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

• Published in: Immunity (Cambridge, Mass.) Vol. 55; no. 11; pp. 2187 - 2205.e5
• Main Authors: Gamage, Akshamal M., Chan, Wharton O.Y., Zhu, Feng, Lim, Yan Ting, Long, Sandy, Ahn, Matae, Tan, Chee Wah, Hiang Foo, Randy Jee, Sia, Wan Rong, Lim, Xiao Fang, He, Haopeng, Zhai, Weiwei, Anderson, Danielle E., Sobota, Radoslaw Mikolaj, Dutertre, Charles-Antoine, Wang, Lin-Fa
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.11.2022; Elsevier
• Subjects: Animals; Bats; Chiroptera; Chiroptera - genetics; comparative immunology; disease tolerance; Gene Expression Profiling; Life Sciences; Plant Nectar; respiratory infection; Single-Cell Analysis; single-cell transcriptome sequencing; Transcriptome; viral infection; Virus Diseases; Bats; viral infection; disease tolerance; respiratory infection; single-cell transcriptome sequencing; Chiroptera; comparative immunology
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2022.10.008

Bats are reservoir hosts of many zoonotic viruses with pandemic potential. We utilized single-cell transcriptome sequencing (scRNA-seq) to analyze the immune response in bat lungs upon in vivo infection with a double-stranded RNA virus, Pteropine orthoreovirus PRV3M. Bat neutrophils were distinguished by high basal IDO1 expression. NK cells and T cells were the most abundant immune cells in lung tissue. Three distinct CD8+ effector T cell populations could be delineated by differential expression of KLRB1, GFRA2, and DPP4. Select NK and T clusters increased expression of genes involved in T cell activation and effector function early after viral infection. Alveolar macrophages and classical monocytes drove antiviral interferon signaling. Infection expanded a CSF1R+ population expressing collagen-like genes, which became the predominant myeloid cell type post-infection. This work uncovers features relevant to viral disease tolerance in bats, lays a foundation for future experimental work, and serves as a resource for comparative immunology studies. •scRNAseq analyses of bat lung immune cells upon in vivo viral infection•E. spelaea neutrophils have high basal expression of IDO1•Antiviral responses upon in vivo infection driven primarily by lung myeloid cells•Transcriptional evidence of broad NK and T cells activation early after infection Bats are reservoir hosts of many zoonotic viruses with pandemic potential. Gamage, Chan and Zhu use single-cell RNA sequencing to characterize the immune response in bat lungs upon in vivo infection with Pteropine orthoreovirus and uncover features relevant to immunity and viral disease tolerance in bats, providing a resource for comparative immunology studies.