Type I IFN regulation of early virus establishment in skin muscle is age-dependent [scRNA-Seq]

ABSTRACT: The first site of infection for encephalitic arboviruses is the skin, regulating virus transmission to other tissues within the host. La Crosse virus (LACV), a primary cause of pediatric arboviral encephalitis in North America, initially establishes infection in the panniculus carnosus (PC), the layer of muscle underlying parts of the skin. In the current study, we found an age-related difference in early PC infection. Susceptible young mice, at 3 weeks of age, had substantially higher levels of PC infection compared to resistant adult mice. This was associated with a greater number of macrophages in the skin of adult mice, which contributed to regulation of virus levels in the PC. We also found age-dependent differences in the ability of muscle cells to control early virus infection via the type I interferon (IFN) pathway. Adult PCs had a greater ability to induce ISGs in response to innate immune stimuli and control virus production. Analysis of gene expression showed higher Gpcpd1 and Slc25a25 in adult PC following LACV infection. Depletion of GPCPD1 or SLC25A25 in human muscle cells did not substantially impact virus production alone but did alter the ability of type I IFN to suppress virus production in these cells. Thus, muscle cells of the skin have an age-dependent type I IFN response, which impacts arboviral infection of this tissue.

ORGANISM(S): Mus musculus

PROVIDER: GSE309630 | GEO | 2026/09/30

REPOSITORIES: GEO