The unusual cases of pneumonia began to appear in midwinter, in China. The cause, researchers would later learn, was a coronavirus new to science. By March, the infection began to spread to other Asian countries and overseas. People were dying, and the World Health Organization issued a global health alert
But this was 2003, not 2020, and the disease was SARS, not Covid-19. By June, the outbreak was almost gone, with just 8,098 confirmed infections and 774 deaths worldwide. No cases of SARS have been reported since 2004

Fielding, Burtram C

University of the Western Cape Research Repository

10/20/2020 How viruses evolvehttps://knowablemagazine.org/article/health-disease/2020/how-viruses-evolve 1/12THow viruses evolvePathogens that switch to a new host species have some adapting to do. How does that a ectthe course of a pandemic like Covid-19? 07.16.2020Help us make scienti c knowledge accessible to all Support free, nonpro t, fact-based journalism Donate todayhe unusual cases of pneumonia began to appear in midwinter, in China. The cause, researcherswould later learn, was a coronavirus new to science. By March, the infection began to spread toother Asian countries and overseas. People were dying, and the World Health Organization issued aglobal health alert.Explore Knowable’s coronavirus coverageBut this was 2003, not 2020, and the disease was SARS, not Covid-19. By June, the outbreak was almostgone, with just 8,098 con rmed infections and 774 deaths worldwide. No cases of SARS have beenreported since 2004.HEALTH &  DISEASEBy Bob Holmes10/20/2020 How viruses evolvehttps://knowablemagazine.org/article/health-disease/2020/how-viruses-evolve 2/12Contrast that with the closely related coronavirus that causes Covid-19 today: more than 13,600,000con rmed cases as of July 16, and more than 585,000 deaths.Why did SARS go away while today’s coronavirus just keeps on spreading? Why, for that ma er, didboth these coronaviruses spill over into people at all, from their original bat hosts?And just as vital as those questions is another: What happens next?YOU MAY ALSO LIKEHEALTH & DISEASEMini-organs push along Covid-19 and other virus researchHEALTH & DISEASEThe time of trials: Waiting for a coronavirus vaccineAs we face the current pandemic, it will be important to understand how SARS-CoV-2, the virus thatcauses Covid-19, is likely to evolve in the months and years ahead. It’s possible the virus could lose itslethal character and se le into an evolutionary détente with humanity. It might end up as just anothercold virus, as may have happened to another coronavirus in the past. But it could also remain a seriousthreat or perhaps even evolve to become more lethal. The outcome depends on the complex andsometimes subtle interplay of ecological and evolutionary forces that shape how viruses and theirhosts respond to one another.“One thing you learn about evolution is never to generalize,” says Edward Holmes, an evolutionaryvirologist at the University of Sydney, Australia, and author of an article on the evolution of emergingviruses in the Annual Review of Ecology, Evolution, and Systematics. “It depends entirely on thebiological nuance of the situation.”Steps to viral successMany of the scariest viruses that have caused past or current epidemics originated in other animals andthen jumped to people: HIV from other primates, in uenza from birds and pigs, and Ebola probablyfrom bats. So, too, for coronaviruses: The ones behind SARS (severe acute respiratory syndrome), MERS(Middle East respiratory syndrome) and Covid-19 all probably originated in bats and arrived in peoplevia another, stepping-stone species, likely palm civets, camels and possibly pangolins, respectively.10/20/2020 How viruses evolvehttps://knowablemagazine.org/article/health-disease/2020/how-viruses-evolve 3/12But making the jump from one species to another isn’t easy, because successful viruses have to betightly adapted to their hosts. To get into a host cell, a molecule on the virus’s surface has to match areceptor on the outside of the cell, like a key   ing into a lock. Once inside the cell, the virus has toevade the cell’s immune defenses and then commandeer the appropriate parts of the host’sbiochemistry to churn out new viruses. Any or all of these factors are likely to di er from one hostspecies to another, so viruses will need to change genetically — that is, evolve — in order to set up shopin a new animal.Pandemics — disease outbreaks of global reach — have visitedhumanity many times. Here are examples.Host switching actually involves two steps, though these can overlap. First, the virus has to be able toinvade the new host’s cells: That’s a minimum requirement for making the host sick. But to becomecapable of causing epidemics, the virus also has to become infectious — that is, transmissible betweenindividuals — in its new host. That’s