**4. Coevolution between bats and viruses**

Sierra Leone. On April 2015, the Ebolavirus outbreaks had already resulted in more than 10,880 deaths among 26,277 cases [38]. On March 2016, WHO reported a total 11,323 deaths among 28,646 cases, indicating a decrease in the spreading of the virus in human. There is no direct evidence that bat is the reservoir for ebolavirus-inducing disease in humans. Yet, Ebola-related virus were found in tissues of several bats (the hammer-headed fruit bat: *Hypsignathus monstrosus*; the Franquet's epauletted bat: *Epomops franqueti*; and the little collared fruit bat: *Myonycteris torquata*) [9], and experimental infections of the Angola free-tail bat (*Mops condylurus*), little free-tail bat (*Chaerephon pumilus*), and Wahlberg's epauletted fruit bat (*Epomophorus wahlbergi*) with a Zaire strain of Ebola virus led to viral replication in these bats [39]. Widespread infection of cave-dwelling bats by Crimean Congo hemorrhagic fever virus (CCHFV) has also been reported, suggesting a role of bats in the life cycle and

It is generally admitted that bats are a source of high viral diversity that may directly or indirectly (following genomic recombination, gene mutations, gene duplication loss/gain) cause a new outbreak. Since the past 20 years, a massive international effort was devoted to the identification of viruses in different families of bats. As shown in **Figure 2**, the total number of bat-associated sequences in GenBank has grown exponentially in the last 20 years. A review of articles referring to bat-borne viruses (**Figure 3**) indicates that rabbies (55,000 persons infected each year, case fatality nearly 100%) is the most prominent topic with 2792 articles (33%). Surprisingly, as shown in **Figure 3A**, the virus family that rank second is *Coronaviridae* with 2622 articles (31%), while the total number of cases accumulated the different episodes remains relatively low (cumulative cases about 8000 individuals; mean case fatality around 10%). Moreover, the number of scientific report about virus family indicates that Coronavirus rank first in terms of publications when MeSH terms concern viruses and

**Figure 2.** Data increase of bat-associated viruses during the past 20 years. This figure illustrates the total number of sequences of bat-associated viruses available in GenBank according to the database of bat-associated viruses (http:// www.mgc.ac.cn/cgi-bin/DBatVir/main.cgi). During the same period (1997–2017), the total number of publications about

bat-associated viruses in PubMed increased from 2 to 367 publications/year.

geographic dispersal of this virus [40].

118 Bats

The biological interaction of viruses and their hosts is usually antagonistic, with a delicate balance of actions and counteractions between host immune system and virus escape mechanisms. Parasite-induced reduction in host fitness enhances selection for host resistance mechanisms. On the other hand, novel host defenses increase selection on the parasite. A tight genetic interaction between hosts and pathogens can lead to ongoing host-parasite coevolution, defined as the reciprocal evolution of interacting hosts and parasites [42]. The antagonistic coevolutionary arms race of parasite infectivity and host resistance leads to adaptations and counteradaptations in the coevolution and also has a central role in the evolution of host-parasite relationships in the microbial world [43]. A key consequence of coevolution is the impact on genetic diversity of host and parasite populations. The host-parasite coevolution is widely assumed to have a major influence on biological evolution by imposing a high selective pressure on both host and virus. Selected traits, genes involved, and the underlying selection dynamics represent central topics of interest for understanding host-parasite coevolution [44].

response between bat species against the same virus. Important differences in percentage of seroconversion against European bat lyssavirus type 1 (EBLV-1) were observed between two species from two distinct families: *Rhinolophus ferrumequinum* (*Rhinolophidae*) and *Myotis myotis* (*Vespertilionidae*). The percentage of seropositive *Rhinolophus ferrumequinum* was much lower than that of *Myotis myotis* [45], suggesting differential rates of seroconversion. Turmelle et al. [52] reported that significant differences in seroconversion rates were found among bats depending on whether they had previously been infected, suggesting that long-term repeated infections of bats might confer significant immunological memory and reduced susceptibility to rabies infection. Immune competence in bats can vary with body condition (via nutritional status and stress) and reproductive activity and, as a consequence, can lead to a lower rabies

Bats, Bat-Borne Viruses, and Environmental Changes http://dx.doi.org/10.5772/intechopen.74377 121

