Mutation Allows Coronavirus to Infect More Cells, Study Finds. Scientists Urge Caution.

By | June 13, 2020

For months, scientists have debated why one genetic variation of the coronavirus became dominant in many parts of the world.

Many scientists argue that the variation spread widely by chance, multiplying outward from explosive outbreaks in Europe. Others have proposed the possibility that a mutation gave it some kind of biological edge and have been urgently investigating the effect of that mutation.

Now, scientists have shown — at least in the tightly controlled environment of a laboratory cell culture — that viruses carrying that particular mutation infect more cells and are more resilient than those without it.

Geneticists cautioned against drawing conclusions about whether the variant, which has been circulating widely since February, spreads more easily in humans. There is no evidence that it is more deadly or harmful, and differences seen in a cell culture do not necessarily mean it is more contagious, they said.

But the new study, which has not yet been peer reviewed, does show that this mutation appears to change the biological function of the virus, experts said. The insight could be a crucial first step in understanding how the mutation behaves at a biomolecular level.

Researchers at Scripps Research, Florida, found that the mutation, known as D614G, stabilized the virus’s spike proteins, which protrude from the viral surface and give the coronavirus its name. The number of functional and intact spikes on each viral particle was about five times higher because of this mutation, they found.

These spike proteins must attach to a cell for a virus to infect it. As a result, the viruses with D614G were far more likely to infect a cell than viruses without that mutation, according to the scientists who led the study, Hyeryun Choe and Michael Farzan.

The D614G Mutation

A tiny mutation in the coronavirus genome may stabilize the spike proteins that protrude from the virus and allow it to infect more cells — at least in laboratory experiments.

The SARS-CoV-2

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&◀ Spike protein

D614G

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&◀ Areas affected by the mutation

ORF1a protein

ORF1b

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The 614th amino acid in the spike protein mutated from D to

G

Spike

protein

D614G

mutation

&◀ Affected area

ORF1a protein

ORF1b

Spike

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M

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The 614th amino acid in the

spike protein mutated from D to

G

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D614G

mutation

Affected

area

ORF1a protein

ORF1b

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The 614th amino acid in the

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By Jonathan Corum | Source: Lizhou Zhang et al., Scripps Research

“Viruses with more functional spikes on the surface would be more infectious,” Dr. Farzan said. “And there are very clear differences between the two viruses in the experiment.” He added: “Those differences just popped out.”

Dr. Choe, the senior author on the paper, said that the virus spikes with the mutation were “nearly 10 times more infectious in the cell culture system that we used” than those without that same mutation.

Mutations are tiny, random changes to viral genetic material that occur as it is copied. The vast majority do not affect the virus’s function, one way or another.

Virologists shown the study said that the Scripps research was a strong demonstration that this specific mutation does indeed cause a significant change in how the virus behaves, biologically.

“This is a powerful experimental study and the best evidence yet that the D614G mutation increases the infectivity of SARS-CoV-2,” said Eddie Holmes, a professor at the University of Sydney and a specialist in viral evolution.

The mutation the researchers studied has predominated in Europe and in much of the United States, especially in the Northeast. They compared it to viruses without that mutation, like those found at the beginning of the pandemic in Wuhan, China.

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Dr. Choe said that the results do suggest that biological factors played a role in the rapid spread of the D614G virus.

“This mutation may explain the predominance of viruses carrying it,” Dr. Choe said.

But other scientists cautioned that it would take significantly more research to determine if differences in the virus were a factor in shaping the course of the outbreak. Other factors clearly played a role in the spread, including the timing of lockdowns, travel patterns and luck, scientists argue.

And luck alone may still be the best explanation for why viruses with the mutation have become so widespread, they said.

Kristian Andersen, a geneticist at Scripps Research, La Jolla, said that analyses of D614G and other variants in Washington and California had so far found no difference in how quickly or widely one variant spread over another.

“That’s the main reason that I’m so hesitant at the moment,” Dr. Andersen said. “Because if one really was able to spread significantly better than the other, then we would expect to see a difference here, and we don’t.”

Tests of the Ebola virus, which spread in West Africa starting in 2013, indicated that a common mutation infected more cells in cell cultures than its competitors, potentially suggesting that the mutated virus was more contagious. But the difference did not hold up when later tested in animals.

