From nasal to basal: single-cell sequencing of the bursa of Fabricius highlights the IBDV infection mechanism in chickens.

Background: Chickens, important food animals and model organisms, are susceptible to many RNA viruses that invade via the nasal cavity. To determine the nasal entry site of the virus and clarify why avians are susceptible to RNA viruses, infectious bursal disease virus (IBDV) was selected because it is a typical avian RNA virus that infects chickens mainly via the nasal route.

Results: First, we found that IBDV infected the posterior part of the nasal cavity in chickens, which is rich in lymphoid tissue and allows the virus to be easily transferred to the blood. Via the blood circulation, IBDV infected peripheral blood mononuclear cells (PBMCs) and was transferred to the bursa of Fabricius to damage the IgM + B lymphocyte population. Subsequently, the single-cell RNA sequencing (scRNA-seq) results suggested the more detailed response of different bursal cell populations (B cells, epithelial cells, dendritic cells, and fibroblasts) to IBDV. Regarding B cells, IBDV infection greatly decreased the IgM + B cell population but increased the IgA + B cell population in the bursal follicles. In contrast to B cells, bursal epithelial cells, especially basal cells, accumulated a large number of IBDV particles. Furthermore, we found that both innate RNA sensors and interferon-stimulated genes (ISGs) were highly expressed in the IBDV-infected groups, while dicer and ago2 expression was largely blocked by IBDV infection. This result suggests that dicer-related RNA interference (RNAi) might be an effective antiviral strategy for IBDV infection in avian.

Conclusion: Our study not only comprehensively elaborates on the transmission of airborne IBDV via the intranasal route and establishes the main target cell types for productive IBDV infection but also provides sufficient evidence to explain the cellular antiviral mechanism against IBDV infection.