what elevates a virus from an occasional nuisance to one capable ofcausing widespread harm.SARS-CoV-2 shows these two stages clearly. Compared with the virus in bats, both the virus that infectspeople and a close relative in pangolins carry a mutation that changes the shape of the surface “ spikeprotein.” The alteration is right at the spot that binds to host cell receptors to let the virus in. This10/20/2020 How viruses evolvehttps://knowablemagazine.org/article/health-disease/2020/how-viruses-evolve 4/12suggests that the mutation  rst arose either in pangolins or an as yet unidenti ed species andhappened to allow the virus to jump over to people, too.But SARS-CoV-2 carries other changes in the spike protein that appear to have arisen after it jumped topeople, since they don’t occur in the bat or pangolin viruses. One is in a region called the polybasiccleavage site, which is known to make other coronaviruses and  u viruses more infectious. Anotherappears to make the spike protein less fragile, and in lab experiments with cell cultures, it makes thevirus more infectious. The mutation has become more common as the Covid-19 pandemic goes on,which suggests — but does not prove — that it makes the virus more infectious in the real world, too.(Fortunately, though it may increase spread, it doesn’t seem to make people sicker.)10/20/2020 How viruses evolvehttps://knowablemagazine.org/article/health-disease/2020/how-viruses-evolve 5/12A recent mutation alters the SARS-CoV-2 spike protein to make it less fragile (the altered bits are shown as colored blobs). This addedrobustness appears to make the virus more infectious. Three sites are shown because the spike protein is composed of threeidentical subunits that bind together.This evolutionary two-step —  rst spillover, then adaptation to the new host — is probablycharacteristic of most viruses as they shift hosts, says Daniel Streicker, a viral ecologist at the Universityof Glasgow. If so, emerging viruses probably pass through a “silent period” immediately after a hostshift, in which the virus barely scrapes by, teetering on the brink of extinction until it acquires themutations needed for an epidemic to bloom.10/20/2020 How viruses evolvehttps://knowablemagazine.org/article/health-disease/2020/how-viruses-evolve 6/12Streicker sees this in studies of rabies in bats — which is a good model for studying the evolution ofemerging viruses, he says, since the rabies virus has jumped between di erent bat species many times.He and his colleagues looked at decades’ worth of genetic sequence data for rabies viruses that hadundergone such host shifts. Since larger populations contain more genetic variants than smallerpopulations do, measuring genetic diversity in their samples enabled the scientists to estimate howwidespread the virus was at any given time.The team found that almost none of the 13 viral strains they studied took o  immediately afterswitching to a new bat species. Instead, the viruses eked out a marginal existence for years to decadesbefore they acquired the mutations — of as yet unknown function — that allowed them to burst out toepidemic levels. Not surprisingly, the viruses that emerged the fastest were those that needed thefewest genetic changes to blossom.SARS-CoV-2 probably passed through a similar tenuous phase before it acquired the key adaptationsthat allowed it to  ourish, perhaps the mutation to the polybasic cleavage site, perhaps others not yetidenti ed. In any case, says Colin Parrish, a virologist at Cornell University who studies host shifts, “bythe time the  rst person in Wuhan had been identi ed with coronavirus, it had probably been inpeople for a while.”It was our bad luck that SARS-CoV-2 adapted successfully. Many viruses that spill over to humans neverdo. About 220 to 250 viruses are known to infect people, but only about half are transmissible — manyonly weakly — from one person to another, says Jemma Geoghegan, an evolutionary virologist at theUniversity of Otago, New Zealand. The rest are dead-end infections. Half is a generous estimate, sheadds, since many other spillover events probably  zzle out before they can even be counted.10/20/2020 How viruses evolvehttps://knowablemagazine.org/article/health-disease/2020/how-viruses-evolve 7/12Funeral for a US soldier who died of in uenza in Russia in 1919. The 1918-1920 pandemic killed an estimated 50 million peopleworldwide.CREDIT: US NATIONAL ARCHIVESGetting nicer — or nastierSARS-CoV-2, of course, is well past the teetering stage. The big question now is: What happens next?One popular theory, endorsed by some experts, is that viruses often start o  harming their hosts, butevolve toward a more benign coexistence.  After all, many of the viruses we know of that trigger severeproblems in a new host species cause mild or no disease in the host they originally came from. Andfrom the virus’s perspective, this theory asserts, hosts that are less sick are more likely to be movingaround, meeting others and spreading the infection onward.  “I believe that viruses tend to become less pathogenic,” says Burtram Fielding, a coronavirologist at theUniversity of the Western Cape, South Africa. “The ultimate aim of a pathogen is to reproduce, to makemore of itself. Any pathogen that kills the host too fast will not give itself enough time to reproduce.” If10/20/2020 How viruses evolvehttps://knowablemagazine.org/article/health-disease/2020/how-viruses-evolve 8/12SARS-CoV-2 can spread faster and further by killing or severely harming fewer of the people it infects,we might expect that over time, it will become less harmful — or, as virologists term it, less virulent.This kind of evolutionary gentling may be exactly what happened more than a century ago to one ofthe other human coronaviruses, known as OC43, Fielding suggests. Today, OC43 is one of fourcoronaviruses that account for up to a third of cases of the common cold (and perhaps occasionallymore severe illness). But Fielding and a few others think it could also have been the virus behind aworldwide pandemic, usually ascribed to in uenza, that began in 1890 and killed more than a millionpeople worldwide, including Queen Victoria’s grandson and heir.“Everyone has in uenza,” says the headline in a French publication from January, 1890.CREDIT: WELLCOME COLLECTIONScientists can’t prove that, because no virus samples survive from that pandemic, but somecircumstantial evidence makes the case plausible, Fielding says. For one thing, people who were10/20/2020 How viruses evolvehttps://knowablemagazine.org/article/health-disease/2020/how-viruses-evolve 9/12infected in the 1890 pandemic apparently experienced nervous-system symptoms we now see as moretypical of coronaviruses than of in uenza. And when Belgian researchers sequenced OC43’s genome in2005 and compared it to other known coronaviruses, they concluded that it likely originated as a ca levirus and may have jumped to people right around 1890. They speculated that it may have caused the1890 pandemic and then se led down to a less nasty coexistence as an ordinary cold virus. Other evolutionary biologists disagree. The pandemic certainly faded as more people became immune,but there’s no solid evidence that OC43 itself evolved from highly virulent to mostly benign over thelast century, they say. Even if it did, that does not mean SARS-CoV-2 will follow the same trajectory. “Youcan’t just say it’s going to become nicer, that somehow a well-adapted pathogen doesn’t harm its host.Modern evolutionary biology, and a lot of data, shows that doesn’t have to be true. It can get nicer, andit can get nastier,” says Andrew Read, an evolutionary microbiologist at Penn State University. (Holmesis blunter: “Trying to predict virulence evolution is a mug’s game,” he says.)To understand why it’s so hard to predict changes in virulence, Read says it’s important to recognize thedi erence between virulence — that is, how sick a virus makes its host — and its transmissibility, or howeasily it passes from one host individual to another. Evolution always favors increased transmissibility,because viruses that spread more easily are evolutionarily   er — that is, they leave more descendants.But transmissibility and virulence aren’t linked in any dependable way, Read says. Some germs do just ne even if they make you very sick. The bacteria that cause cholera spread through diarrhea, so severedisease is good for them. Malaria and yellow fever, which are transmi ed by mosquitos, can spread just ne even from a person at death’s door.Respiratory viruses, like in uenza and the human coronaviruses, need hosts that move around enoughto breathe on one another, so extremely high virulence might be detrimental in some cases. But there’sno obvious evolutionary advantage for SARS-CoV-2 to reduce its virulence, because it pays li le pricefor occasionally killing people: It spreads readily from infected people who are not yet feeling sick, andeven from those who may never show symptoms of illness. “To be honest, the novel coronavirus ispre y  t already,” Geoghegan says.Nor are there many documented instances of viruses whose virulence has abated over time. The rare,classic example is the myxoma virus, which was deliberately introduced to Australia in the 1950s fromSouth America to control invasive European rabbits. Within a few decades, the virus evolved to reduceits virulence, albeit only down to 70 to 95 percent lethality from a whopping 99.8 percent. (It has sinceticked up again.)10/20/2020 How viruses evolvehttps://knowablemagazine.org/article/health-disease/2020/how-viruses-evolve 10/12But myxoma stands nearly alone, Parrish says. For instance, he notes, there is no evidence that recenthuman pathogens such as Ebola, Zika