Deciphering bat influenza H18N11 infection dynamics in Jamaican fruit bats on a single cell level

Jamaican fruit bats (Artibeus jamaicensis) naturally harbor a wide range of viruses of human relevance. These infections are typically mild in bats, suggesting unique features of their immune system. To better understand the immune response to viral infections in bats, we infected Jamaican fruit bats with the bat-derived influenza A virus H18N11. Using comparative single-cell RNA sequencing, we generated a single-cell atlas of the Jamaican fruit bat intestine and mesentery, the target organs of infection. Gene expression profiling showed that H18N11 infection resulted in a moderate induction of interferon-stimulated genes and transcriptional activation of immune cells. H18N11 infection was prominent in various leukocytes, including macrophages, B cells, and NK/T cells. Confirming these findings, human leukocytes, particularly macrophages, were also susceptible to H18N11, highlighting the zoonotic potential of this virus. Our study provides insight into the virus-host relationship and thus serves as a fundamental resource for further characterization of bat immunology. Jamaican fruit bats were infected with 5x10^5 TCID50 25 µL of either WT H18N11 (n=6) or the NS1-deficient variant delNS1 (n=6). At 3 and 9 dpi 3 animals each were euthanized and the mesentery and intestine of each bat was processed for scRNA-seq. Four uninfected control bats were included.