**1. Introduction**

Bats and flying foxes, including large flying foxes (*Pteropus vampyrus*) and variable flying foxes (*P. hypomelanus*) are the mammals belonging to the order *Chiroptera* (hand wing). This order contains 1232 species of bats and flying foxes constituting a more diverse and important order of mammals after rodents. They evolved approximately 52 million years ago [1, 2]. Taxonomically, bats represent approximately 20% of mammalian diversity [3]. They are the real flying mammals and come out for prey in the night time (nocturnal aerial predators). Many species of bats are frugivorous (fruit eating), insectivorous (insect eating), and some feed on blood of other animals (hematophagous). Some species of bats fly long distances during seasonal migration with a speed of 100 miles per hour, making them the fastest mammal (free-flying Brazilian free-tailed bats or *Tadarida brasiliensis*) on earth [4]. Some species of bats fly during night and some are diurnal or crepuscular. Bats are found in all continents, except Antarctica. They live in caves or in other

dark spaces in large groups or colonies and some are solitary in nature. Besides playing a crucial role in maintaining biodiversity or ecological balance through their different roles (insects eating, pollination, and seed dispersal etc.), they remain crucial to researchers due to their strange characteristics and reservoir for different pathogens [2]. For example, the advancing knowledge in bat biology has implicated them (the tropical frugivorous Honduran white bat *Ectophylla alba*) to be studied as a mammalian model for skin carotenoid metabolism [5].

Bats are crucial primary reservoirs for emerging viral infections that can be transferred to humans or cross the species barrier to infect other wild or domesticated animals through spill over [6]. Studies have indicated that they harbor higher numbers of zoonotic viruses per species than rodents [7]. Even they have higher (3.9 times stronger) sympatry than bats and sympatry within a taxonomic order serves as a most crucial host trait for zoonotic virus enrichment [7]. Of note, despite harboring more zoonotic viruses per species than rodents, the total number of zoonotic viruses found in bats (61) are lower than rodents (68) due to double the number of rodent species than bat species. However, bats are the primary host for more virulent viruses than other mammals, including rodents [8]. Before, the emergence of recent virus infections, including severe acute respiratory syndrome (SARS), middle-eastern respiratory syndrome (MERS), Ebola virus infection, and most recent Coronavirus disease 19 (COVID-19) pandemic caused by SARS-CoV-2, MERS-CoV, Ebola virus or *Zaire Ebolavirus* (three different species of Ebola viruses have been found in greater long-fingered bat (*Miniopterus inflatus* or *M. inflatus*) in Liberia's Sanniquellie-Mahn District that borders to Guinea and insect-eating bat, *M. schreibersii*), and SARS-CoV-2, the studies of natural histories of bats, their importance as primary reservoirs for different zoonotic viral diseases have been largely underappreciated, underrated, and underfunded [9–12]. Although, they (vampire bats or *Desmodus rotundus murinua* found only in the Latin America) were considered for their role in the rabies transmission called vampire bat rabies as suggested first in 1959 [13–16].

Fruit bats, including *Hypsignathus monstrosus*, *Epomops franqueti*, and *Myonycteris torquate* have also been suggested as potential reservoirs for *Zaire Ebolavirus* [12, 17]. In addition to these zoonotic viral infections, bats also serve as potential reservoirs for other viruses responsible for infections in humans that include Nipah, Hendra, Marburg, Hepadna (able to infect human hepatocytes), and Lyssa viruses etc. Thus, different viruses of 23 virus families have been detected in different bat species (196) in 69 countries all over the world [3, 18]. The mortality among bats due to bacterial or viral infection has been the least observed cause of death [19]. In comparison to humans, where 7% of the genome encodes for the immune or related genes (1562 immune genes recorded in humans as of 1st October 2004 by the immunogenetic related information source or IRIS), only less than 4% of the bat (Australian flying fox or *Pteropus alecto*) genome encodes from immune related genes (about 500) [20, 21]. For example, Jamaican fruit bat or *Artibeus jamaicensis* has 466 immune-related genes (IRGs) and the Egyptian Rousette bat (*Rousettus aegyptiacus*), a common fruit bat species has 407 or 2.75% IRGs of their total genome [22, 23]. Thus, either bats have lower numbers of IRGs as compared to humans or we need further studies in other potential bat species harboring potent virus pathogens that can infect humans directly or indirectly through secondary reservoir hosts.

Also, Panamanian Seba's short-tailed bats (*Carollia perspicillata*), a widely distributed neotropical species shows individual and population-specific diversity in their major-histocompatibility complex 1 or MHC-1 genes with an unique genotype in each individual comparable to passerine or perching or singing birds [24]. The MHC-II diversity is also correlated with the geographic origin and population

*Learning from Bats to Escape from Potent or Severe Viral Infections DOI: http://dx.doi.org/10.5772/intechopen.98916*

admixture in *Carollia perspicillata* and *Molossus molossus*, and in *Desmodus rotundus* MHC-II DRB gene diversity depends on the environment only [25]. The MHC diversity in bats may impact their defense against different reservoir viruses inducing resistance against them and providing an opportunity or a perfect animal niche for the virus evolution that may infect other hosts, including humans severely [24]. The Egyptian Rousette or fruit bat does not support the productive growth or replication of the Nipah virus [26]. No seroconversion against Nipah virus glycoprotein has been reported in these bats. Hence, only specific bat species serve as potential reservoirs for Nipah viruses. This may be true for other viruses too. The *in vitro* study based on bat cells (RoNi/7.1 (*Rousettus aegyptiacus*) and PaKiT01 (*P. alecto*) cells) lines has indicated the enhanced interferon (IFN)-mediated antiviral immune response generation of either constitutive or induced form that allows a rapid cell to cell virus transmission rate (β) within the host [27]. The IFN-induced antiviral state protects live cells from apoptotic or other forms of cell death *in vitro* that (the *in vitro* epidemic or extended life of the cells) enhances the probability of developing and establishing a long-term persistent infection [27]. This phenotype of infection and associated host-pathogen interaction response is absent in Vero cells (a cell line derived from the kidneys of African green monkeys) due to the genetic defect in the IFN production [27, 28]. Hence, viruses evolved in bats as reservoirs have an increased IFN capabilities that helps to achieve a rapid within-host transmission rates without inducing clinical symptoms of the disease. Thus these rapidly reproducing viruses in bats may become more virulence upon spillover to hosts, including humans lacking similar immune capabilities like bats. Hence, understanding the bat immune function or response becomes crucial to understand. The present chapter describes the immunological aspects or features of bats preparing them to harbor a wide range of viruses without severe disease causing mortality.
