Bat-associated Viruses

Zoonotic pathogens

Viruses that ‘spillover’ from bats to humans and other vertebrates are an example of ‘zoonotic’ pathogens. Zoonoses (singular – ‘zoonosis’) are infectious agents such as viruses, bacteria, and fungi that can be naturally transmitted between humans and other vertebrates, including wild and domestic animals.

On the rise

The number of emerging zoonoses and the geographic distribution of previously known zoonotic pathogens have increased in recent decades (Daszak et al., 2000; Jones et al., 2008). More than half of all infectious diseases that affect human populations (60%) result from pathogens that are shared with animals, both wild and domestic, and 75% of emerging zoonotic diseases are attributed to pathogens with origins in wildlife reservoirs (Jones et al., 2008; Woolhouse and Gowtage-Sequeria, 2005). Rapid modification of the environment and human encroachment promotes interactions between humans, domestic animals, and wildlife species, facilitating disease spillover and presenting a challenge to global health and food security in addition to wildlife conservation (Karesh et al., 2012). These shared drivers of disease emergence and biodiversity loss are increasingly recognized as warranting a coordinated approach to monitor, detect, and mitigate changes in ecological conditions that may result in increased disease risk (WHO-CBD, 2015).

Bats as viral reservoirs

Bat-associated viruses have contributed to thousands of human deaths and economic losses exceeding billions of dollars (Karesh et al., 2012; Hayman, 2016), notably Nipah and Hendra paramyxoviruses, severe acute respiratory syndrome (SARS) and SARS-like coronaviruses, swine acute diarrhea syndrome coronavirus (SADS-CoV), and Ebola and Marburg filoviruses (Olival and Hayman, 2014; Hayman, 2016; Han et al., 2015; Field, 2009; Zhou et al., 2018). While almost all mammalian orders have species that host viruses capable of infecting humans, after controlling for bias in research effort, bats (Order Chiroptera) host a significantly higher proportion of zoonoses per species compared to other orders (Olival et al., 2017). Whether or not bats are “special” (i.e., are there order-specific traits that make bats especially tolerant or resistant to viral infection?) is an active area of ongoing research (Olival et al., 2015; Schountz et al., 2017). While bats are unique morphologically as the only true flying mammals, it is likely that a combination of other physiological, immunological, and life history factors, some of them directly related to flight, may make them important as viral reservoirs. These may include synchronous birthing cycles, exceedingly large population aggregations formed by gregarious species, use of torpor and hibernation in some temperate bat species, daily body temperature spikes associated with flight (i.e., the “flight fever hypothesis”), and unique aspects of immune function (Olival et al., 2015; Calisher et al., 2006; Hayman, 2016; Wang and Cowled, 2015; O’Shea et al., 2014; Zhang et al., 2013).

Bat-associated Coronaviruses (CoVs)

Bats are known to harbor diverse assemblages of viruses in at least 24 viral families (Hayman, 2016). One viral family of particular concern are coronaviruses (CoVs), especially given the public health importance and pandemic potential of SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Bats are likely the evolutionary origin hosts of α- and β-CoVs, including the presumptive progenitor hosts of several CoVs with human and agricultural significance, notably Human CoV-NL63, Human CoV-229E, porcine epidemic diarrhea virus (PEDV), SARS-CoV, MERS-CoV, and SADS-CoV (Woo et al., 2009; Hu et al., 2015). Bats harbor a considerable diversity of CoVs, and are the most likely evolutionary source of MERS-CoV, although the virus is currently circulating in dromedary camels and is transmitted to people via camels in the Middle East and North and East Africa (Memish et al., 2013; Anthony et al., 2017; Ithete et al., 2013; Al-Omari et al., 2019). There is strong evidence demonstrating that SARS-CoV is a virus with evolutionary origins in bats that first emerged in the wet markets of southern China in 2002 (Ge et al., 2013; Li et al., 2005), but also continues to pose a risk in the region with evidence for ongoing spillover to humans (Wang et al., 2018).

Despite their importance to public health and food security and their overall propensity to spread among host species (Hu et al., 2015), there have been few in-depth ecological studies on host-CoVs dynamics. Additional CoV discovery and characterization from undersampled regions of the world (Anthony et al., 2017), as well as longitudinal sampling, field investigations, and in-depth environmental characterization, are needed to further understand the risk of future CoV emergence.

Research on bat-associated viruses

As with publications on bats, research effort on bat-associated viruses is heavily skewed towards the United States, a country with a nationwide surveillance program for monitoring and reporting of rabies virus infections since 1938 (Wallace et al., 2014), followed by Australia, China, northern and central Europe, Japan, and Brazil.

Research gap in Western Asia

While Western Asia contains “hotspot” areas predicted to be high risk for emerging infectious zoonotic diseases (Allen et al., 2017), there have been very few publications on bat-associated viruses in Western Asia (Phelps et al., 2019). Of the 20 countries comprising Western Asia, only two have more publications on bat-associated viruses than the global average of 20 publications/country, specifically Jordan and Saudi Arabia (21 and 29 publications indexed on PubMed, respectively). However, the amount of true bat-associated virus research occurring in the region is likely overestimated. Many publications on bat-associated viruses in Western Asia are review papers or experimental laboratory studies that reference bats as an origin host or follow up studies from MERS-CoV investigations in other hosts (i.e., dromedary camels). The number of surveillance or discovery studies on bat-associated viruses in Western Asia is scant, with a study on hantaviruses in bats from Georgia (Gu et al., 2014) being one of the few non-CoV publications from the region.

Recent outbreaks of CoVs in humans and domestic animals elevates the viral family Coronaviridae to be of great concern as a likely source of new emerging infectious diseases, and a priority for future viral surveillance efforts. Based on our current understanding of CoV systematics, all human CoVs have evolutionary origins in wildlife reservoirs, with SARS-CoV, MERS-CoV, and human-CoVs NL63 and 229E considered to have originated in bats (Hu et al., 2015; Cui et al., 2018; Banerjee et al., 2019). Moreover, spillover of bat-associated CoVs has occurred into domestic animals, for example, SADS-CoV has a 90% mortality rate in young piglets (Cui et al., 2018). On a global scale, reported CoV diversity mirrored species richness, suggesting regions with greater species richness will also have higher CoV diversity.

Viruses affecting bat health

While bats are often assumed to harbor viruses with little to no evidence of symptoms, some bat viruses can cause morbidity or mortality in bats. For example, some bat species can succumb to lyssavirus infections (e.g., rabies virus, European bat 1 lyssavirus, and Lagos bat virus) even though they have a long history of viral–host co-evolution, and bats are important in maintaining lyssavirus diversity in nature (Wallace et al., 2014; Banyard et al., 2014; Banyard et al., 2011). Also, a recently discovered filovirus, Lloviu virus, found in Miniopterus schreibersii, a bat species widely distributed across Europe and Asia, appears to have contributed to multiple bat die-offs in France, Spain, and Portugal in 2002, and at least two mass mortality events in Hungary since 2013 (Kemenesi et al., 2018; Negredo et al., 2011). While the zoonotic potential of the Lloviu virus has not been characterized, this highlights that some bat-associated viruses may also be pathogenic to bats and are a conservation threat to bat populations.