The bat connection
Basic research into the epidemiology of coronavirus needs to be taken up on a war footing.
WHY ARE BATS (CHIROPTERA) A PREFERRED host for so many zoonotic diseases? Some of their characteristics (food choices, colonial or solitary nature, population structure, ability to fly, seasonal migration and daily movement patterns, torpor and hibernation, life span, roosting behaviours, ability to echolocate, virus susceptibility, and so on) make them exquisitely suitable. Recent observations of outbreaks and epidemics of newly recognised human and livestock diseases caused by viruses transmitted by various megachiropteran and microchiropteran bats have drawn attention anew to these remarkable mammals. According to literature, 66 viruses have been isolated from bats.
Bats are abundant, diverse, and geographically widespread. These mammals provide us with resources, but their importance is minimised and many of their populations and species are at risk, even threatened or endangered. Whereas other mammals, such as rodents and carnivores, may possess traits in common with bats, such as the ability to hibernate, no group of mammals shares the full suite of attributes that make bats unique.
Bats evolved early and have changed relatively little in comparison with mammals of other taxa. Although the fossil record of bat evolution is incomplete, a recent analysis of 17 nuclear genes dated the origin of chiropterans to the Eocene period (52 to 50 million years ago), coincident with a significant rise in global temperature. The correspondingly ancient origins deduced for certain zoonotic viruses maintained in bats suggest a long history of co-speciation. Viruses that evolved with bats may have used for replication cellular receptors and biochemical pathways which are conserved in mammals that evolved later and which underwent radiation in later geological periods and, therefore, these conserved cellular receptors and pathways could enhance the capacity for transmission of bat-associated viruses to other mammals.
We do not know enough about bat biology and we are doing too little in terms of bat conservation. There remain a multitude of questions regarding the role of bats in disease emergence. Of the more than 4,600 recognised species of mammals, 925 (about 20 per cent) are bats. Bats are unique among mammals in their ability to fly. Bats fly daily in pursuit of food, and bats of many species fly long distances during seasonal migrations. For example, bats of the Myotis spp. may travel 200 to 400 miles (one mile is 1.6 kilometres) from their winter hibernation sites. Mexican free-tailed bats (Tadarida brasiliensis mexicana) migrate at least 800 miles between their summer caves in Texas and New Mexico and their overwintering sites in Mexico (they are otherwise very widely distributed).
RABIES AND BATS
In France, rabies virus infections have been associated with the migratory routes of Nathusius’ pipistrelle (Pipistrellus nathusii) bats. Silver-haired bats (Lasionycteris noctivagans) seasonally range from Alaska, across Canada, and south to Texas. Rabies virus variants associated with silver-haired bats and the Eastern Pipistrellus (Pipistrellus subflavus) have been identified from numerous locations throughout the geographic range of these bats and the same variants have been identified as the cause of the majority of cases of indigenously acquired human rabies in the United States and Canada.
Different patterns of migration within the same species of bat, as occurs with relatively solitary species such as the silver-haired bat and colonial cave-dwelling species such as Mexican free-tailed bats may permit exchange of novel viruses or virus variants between migrating and non-migrating subpopulations of bats of other species. A Mexican free-tailed bat infected with a rabies virus variant normally associated with hoary bats (Lasiurus cinereous) suggests interspecies transmission.
In the field, rabid bats of one species have been observed to be aggressive toward bats of other species. Moreover, Shankar et al, in a study of the phylogenies of divergence of rabies viruses from bats and terrestrial animals in Colorado, found that bats of different species had the same genotypic variants, indicating active interspecies transmission of the rabies virus. They concluded that, at least in Colorado, animal rabies occurs principally in bats and that identification of bat-associated variants of rabies viruses in domestic cats, grey foxes (Urocyon cinereoargenteus), and striped skunks (Mephitis mephitis) demonstrates the importance of rabies virus spillover from bats to domestic and terrestrial wild vertebrates. Among Microchiroptera, members from two families, Rhinolophidae and Vespertilionidae, are important because some dangerous viruses (Kyasanur forest disease, or KFD, from Rhinolophus rouxi, Corona from Rhinolophus sinicus and Ebola from Miniopterus inflatus) have been isolated from them.
Ever since the implication of the horseshoe bat, Rhinolophus rouxi, in the epidemiology of Kfd—the virus was isolated from these bats and their tick ectoparasite, called Ornithodoros, by this writer in 1969 [Ind.j.med.res.res, 57(5)]—one would have thought that interest in the role of bats would have been stimulated. A few articles on the role of bats have also been published since (“Tracking arboviruses”, Frontline, August 4, 2017; “Viral challenge”, Frontline, March 1, 2019; J.com.dis, 51(4), 2019). It is really unfortunate that present-day researchers in India are not looking at bats while investigating the recurrence of KFD in January 2019 and the sporadic occurrence of KFD cases in different pockets all along the Western Ghats region. Of course, Ebola has not yet become a problem in India, but it can invade India anytime, just as coronavirus has done now. The Zika virus almost came to India, but we escaped. I think we forgot Zika afterwards, but will rush into action only when it comes back. Are we prepared?
