How Bat Viruses Jump Species
#15,502
Until SARS emerged from China roughly 18 years ago (see SARS and Remembrance), only four coronaviruses (Alpha coronaviruses 229E and NL63, and Beta coronaviruses OC43 & HKU1) were known to infect humans.
Human coronaviruses generally produce mild upper respiratory illnesses and are probably responsible for 15%-30% of the `common colds’ around the world, Only rarely do they migrate to the lower respiratory tract (cite).
In 2012 the MERS-CoV virus emerged from camels in the Middle East, causing severe, often fatal respiratory illness in humans. Like SARS before it, MERS viruses initially spread via intermediary hosts, and are believed to be of bat-origin.
SARS-CoV-2, which emerged in late 2019 as a pandemic virus, is also assumed to have jumped from bats - either directly, or via an intermediate host - to humans.
There are many other coronaviruses that infect other non-human species - including bats, horses, cattle, and swine - raising concerns that other coronaviruses might be capable of jumping to humans as well.
In 2014, in SECD: Another Emerging Coronavirus Threat - in the wake of several newly discovered coronaviruses detected in North American swine - we looked at growing concerns that some porcine-adapted coronaviruses might have zoonotic potential, given the similar physiology between our two species.
Fast forward to the summer of 2017, and in the EID Journal: A New Bat-HKU2–like Coronavirus in Swine, China, 2017, we looked at the recent discovery of a new HKU2-like coronavirus in Chinese pigs showing symptoms of PED (Porcine Epidemic Diarrhea), which they tentatively named porcine enteric alphacoronavirus (PEAV).
HKU2 being one of a number of coronaviruses discovered in the wild (in this case, in Horseshoe bats) by Hong Kong researchers in the years immediately following the SARS epidemic.
All of which brings us to a new study in PNAS that finds this new HKU2-like virus (now dubbed Swine acute diarrhea syndrome coronavirus (SADS-CoV)) virus replicates efficiently in a variety of human cells, making it potentially a zoonotic threat.
First a link, and a brief excerpt from the research article, followed by a press release from UNC-Chapel Hill University where the research was conducted. Follow the link to read the study in its entirety.
Caitlin E. Edwards, Boyd L. Yount, Rachel L. Graham, Sarah R. Leist,Yixuan J. Hou, Kenneth H. Dinnon III, Amy C. Sims, Jesica Swanstrom, Kendra Gully, VTrevor D. Scobey, Michelle R. Cooley, Caroline G. Currie, Scott H. Randell, and Ralph S. BaricPNAS first published October 12, 2020; https://doi.org/10.1073/pnas.2001046117
AbstractZoonotic coronaviruses represent an ongoing threat, yet the myriads of circulating animal viruses complicate the identification of higher-risk isolates that threaten human health. Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a newly discovered, highly pathogenic virus that likely evolved from closely related HKU2 bat coronaviruses, circulating in Rhinolophus spp. bats in China and elsewhere.
As coronaviruses cause severe economic losses in the pork industry and swine are key intermediate hosts of human disease outbreaks, we synthetically resurrected a recombinant virus (rSADS-CoV) as well as a derivative encoding tomato red fluorescent protein (tRFP) in place of ORF3. rSADS-CoV replicated efficiently in a variety of continuous animal and primate cell lines, including human liver and rectal carcinoma cell lines.
Of concern, rSADS-CoV also replicated efficiently in several different primary human lung cell types, as well as primary human intestinal cells. rSADS-CoV did not use human coronavirus ACE-2, DPP4, or CD13 receptors for docking and entry. Contemporary human donor sera neutralized the group I human coronavirus NL63, but not rSADS-CoV, suggesting limited human group I coronavirus cross protective herd immunity.
Importantly, remdesivir, a broad-spectrum nucleoside analog that is effective against other group 1 and 2 coronaviruses, efficiently blocked rSADS-CoV replication in vitro. rSADS-CoV demonstrated little, if any, replicative capacity in either immune-competent or immunodeficient mice, indicating a critical need for improved animal models.
Efficient growth in primary human lung and intestinal cells implicate SADS-CoV as a potential higher-risk emerging coronavirus pathogen that could negatively impact the global economy and human health.
Swine coronavirus replicates in human cells
UNC-Chapel Hill scientists reveal potential of swine coronavirus jumping from animals to people
UNIVERSITY OF NORTH CAROLINA AT CHAPEL HILL
New research from the University of North Carolina at Chapel Hill suggests that a strain of coronavirus that has recently alarmed the swine industry may have the potential to spread to humans as well.
