1.5.1 Zoonotic diseases and pathogens
The term zoonoses describes infectious diseases which can be transmitted from animals to humans (zooanthroponose) or vice versa (anthropozoonose) and are caused by viruses, bacteria, parasites or prions (WHO 2020). About 61% of human infections and 75% of the emerging diseases are caused by zoonotic pathogens (Taylor et al. 2001). It is assumed that
1.5.2 Bats as reservoir hosts of zoonotic viruses
Bats and flying foxes are the natural reservoir hosts for many zoonotic viruses, especially for emerging and re-emerging viruses, hence playing an important role in virus transmission (Calisher et al. 2006). As a typical feature of reservoir hosts, virus-harboring bats develop no or only mild clinical signs (Mandl et al. 2015). A variety of unique characteristics make bats advantageous hosts for viruses and other pathogens. Bats are geographically widespread and due to their ability to fly, they can cover quite large distances. During active flight, their body temperature and metabolism are increased speculating an effect on the immune system such as DNA damage repair and a reduced sensing of exogenous and endogenous DNA to avoid inflammatory responses induced by an accumulation of cytosolic self-DNA (Zhang et al. 2013;
O'Shea et al. 2014; Ahn et al. 2016; Xie et al. 2018). Given that bats show a high tolerance to viral infections in form of reduced clinical illness due to a reduced inflammation, a from other mammals deviating innate immune system is discussed (Banerjee et al. 2017; Pavlovich et al.
2018; Banerjee et al. 2020). Their long lifespan enables a long persistence of a chronic infection (Luis et al. 2013). During torpor and/or hibernation the bat’s energy metabolism is minimized leading to a reduced virus replication what in turn dampens the risks of clinical disease for bats. In return, the immune system of hibernating bats is also almost shut down supporting the persistence of the virus infection (Sulkin 1974; Calisher et al. 2006). In addition, their colonial behavior including roosting results in a rapid intra- and interspecies dissemination of viruses (Luis et al. 2013).
Until 2006, 66 virus species belonging to the genera Alpha-, Flavi-, Henipa-, Lyssa-, Orbi-, Orthoreo-, Phlebo-, Orthobunya- and Orthorubulavirus were detected in bat samples (Calisher et al. 2006). These include e.g. rabies virus that was found in many different bat species worldwide, or severe acute respiratory syndrome coronavirus (SARS-CoV) being isolated from Rhinolophus bats (Piraccini 2016; Sun 2019). Flying foxes of the genus Pteropus were identified as reservoir hosts of the henipaviruses HeV, NiV and Cedar virus (Hooper et al.
2000; Marsh et al. 2012; Roberts et al. 2017; Tsang 2020). Further, in numerous bat species the chikungunya and rift valley fever virus which are both transmitted by mosquitos, as well as the Japanese encephalitis virus were detected (Fagre et al. 2019). In a more recent study, bats might also be revealed as reservoir hosts for polyomaviruses (Tan et al. 2020). In addition, the circulation of the Bombali ebolavirus belonging to the genus Ebolavirus within free-tailed bats was reported (Goldstein et al. 2018; Forbes et al. 2019).
The amount of novel viruses detected in bats increased significantly during the last years.
However, in most cases no virus isolate but viral RNA was derived from the bat samples. The detection of several highly diverse paramyxoviruses in African fruit bats might indicate that most paramyxoviruses have their origin in bats (Drexler et al. 2009; Baker et al. 2012; Drexler et al. 2012; Baker et al. 2013).
1.5.3 Bat-derived mumps virus
In 2009, the discovery of the RNA of a MuV-related virus (BatPV/Epo_spe/AR1/DCR/2009, GenBank accession no.: HQ660095.1, bat-derived MuV, batMuV) in the spleen of an African flying fox of the genus Epomophorus in the Democratic Republic of Congo queried the assumption that humans are the only reservoir host for MuVs (Drexler et al. 2012). The batMuV is phylogenetically closely related to human MuVs (hMuV) as shown by Bayesian interference.
Its genome is comprised of 15,378 nt and shares an identical organization with the viral genome of hMuVs. Further, the aa sequence homology for all proteins of human and bat-derived MuVs is noticeable high and ranges between maximal 72.6% identity for the P proteins and 94.2% for the L proteins. One exception is the SH protein which is also hypervariable among hMuV strains and shares only 38.6% similarity between hMuV and batMuV (Drexler et al. 2012). A serological relatedness has been demonstrated by the reactivity of bat sera against hMuV as well as by the cross-reactivity of neutralizing antibodies directed against hMuV strains that were capable of detecting and neutralizing batMuV (Drexler et al. 2012; Kruger et al. 2015;
Katoh et al. 2016; Kruger et al. 2016; Beaty et al. 2017; Kruger et al. 2018). Due to the cross-reactivity, it is impossible to distinguish between batMuV and hMuV only on the basis of serological tests. The sequencing of the SH protein would provide information required to differentiate between hMuV and batMuV; however, RNA isolation and sequencing are not performed as part of routine diagnostics. Thus, it is not known whether humans have already been infected with batMuV.
First investigations on the biological characterization of batMuV focused on the surface glycoproteins F and HN. Transfection studies revealed that batMuV F and HN are able to mediate cell-to-cell fusion in cell lines originated from human, bat, non-human primate or rodent species. hMuV and batMuV F and HN proteins can interact with each other to mediate fusions underlining the close relatedness between these viruses. A similar functionality of human and bat-derived MuV glycoproteins was further proven by showing that batMuV HN utilizes sialic acids for binding to target cells and exhibits neuraminidase activity similar to its human counterpart (Kruger et al. 2015). In a follow-up study, recombinant chimeric MuVs in