Single-cell transcriptome analysis of the in vivo response to viral infection in the cave nectar bat Eonycteris spelaea

Bats are reservoir hosts of many zoonotic viruses with pandemic potential in humans. Here, we<br> utilized single-cell transcriptome sequencing (scRNA-seq) to provide detailed comparative<br> analyses of the immune repertoire and the transcriptional responses in the bat lungs upon in<br> vivo infection with a double-stranded RNA virus, Pteropine orthoreovirus PRV3M. Neutrophils<br> were observed to have basally high IDO1 expression, uniquely amongst mammals currently<br> profiled by scRNA-seq. NK/T cells were the most abundant immune cell type in lung tissue, and<br> included three distinct CD8 + effector T cell populations delineated by the differential expression<br> of KLRB1, GFRA2 and DPP4. We identified NK/T clusters which up-regulated genes involved in<br> T-cell activation and effector function early after viral infection. Alveolar macrophages and<br> classical monocytes were key drivers of antiviral interferon signaling. Infection also resulted in<br> the expansion of a CSF1R + population expressing collagen-like genes, which became the<br> predominant myeloid cell type after infection. This work uncovers novel features relevant to viral<br> disease tolerance in bats, lays a foundation for future in vivo and in vitro experimental<br> investigations, and serves as a key resource for comparative immunology studies across bats<br> and other mammals. This upload is the transcriptome fasta file used for alignment for the dataset.