The coronavirus strain, known as swine acute diarrhea syndrome coronavirus (SADS-CoV), emerged from bats and has infected swine herds throughout China since it was first discovered in 2016. Outbreaks of such an illness have the potential to wreak economic havoc in many countries across the globe that rely on the pork industry.
The virus' potential threat to people was demonstrated in lab tests that revealed SADS-CoV efficiently replicated in human liver and gut cells, as well as airway cells. The findings were published Oct. 12 in PNAS.
Though it is in the same family of viruses as the betacoronavirus SARS-CoV-2, which causes the respiratory illness COVID-19 in humans, SADS-CoV is an alphacoronavirus that causes gastrointestinal illness in swine. The virus causes severe diarrhea and vomiting and has been especially deadly to young piglets.
SADS-COV is also distinct from two circulating common cold alphacoronaviruses in humans, HCoV-229E and HCoV-NL63.
"While many investigators focus on the emergent potential of the betacoronaviruses like SARS and MERS, actually the alphacoronaviruses may prove equally prominent -- if not greater -- concerns to human health, given their potential to rapidly jump between species," said Ralph Baric, professor of epidemiology at UNC-Chapel Hill Gillings School of Global Public Health.
While SADS-CoV has not been known to affect humans to-date, the COVID-19 pandemic serves as a potent reminder that many coronavirus strains found in animals have the potential to infect humans as well - an effect known as spillover.
The Baric lab worked with Caitlin Edwards, a research specialist and master of public health student at UNC-Chapel Hill, on the study which suggests humans may be susceptible to spillover of SADS-CoV.
Edwards, the study's first author, tested several types of cells by infecting them with a synthetic form of SADS-CoV to understand just how high the risk of cross-species contamination could be.
Evidence from the study indicates that a wide range of mammalian cells, including primary human lung and intestinal cells, are susceptible to infection. According to Edwards, SADS-CoV shows a higher rate of growth in intestinal cells found in the human gut, unlike SARS-CoV-2, which primarily infects lung cells.
Cross-protective herd immunity often prevents humans from contracting many coronaviruses found in animals. However, results from the testing done by Edwards and her team suggest that humans have not yet developed such immunity to SADS-CoV.
"SADS-CoV is derived from bat coronaviruses called HKU2, which is a heterogenous group of viruses with a worldwide distribution," Edwards said. "It is impossible to predict if this virus, or a closely related HKU2 bat strain, could emerge and infect human populations. However, the broad host range of SADS-CoV, coupled with an ability to replicate in primary human lung and enteric cells, demonstrates potential risk for future emergence events in human and animal populations."
In response to these findings, Edwards and colleagues tested the broad-spectrum antiviral remdesivir as a potential method of treatment for the infection.
Working with Gilead Sciences, remdesivir was developed by the Baric Lab to combat all known coronaviruses, including SADS-CoV. It is currently being used to treat COVID-19 infections in humans, including the United States president. Preliminary results from this study show that it has robust activity against SADS-CoV, though Edwards cautions that more testing is necessary on additional cell types and in animals to confirm these findings.
"Promising data with remdesivir provides a potential treatment option in the case of a human spillover event," she said. "We recommend that both swine workers and the swine population be continually monitored for indications of SADS-CoV infections to prevent outbreaks and massive economic losses."
SADS-CoV could also pose a threat to the U.S. economy, which was third in global pork production in 2019. In 2012, the U.S. pork industry was devastated by different swine coronavirus that emerged from China.
"Not surprisingly, we are currently looking for partners to investigate the potential of SADS-CoV vaccine candidates to protect swine," Baric said. "While surveillance and early separation of infected piglets from sows provide an opportunity to mitigate larger outbreaks and the potential for spillover into humans, vaccines may be key for limiting global spread and human emergence events in the future."
It is worth noting that last year's day-long pandemic tabletop scenario created by the Johns Hopkins Center For Health Security (see The JHCHS #Event201 (Fictional) CAPS Pandemic Scenario) envisioned a novel coronavirus having jumped from pigs to humans in Brazil.
While novel influenza viruses have long been viewed as posing the greatest pandemic threat - coronaviruses over the past two decades have gained a lot of street cred - and given the events of the past 10 months, have to be considered a genuine, and ongoing threat.
For some past blogs on porcine coronaviruses, you may wish to revisit:
