Geographically persistent clusters of La Crosse virus disease in the Appalachian region of the United States from 2003 to 2021

Abstract

La Crosse virus (LACV) is a mosquito-borne pathogen that causes more pediatric neuroinvasive disease than any other arbovirus in the United States. The geographic focus of reported LACV neuroinvasive disease (LACV-ND) expanded from the Midwest into Appalachia in the 1990s, and most cases have been reported from a few high-risk foci since then. Here, we used publicly available human disease data to investigate changes in the distribution of geographic LACV-ND clusters between 2003 and 2021 and to investigate socioeconomic and demographic predictors of county-level disease risk in states with persistent clusters. We used spatial scan statistics to identify high-risk clusters from 2003–2021 and a generalized linear mixed model to identify socioeconomic and demographic predictors of disease risk. The distribution of LACV-ND clusters was consistent during the study period, with an intermittent cluster in the upper Midwest and three persistent clusters in Appalachia that included counties in east Tennessee / western North Carolina, West Virginia, and Ohio. In those states, county-level cumulative incidence was higher when more of the population was white and when median household income was lower. Public health officials should target efforts to reduce LACV-ND incidence in areas with consistent high risks.

The La Crosse virus class II fusion glycoproteinijloop contributes to infectivity and cholesterol-dependent entry

“…La Crosse virus (LACV) is an emerging neuroinvasive arbovirus that has been a major cause of pediatric encephalitis throughout the United States, with persistent high-risk clusters of cases in the Midwest and Appalachian regions (12). Here, we used the structural similarities of the CHIKV E1 and the LACV Gc class II fusion glycoproteins to hypothesize the importance of the ij loop for cholesterol-dependent entry and infectivity in vitro and in vivo .…”

“…LACV is transmitted by the Aedes species of mosquito (10,11) and can cause severe encephalitis, as it is the most common cause of pediatric neuroinvasive arboviral disease in children in the United States (12)(13)(14)(15). However, while our knowledge of bunyavirus entry is limited, we can use what we know from alphaviruses and flaviviruses to infer how bunyaviruses establish infections.…”

“…The S segment encodes for the nucleoprotein (N) and NSs protein (4, 8), the M segment encodes for the viral glycoproteins Gn and Gc (7, 9) and nonstructural protein NSm, and the L segment encodes for the viral RNA dependent RNA polymerase (4). LACV is transmitted by the Aedes species of mosquito (10, 11) and can cause severe encephalitis, as it is the most common cause of pediatric neuroinvasive arboviral disease in children in the United States (12–15).…”

La Crosse virus reassortants highlight genomic determinants of infection and pathogenesis

“…La Crosse virus (LACV) is negative-sense segmented RNA orthobunyavirus transmitted to humans via infected mosquito bite (4) (5). LACV is endemic to the United States and is mainly found in the East North Central and Appalachian regions (6). A member of the California serogroup of orthobunyaviruses, it is related to other neuroinvasive human viruses found worldwide, including Jamestown Canyon virus, Inkoo virus and Tahyna virus (7).…”

Evaluating the mosquito vector range for two orthobunyaviruses: Oya virus and Ebinur Lake Virus

“…Multiple viruses belonging to the Simbu and Bunyawera serogroups have been found in various mosquito species, including Culex spp., Aedes spp., and Anopheles spp [4,5,6]. Members of the family Peribunyaviridae can introduce illnesses in vertebrates, with encephalitis caused by the Oropouche virus (OROV) and La Crosse virus (LACV) affecting humans [7,8]. Additionally, ruminants are at risk of abortions and teratogenic effects from Bunyamwera virus (BUNV) and Cache Valley virus (CVV) [9,10].…”