Human macrophages infected with Egyptian rousette bat-isolated Marburg virus display inter-individual susceptibility and antiviral responsiveness

Ivet A. Yordanova¹, Angelika Lander¹, Annette Wahlbrink¹, Jonathan S. Towner², César G. Albariño², Lay Teng Ang³, Joseph B. Prescott^1*

¹Centre for Biological Threats and Special Pathogens, Robert Koch Institute, 13353 Berlin, Germany

² Viral Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA

³ Stanford Institute for Stem Cell Biology & Regenerative Medicine, Stanford University, Stanford, CA 94305 USA

^* Corresponding author

Abstract Marburg virus (MARV) is a highly-pathogenic filovirus and a causative agent of sporadic zoonotic viral hemorrhagic fever outbreaks with high case fatality rates. In humans, filoviruses like MARV and Zaire Ebola virus (EBOV) target, among others, innate immune cells like dendritic cells and macrophages (Mcs). Filovirus-infected dendritic cells display impaired maturation and antigen presentation, while Mcs become hyper-activated and secrete proinflammatory cytokines and chemokines. Our current understanding of human macrophage responses to MARV remains limited. Here, we used human monocyte-derived macrophages (moMcs) to address how their phenotype, transcriptional profile and protein expression change upon an in vitro infection with a bat isolate of MARV. Confirming its tropism for macrophages, we show that MARV induces notable shifts in their transcription distinct from responses induced by lipopolysaccharide (LPS), marked by upregulated gene expression of several chemokines, type I interferons and IFN-stimulated genes. MARV infection also elicited pronounced inter-individually different transcriptional programs in moMcs, the induction of Wnt signaling-associated genes and the downregulation of multiple biological processes and molecular pathways.