TY - JOUR
T1 - Skin muscle is the initial site of viral replication for arboviral bunyavirus infection
AU - Schneider, Christine A.
AU - Leung, Jacqueline M.
AU - Valenzuela-Leon, Paola Carolina
AU - Golviznina, Natalya A.
AU - Toso, Erik A.
AU - Bosnakovski, Darko
AU - Kyba, Michael
AU - Calvo, Eric
AU - Peterson, Karin E.
N1 - Publisher Copyright:
© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024.
PY - 2024/12
Y1 - 2024/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-024-45304-0
DO - 10.1038/s41467-024-45304-0
M3 - Article
C2 - 38321047
AN - SCOPUS:85184427155
SN - 2041-1723
VL - 15
JO - Nature communications
JF - Nature communications
IS - 1
ER -