Abstract
AbstractThe first step in disease pathogenesis for arboviruses is the establishment of infection following vector transmission. For La Crosse virus (LACV), the leading cause of pediatric arboviral encephalitis in North America, and other orthobunyaviruses, the initial course of infection in the skin is not well understood. Using an intradermal (ID) model of LACV infection in mice, we find that the virus infects and replicates nearly exclusively within skin-associated muscle cells of the panniculus carnosus (PC) and not in epidermal or dermal cells like most other arbovirus families. LACV is widely myotropic, infecting distal muscle cells of the peritoneum and heart, with limited infection of draining lymph nodes. Surprisingly, muscle cells are resistant to virus-induced cell death, with long term low levels of virus release progressing through the Golgi apparatus. Thus, skin muscle may be a key cell type for the initial infection and spread of arboviral orthobunyaviruses.
Funder
Division of Intramural Research, National Institute of Allergy and Infectious Diseases
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference48 articles.
1. Beaty, B. J., Hildreth, S. W., Blenden, D. C. & Casals, J. Detection of La Crosse (California encephalitis) virus antigen in mouse skin samples. Am. J. Vet. Res. 43, 684–687 (1982).
2. Bennett, R. S. et al. La Crosse virus infectivity, pathogenesis, and immunogenicity in mice and monkeys. Virol. J. 5, 25 (2008).
3. Lim, P. Y., Behr, M. J., Chadwick, C. M., Shi, P. Y. & Bernard, K. A. Keratinocytes are cell targets of West Nile virus in vivo. J. Virol. 85, 5197–5201 (2011).
4. Byrne, S. N., Halliday, G. M., Johnston, L. J. & King, N. J. Interleukin-1beta but not tumor necrosis factor is involved in West Nile virus-induced Langerhans cell migration from the skin in C57BL/6 mice. J. Invest. Dermatol. 117, 702–709 (2001).
5. Gardner, C. L. et al. Eastern and Venezuelan equine encephalitis viruses differ in their ability to infect dendritic cells and macrophages: impact of altered cell tropism on pathogenesis. J. Virol. 82, 10634–10646 (2008).