## 4 Discussion
Virus components might be transmitted into neighboring cells via intercellular pores, as described for measles virus in human airway primary cells [79]. We also observed that EBOV (and also MARV) upregulate NPC1 to very high levels, regardless of the original cellular expression level. Markedly increased NPC1 receptor expression levels were detected in all cells within a well 22 days after EBOV or MARV infection in MoLu Prim, MoBra Prim, and MoKi cells, regardless of individual cells being infected or not. Although only a small number of MoLu Prim cells became infected, theeffect of strong NPC1 upregulation was observed for all cells in a given culture. We hypothesize that a thus far unknown soluble factor(s), secreted from infected cells into the supernatant, is causing the NPC1 expression level changes. Future experiments have to reveal the nature of this phenomenon and how fast the effect of receptor upregulation can be detected after infection with filoviruses. Interestingly, EBOV infection was not increased following NPC1 upregulation, indicating a changing importance of NPC1 during the course of infection. The described correlation between low NPC1 receptor expression levels and EBOV replication rates may have a higher impact in the early course of infection, while later, after general upregulation of NPC1 expression levels, other factors might predominantly influence the efficiency of virus replication in different cell isolates. In humans, high levels of viral replication lead to lysis and necrosis in cells of many organs, including the liver [80], which strongly contributes to the pathogenesis of Ebola virus disease. Interestingly, all primary cells from _M. condylurus_ produced only low or moderate EBOV replication rates compared to human and monkey cells. Translating the low EBOV replication in most of the primary cell isolates from _M. condylurus_ to the potential outcome in the host, one can assume comparable low virus replication rates in the corresponding organs, which could contribute to asymptomatic infections in these microbats. Previous studies of EBOV entry and infection processes in bat cells, predominantly performed in immortalized cell lines [81; 82; 83; 84; 85; 86; 87; 88] have ascertained that cells from a wide variety of bat species support filovirus replication in vitro leading generally to high virus titers [81; 84]. Primary and corresponding immortalized cells of the same organ source (MoKi Prim and MoKi) revealed low and high virus replication rates, respectively. The amplification of EBOV RNA was more than 600-fold higher in immortalized MoKi cell supernatant, confirming the genetic and phenotypic difference of MoKi cells from their in vivo counterparts, while primary cells likely maintain many of the important markers and functions seen in vivo [89; 90; 91]. Human cells (HEK293 and HeLa) and a primary cell isolate from the European microbat _N. notcula_ (NyKi Prim, unlikely to be a reservoir host of EBOV) showed strong CPE with cell death after infection with EBOV, while the first two lost their adherence on days 7 and 10 post-infection, respectively. Plaques and destruction of the cell monolayer after infection with EBOV in _M. condylurus_ cell isolates could only be observed for spontaneously immortalized MoSp Prim Late and for MoBra Prim cells, whereby for the latter, only 20% of the monolayer was affected 16 dpi. All seven other primary cell isolates from _M. condylurus_ did not develop any CPE (MoTra Prim and MoKi Prim) or showed increased cell division rates (MoLu Prim, MoTes Prim, MoLi Prim, MoSp Prim Early, and MoSk Prim) compared to uninfected control cells. [PERSON] et al. hypothesized that viruses are more likely to be cytopathic in non-natural hosts, while viral infections are better tolerated by reservoir hosts even when viral loads are high [92]. In this context, tolerance is defined as the ability to limit the health impact caused by a pathogen [93; 94], so that health and fitness are maintained, despite virus replication.