stronger in adult than in weanling mice. Production of these IFNs required both endosomal Toll-like receptors (TLRs) and cytoplasmic RIG-I-like receptors (RLRs). Surprisingly, IFN expression was not dependent on plasmacytoid DCs (pDCs) but rather was dependent on mDCs, which were found in greater number and induced stronger IFN responses in adults than in weanlings. Inhibition of these IFN responses in adults resulted in susceptibility to LACV-induced neurological disease, whereas postinfection treatment with type I IFN provided protection in young mice. These studies provide a definitive mechanism for age-related susceptibility to LACV encephalitis, where mDCs in young mice are insufficiently activated to control peripheral virus replication, thereby allowing virus to persist and eventually cause central nervous system (CNS) disease. IMPORTANCE La Crosse virus (LACV) is the primary cause of pediatric viral encephalitis in the UnitedStates. Although the virus infects both adults and children, over 80% of the reported neurological disease cases are in children. To understand why LACV causes neurological disease primarily in young animals, we used a mouse model where weanling mice, but not adult mice, develop neurological disease following virus infection. We found that an early immune response cell type, myeloid dendritic cells, was critical for protection in adult animals and that these cells were reduced in young animals. Activation of these cells during virus infection or after treatment with type I interferon in young animals provided protection from LACV. Thus, this study demonstrates a reason for susceptibility to LACV infection in young animals and shows that early therapeutic treatment in young animals can prevent neurological disease.

show abstract

“…25 Our data confirm more recent observations that the highest burden of La Crosse virus disease has now shifted to the Appalachian region of West Virginia, Tennessee, North Carolina, and Ohio. [26][27][28] West Nile virus, a flavivirus, is transmitted primarily by Culex mosquitoes, with birds as its natural reservoir. 23,29 This virus now affects children from all regions of the contiguous United States, demonstrating less specificity for particular ecologic and geographic regions than other arboviral etiologies.…”

Section: Discussionmentioning

confidence: 99%

“…For example, spinal cord involvement resulting in acute flaccid paralysis has only rarely been described with La Crosse virus or other orthobunyaviruses but 10 cases of acute flaccid paralysis were reported after La Crosse virus infections in our series. [25][26][27][28][55][56][57][58][59][60] This finding should prompt further investigation to determine if these cases were classified as acute flaccid paralysis due to generalized weakness or true spinal cord infection.…”

Section: Discussionmentioning

confidence: 99%

Neuroinvasive Arboviral Disease in the United States: 2003 to 2012

2014

PEDIATRICS

View full text Add to dashboard Cite

METHODS-We reviewed data reported by state health departments to ArboNET, the national arboviral surveillance system, for 2003 through 2012. Children (<18 years) with neuroinvasive arboviral infections (eg, meningitis, encephalitis, or acute flaccid paralysis) were included. Demographic, clinical syndrome, outcome, geographic, and temporal data were analyzed for all cases.RESULTS-During the study period, 1217 cases and 22 deaths due to pediatric neuroinvasive arboviral infection were reported from the 48 contiguous states. La Crosse virus (665 cases; 55%) and West Nile virus (505 cases; 41%) were the most common etiologies identified. Although less common, Eastern equine encephalitis virus (30 cases; 2%) resulted in 10 pediatric deaths. La Crosse virus primarily affected younger children, whereas West Nile virus was more common in older children and adolescents. West Nile virus disease cases occurred throughout the country, whereas La Crosse and the other arboviruses were more focally distributed.CONCLUSIONS-Neuroinvasive arboviral infections were an important cause of pediatric disease from 2003 through 2012. Differences in the epidemiology and clinical disease result from complex interactions among virus, vector, host, and the environment. Decreasing the morbidity and mortality from these agents depends on vector control, personal protection to reduce mosquito and tick bites, and blood donor screening. Effective surveillance is critical to inform clinicians and

show abstract

The Incidence Risk, Clustering, and Clinical Presentation of La Crosse Virus Infections in the Eastern United States, 2003–2007

Cited by 98 publications

References 42 publications

A genome-wide RNAi screen reveals that mRNA decapping restricts bunyaviral replication by limiting the pools of Dcp2-accessible targets for cap-snatching

A genome-wide RNAi screen reveals that mRNA decapping restricts bunyaviral replication by limiting the pools of Dcp2-accessible targets for cap-snatching

Age-Dependent Myeloid Dendritic Cell Responses Mediate Resistance to La Crosse Virus-Induced Neurological Disease

Neuroinvasive Arboviral Disease in the United States: 2003 to 2012

Contact Info

Product

Resources

About