by Gertrud U. Rey
Remember the series of flashbacks in the ending of the movie “Contagion,” which reveal where the virus originated and how the pandemic started? As a tree is cut down, a colony of bats flies out of the tree to seek new shelter. While in flight over a nearby farm, one of the bats drops a piece of half-eaten, virus-contaminated banana, which lands in front of a pig. The pig eats the banana and is later sold, butchered, and taken to the city, where it is prepared by a chef in the kitchen of a fancy restaurant. After handling the infected animal, the chef is called away to pose for a photo with a client (“Beth”) played by Gwyneth Paltrow. The chef heads out of the kitchen without washing his hands and greets Beth with a handshake. Beth ends up being Patient Zero.
This scenario is not purely fictional, but it symbolizes a typical framework for spillover of viruses from non-human animals into humans; and it very likely is similar to a sequence of events that led to the COVID-19 pandemic. Every time the barrier between different animal species is breached, there is potential for the emergence of a new pathogen. Bats, which make up 20% of all mammals, are host and reservoir to many infectious agents. Within the context of infectious disease, a reservoir is a species or population of animals in which a virus can replicate without causing much disease, allowing for its continued existence and potential to spill over into humans. Bats are also the only mammals that can fly, a characteristic that expands their range of movement as they look for food, and one that increases the frequency of bat interactions with members of different animal species. It is therefore in our best interest to monitor the presence of viruses in wild bats and determine their potential for spillover into humans.
To do just that, the authors of a recent article collected rectal swabs from 149 individual bats of fifteen different species located in six counties in the Yunnan province of China. Sequencing of the total RNA isolated from the samples revealed the presence of 55 different viruses, with 42 of these viruses being new and previously uncharacterized. The most prevalent viral species were members of the Reoviridae, Picornaviridae, and Coronaviridae families. Almost half the bats were infected with two or more different viruses, a condition that favors the recombination and reassortment of viral genomes to produce new viruses that may be adapted to infect humans. Furthermore, bats that were closely related to each other shared more of the same viruses than bats that were more distantly related, an observation that confirms our understanding that viruses are specific to certain host organisms.
The authors characterized three coronaviruses and two reoviruses that were closely related to known human or livestock pathogens as “viruses of concern,” meaning that they are at high risk of spilling over into humans. Four of these five viruses were present in more than one bat species. One of the three coronaviruses had particularly high sequence identity to both SARS-CoV and SARS-CoV-2, and it was thus named “SARS-like virus CX1” (referred to as “CX1” in this post). Using functional in vitro assays, the authors determined that CX1 can bind human ACE2, the receptor that mediates host cell entry of both SARS-CoV and SARS-CoV-2. However, unlike SARS-CoV-2 and several seasonal human coronaviruses, the CX1 spike protein does not appear have a furin cleavage site, a domain that increases the potential for transmission because it is recognized and cut by the cellular enzyme furin during exit of new viruses from the cell. These observations suggest that CX1 may be able to infect human cells using the ACE2 receptor, but it may not transmit very well to the next cell and/or individual. It would be useful to carry out additional experiments to analyze the efficiency of CX1 transmission.
The publication of this study coincides with the termination of a US-funded virus hunting program called DEEP VZN (Discovery & Exploration of Emerging Pathogens – Viral Zoonoses), which focused on discovering and cataloging pathogens from around the world. The motivation for ending the program is the fear that a possible mishap may lead to an accidental outbreak or pandemic. This reasoning erroneously implies that if humans do not actively search for viruses in the wild, those viruses cannot harm them. However, spillovers are most likely to happen during human/wildlife interactions that don’t involve safeguards – for example when inhaling aerosolized bat urine or excrement during the exploration of a cave, or while breeding exotic animals in captivity for later sale at wet markets. In contrast, there is no evidence to support the emergence of a novel pathogen following the sampling of wildlife by rigorously trained scientists. Wildlife biologists operate under highly regulated conditions – they wear personal protective equipment, follow meticulously designed protocols, and only collect and transport samples after obtaining the necessary permits. The comparative risk for spillover under these controlled circumstances is very small.
The study described in this post confirms that bats harbor viruses that present an increased risk of emergence in humans, and it re-emphasizes the need for continued surveillance to allow us to predict and prepare for potential pandemic threats.