It is pertinent to talk about the coronavirus natural cycle here. Not much is known about the epidemiology. Proactive measures might ensure that the disease does not take a toll as it did in China, Italy, Iran, and Spain. At the time of writing this, India has about 100+ cases and has had only two deaths. We do not know what the scientific community is doing, except making statements about a potential vaccine which would be ready in a couple of years. But what about basic studies on the epidemic itself? Earlier, I had written about the lead given by Ugandan scientists regarding the Zika virus (“Zika control, the Ugandan way”, Frontline, November 25, 2016). That was about four years ago. Now we have another inspiring story from the investigators of the Chinese coronavirus epidemic. Their example is inspir
ing and worth emulating (“How China’s ‘Bat Woman’ Hunted Down Viruses from SARS to the New Coronavirus”, Jane Qiu, Scientific American, March 11, 2020) and I quote below:
INSPIRING EXAMPLE
“Beijing—the mysterious patient samples arrived at Wuhan Institute of Virology at 7 p.m. on December 30, 2019. Moments later, Shi Zhengli’s cell phone rang. It was her boss, the institute’s director. The Wuhan Center for Disease Control and Prevention had detected a novel coronavirus in two hospital patients with atypical pneumonia, and it wanted Shi’s renowned laboratory to investigate. If the finding was confirmed, the new pathogen could pose a serious public health threat—because it belonged to the same family of bat-borne viruses as the one that caused severe acute respiratory syndrome (SARS), a disease that plagued 8,100 people and killed nearly 800 of them between 2002 and 2003. ‘Drop whatever you are doing and deal with it now,’ she recalls the director saying.
“Shi—a virologist who is often called China’s ‘bat woman’ by her colleagues because of her virus-hunting expeditions in bat caves over the past 16 years—walked out of a conference in Shanghai and hopped on the next train back to Wuhan. ‘I wondered if [the municipal health authority] got it wrong,’ she says. ‘I had never expected this kind of thing to happen in Wuhan, in central China.’ Her studies had shown that the southern, subtropical areas of Guangdong, Guangxi and Yunnan have the greatest risk of coronaviruses jumping to humans from animals—particularly bats, a known reservoir for many viruses.…
“While Shi’s team at the Chinese Academy of Sciences institute raced to uncover the identity and origin of the contagion, the mysterious disease spread like wildfire.… The epidemic is one of the worst to afflict the world in recent decades. Scientists had warned that the rate of emergence of new infectious diseases is accelerating— especially in developing countries where high densities of people and animals increasingly mingle and move about ....
“To Shi, her first virus-discovery expedition felt like a vacation. On a breezy, sunny spring day in 2004, she joined an international team of researchers to collect samples from bat colonies in caves near Nanning, the capital of Guangxi. Her inaugural cave was typical of the region: large, rich in limestone columns and—being a popular tourist destination—easily accessible. ‘It was spellbinding,’ Shi recalls, with milky-white stalactites hanging from the ceiling like icicles, glistening with moisture.
“But the holiday like atmosphere soon dissipated. Many bats—including several insect-eating species of horseshoe bats that are abundant in southern Asia— roost in deep, narrow caves on steep terrain. Often guided by tips from local villagers, Shi and her colleagues had to hike for hours to potential sites and inch through tight rock crevasses on their stomach. And the flying mammals can be elusive. In one frustrating week, the team explored more than 30 caves and saw only a dozen bats.
“These expeditions were part of the effort to catch the culprit in the SARS outbreak, the first major epidemic of the 21st century.… Before SARS, the world had little inkling of coronaviruses—named because, seen under a microscope, their spiky surface resembles a crown—says Linfa Wang, who directs the emerging infectious diseases programme at Singapore’s DUKE-NUS Medical School. Coronaviruses were mostly known for causing common colds. ‘The SARS outbreak was a game changer,’ says Wang, whose work on bat-borne coronaviruses got a swift mention in the 2011 Hollywood blockbuster Contagion. It was the first time a deadly coronavirus with pandemic potential emerged. This discovery helped to jump-start a global search for animal viruses that could find their way into humans….
“In those first virus-hunting months in 2004, whenever Shi’s team located a bat cave, it would put a net at the opening before dusk—and then wait for the nocturnal creatures to venture out to feed for the night. Once the bats were trapped, the researchers took blood and saliva samples, as well as fecal swabs, often working into the small hours. After catching up on some sleep, they would return to the cave in the morning to collect urine and fecal pellets.
“But sample after sample turned up no trace of genetic material from coronaviruses. It was a heavy blow. ‘Eight months of hard work seemed to have gone down the drain,’ Shi says. ‘We thought coronaviruses probably did not like Chinese bats.’ The team was about to give up when a research group in a neighbouring lab handed it a diagnostic kit for testing antibodies produced by people with SARS.
“There was no guarantee the test would work for bat antibodies, but Shi gave it a go anyway. ‘What did we have to lose?’ she says. The results exceeded her expectations. Samples from three horseshoe bat species contained antibodies against the SARS virus. ‘It was a turning point for the project,’ Shi says. The researchers learned that the presence of the coronavirus in bats was ephemeral and seasonal—but an antibody reaction could last from weeks to years….
“Shi’s team used the antibody test to narrow down locations and bat species to pursue in the quest for these genomic clues. After roaming mountainous terrain in the majority of China’s dozens of provinces, the researchers turned their attention to one spot: Shitou Cave on the outskirts of Kunming, the capital of Yunnan—where they conducted intense sampling during different seasons throughout five consecutive years….
“The team discovered hundreds of bat-borne coronaviruses with incredible genetic diversity.”
When will we have someone like Shi Zhengli to inspire and enthuse our scientists? They should go and look for the source of the virus in bats in the wilderness of India. This is basic.