The 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.
La Crosse virus (LACV), a member of the California Serogroup of Orthobunyaviruses, is the primary cause of pediatric arboviral encephalitis in North America. One of the first key steps in arboviral infection is deposition of the virus by the mosquito during blood meal acquisition. Virus can be deposited in the epidermis and dermis of the skin while the mosquito actively probes to locate a capillary to initiate feeding. However, very little is understood