or chikungunya viruses have shown any signs of becoming lesspathogenic in the relatively short time since jumping to humans.After rabbits were introduced to Australia, their population exploded. “They are very plentiful here,” says the handwritten inscriptionon the back of this postcard from around 1930. Scientists eventually introduced the myxoma virus to control the rabbit plague.CREDIT: PHOTOGRAPHER PAUL C. NOMCHONG / NATIONAL MUSEUM OF AUSTRALIAThe ones that went awayThe faded nightmares of our past — pandemics that terrorized, then receded, such as SARS in 2003 and u in 1918-20 and again in 1957, 1968 and 2009 — went away not because the viruses evolved to causemilder disease, but for other reasons. In the case of SARS, the virus made people sick enough thathealth workers were able to contain the disease before it got out of hand. “People who got SARS gotvery sick, very fast and were easily identi ed, easily tracked and readily quarantined — and theircontacts were also readily identi ed and quarantined,” says Mark Cameron, an immunologist at CaseWestern Reserve University in Cleveland, who worked in a Toronto hospital during the height of theSARS outbreak there. That was never going to be as easy to do for Covid-19 because people who don’tshow symptoms can spread the virus.10/20/2020 How viruses evolvehttps://knowablemagazine.org/article/health-disease/2020/how-viruses-evolve 11/12Flu pandemics, meanwhile, have tended to recede for another reason, one that o ers more hope in ourpresent moment: Enough of the population eventually becomes immune to slow the virus down. TheH1N1 in uenza virus that caused the 1918 pandemic continued as the main in uenza virus until the1950s, and its descendants still circulate in the human population. What made the virus such a threatin 1918-20 is that it was novel and people had li le immunity. Once much of the population had beenexposed to the virus and had developed immunity, the pandemic waned, although the virus persistedat a lower level of infections — as it does to this day. It appears less lethal now largely because olderpeople, who are at greatest risk of dying from in uenza, have usually encountered H1N1 in uenza orsomething like it at some point in their lives and retain some degree of immunity, Read says.With the new coronavirus, Parrish says, “we’re sort of in that 1918 period where the virus is spreadingfast in a naive population.” But that will change as more people either catch Covid-19 or are vaccinated(if and when that becomes possible) and develop some level of immunity. “There’s no question thatonce the population is largely immune, the virus will die down,” Parrish says.The question is how long that immunity will last: for a lifetime, like smallpox, or just a few years, like u? In part, that will depend on whether the vaccine induces a permanent antibody response or just atemporary one. But it also depends on whether the virus can change to evade the antibodies generatedby the vaccine. Although coronaviruses don’t accumulate mutations as fast as  u viruses, they do stillchange. And at least one, which causes bronchitis in chickens, has evolved new variants that aren’tcovered by previous vaccines. But at this point, no one knows what to expect from SARS-CoV-2.There is, at least, one encouraging aspect to all this. Even if we can’t predict how the virus will evolve orhow it will respond to the coming vaccine, there is something all of us can do to reduce the risk of thevirus evolving in dangerous ways. And it doesn’t involve any complicated new behaviors. “Viruses canonly evolve if they’re replicating and transmi ing,” Streicker says. “Anything that reduces thereplication of a virus will in consequence reduce the amount of evolution that happens.” In otherwords, we can do our part to slow down the evolution of the Covid-19 virus by behaving exactly as we’vebeen told to already to avoid catching it: Minimize contact with others, wash your hands and wear amask.10.1146/knowable-071520-1Bob Holmes is a science writer in Edmonton, Canada, who hopes not to contribute to the further evolution of SARS-CoV-2.REPUBLISH THIS ARTICLE10/20/2020 How viruses evolvehttps://knowablemagazine.org/article/health-disease/2020/how-viruses-evolve 12/12Knowable Magazine is from Annual Reviews, a nonpro t publisher dedicated to synthesizing andintegrating knowledge for the progress of science and the bene t of society.© 2020 Annual Reviews, Inc       DONATE | ABOUT | STAFF | CONTACT | NEWSLETTER | REPUBLISH |PRIVACY POLICYHealth & Disease Living World Coronavirus Genetics Public HealthSHARE THIS ARTICLE       Support Knowable MagazineYour generosity will help us con nue making scien fic knowledge accessible to all.DONATE

How viruses evolve

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How viruses evolve

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