Bats are considered major hosts for alphacoronaviruses and betacoronaviruses and they play an important role as the gene source in the evolution of these two genera of coronavirus [53]. Most, if not all, alphacoronaviruses and betacoronaviruses found in mammals are evolutionally linked to ancestral bat coronaviruses [54]. Different species of *Rhinolophus* bats in China carry genetically diverse SARS-like coronaviruses, some of which are direct ancestors of SARS-CoV and hence have the potential to cause direct interspecies transmission to humans [54]. A largescale study conducted worldwide on 282 bat species from 12 families demonstrated the presence of coronaviruses on 8.6% of bats whereas the ratio was only 0.2% on non-bat species [36]. A relationship between viral richness and bat species richness was demonstrated, suggesting that the diversity of bat CoVs has been driven primarily by host ecology [36, 41]. Preferred association between viral subclade and bat family was also observed. Bat-borne Dependoparvoviruses are also suspected to be the ancestral origin of adeno-associated virus (AAVs) in mammals [55]. Similarly, bats are the primary reservoir for 15 of 17 species of lyssaviruses [56]. Lyssaviruses

may have evolved in bats long before the emergence of carnivoran rabies [6, 57].

Dissemination of viruses among bat populations is a complex system affected by many traits of the seasonal bats life. Seasonality and environmental conditions determine birthing periods, migrations, gregarious behavior, and torpor of each bat species. Each one may affect population density, rates of contact between individuals, and consequently the basic reproductive

) is an important parameter in the dynamic of diseases and is the average number of new infections that would arise from a single infectious host introduced into a population of susceptible hosts [58]. Understanding how pathogens spread within their host populations is a key factor in epidemiology. It is especially difficult to study the vertical transmission of viruses in bats. Bats are very sensitive to disturbances and environmental changes, especially during breeding period. A disturbance in a maternity colony can produce an important mortality in newborn bats that may impact in the demography of population. The per capita transmission rate depends on the infectivity of the virus, the susceptibility of the host, but also on the contact

) and virus transmission between species. The basic reproductive number

seroprevalence between or within bat species.

number of virus (R0

(R0

**5. Intra and interspecific transmission of bat viruses**

The evolution of bats is a very successful singular history among mammals that have produced an enormous diversity of species with high mobility and great longevity adapted to a great spectrum of environments [42]. Bats host more zoonotic viruses and more total viruses per species than rodents, despite the fact that there is a lot more known species of rodents [45]. Furthermore, bats harbor a significantly higher proportion of zoonotic viruses than all other mammalian orders [46]. The antagonistic coevolutionary arms race of parasite infectivity and host resistance leads to adaptations and counteradaptations in the coevolution and also has a central role in the evolution of host-parasite relationships in the microbial world [47]. The origin of bats is estimated at about 64 million years ago or following the Cretaceous-Tertiary boundary [48]. The millions of years of bat evolution might have given rise to the coevolution processes between host and pathogen. The antagonistic coevolution between infectivity of viruses and resistance of bats is still poorly known. The ability of bats to harbor extremely lethal viruses for humans without apparent morbidity and mortality has long been discussed. The lack of abnormal ethology observed in virus-infected bats may be due at the selection of resistance mechanisms.

The evolution of flight in bats has been accompanied by genetic changes to their immune systems to accommodate high metabolic rates. The increased metabolism and higher body temperatures of bats during flight might have enhanced their immune system, increasing resistance and thus increase the diversity of viruses they host [2, 49]. This increase of metabolic rate in bats is estimated to be 15- to 16-fold, when it is only sevenfold for running rodents and twofold for birds [2]. Marburg, Angola, Ebola, and Makona-WPGC07 viruses were shown to efficiently replicate at flight temperature of bats, i.e. 37 and 41°C, indicating that flight-related temporal elevation in temperature does not affect filovirus replication [50]. Furthermore, many bat species display a daily torpor with decrease of body temperature which might be a virus-resistance strategy, interfering with optimal virus replication [2]. Bats also display a unique interferon system (IFNs) that may explain the ability of bats to coexist with viruses [51]. Mammals have a large IFN locus comprising a family of IFN-α genes expressed following infection. Conversely, bats display a contracted IFN locus with only three functional IFN-α, but constitutively and permanently expressed [51]. This constitutive expression could turn to be a highly effective system for controlling viral replication and explain the resistance of bats to viruses. Differences have also been observed in the immune response between bat species against the same virus. Important differences in percentage of seroconversion against European bat lyssavirus type 1 (EBLV-1) were observed between two species from two distinct families: *Rhinolophus ferrumequinum* (*Rhinolophidae*) and *Myotis myotis* (*Vespertilionidae*). The percentage of seropositive *Rhinolophus ferrumequinum* was much lower than that of *Myotis myotis* [45], suggesting differential rates of seroconversion. Turmelle et al. [52] reported that significant differences in seroconversion rates were found among bats depending on whether they had previously been infected, suggesting that long-term repeated infections of bats might confer significant immunological memory and reduced susceptibility to rabies infection. Immune competence in bats can vary with body condition (via nutritional status and stress) and reproductive activity and, as a consequence, can lead to a lower rabies seroprevalence between or within bat species.