Scientists’ attention had begun to focus on the D614G mutation by May, when Bette Korber, a researcher at Los Alamos National Laboratory, posted a paper arguing that “when introduced to new regions it rapidly becomes the dominant form.”

Many scientists criticized the study, saying that its analysis was not sufficient to conclude that the virus with that mutation was more transmissible in humans. The analysis did not adequately account for the role of luck, they said: When a mutation seeds a new outbreak, it can build an advantage by pure chance.

  • Frequently Asked Questions and Advice

    Updated June 12, 2020

    • What’s the risk of catching coronavirus from a surface?

      Touching contaminated objects and then infecting ourselves with the germs is not typically how the virus spreads. But it can happen. A number of studies of flu, rhinovirus, coronavirus and other microbes have shown that respiratory illnesses, including the new coronavirus, can spread by touching contaminated surfaces, particularly in places like day care centers, offices and hospitals. But a long chain of events has to happen for the disease to spread that way. The best way to protect yourself from coronavirus — whether it’s surface transmission or close human contact — is still social distancing, washing your hands, not touching your face and wearing masks.

    • Does asymptomatic transmission of Covid-19 happen?

      So far, the evidence seems to show it does. A widely cited paper published in April suggests that people are most infectious about two days before the onset of coronavirus symptoms and estimated that 44 percent of new infections were a result of transmission from people who were not yet showing symptoms. Recently, a top expert at the World Health Organization stated that transmission of the coronavirus by people who did not have symptoms was “very rare,” but she later walked back that statement.

    • How does blood type influence coronavirus?

      A study by European scientists is the first to document a strong statistical link between genetic variations and Covid-19, the illness caused by the coronavirus. Having Type A blood was linked to a 50 percent increase in the likelihood that a patient would need to get oxygen or to go on a ventilator, according to the new study.

    • How many people have lost their jobs due to coronavirus in the U.S.?

      The unemployment rate fell to 13.3 percent in May, the Labor Department said on June 5, an unexpected improvement in the nation’s job market as hiring rebounded faster than economists expected. Economists had forecast the unemployment rate to increase to as much as 20 percent, after it hit 14.7 percent in April, which was the highest since the government began keeping official statistics after World War II. But the unemployment rate dipped instead, with employers adding 2.5 million jobs, after more than 20 million jobs were lost in April.

    • Will protests set off a second viral wave of coronavirus?

      Mass protests against police brutality that have brought thousands of people onto the streets in cities across America are raising the specter of new coronavirus outbreaks, prompting political leaders, physicians and public health experts to warn that the crowds could cause a surge in cases. While many political leaders affirmed the right of protesters to express themselves, they urged the demonstrators to wear face masks and maintain social distancing, both to protect themselves and to prevent further community spread of the virus. Some infectious disease experts were reassured by the fact that the protests were held outdoors, saying the open air settings could mitigate the risk of transmission.

    • How do we start exercising again without hurting ourselves after months of lockdown?

      Exercise researchers and physicians have some blunt advice for those of us aiming to return to regular exercise now: Start slowly and then rev up your workouts, also slowly. American adults tended to be about 12 percent less active after the stay-at-home mandates began in March than they were in January. But there are steps you can take to ease your way back into regular exercise safely. First, “start at no more than 50 percent of the exercise you were doing before Covid,” says Dr. Monica Rho, the chief of musculoskeletal medicine at the Shirley Ryan AbilityLab in Chicago. Thread in some preparatory squats, too, she advises. “When you haven’t been exercising, you lose muscle mass.” Expect some muscle twinges after these preliminary, post-lockdown sessions, especially a day or two later. But sudden or increasing pain during exercise is a clarion call to stop and return home.

    • My state is reopening. Is it safe to go out?

      States are reopening bit by bit. This means that more public spaces are available for use and more and more businesses are being allowed to open again. The federal government is largely leaving the decision up to states, and some state leaders are leaving the decision up to local authorities. Even if you aren’t being told to stay at home, it’s still a good idea to limit trips outside and your interaction with other people.

    • What are the symptoms of coronavirus?

      Common symptoms include fever, a dry cough, fatigue and difficulty breathing or shortness of breath. Some of these symptoms overlap with those of the flu, making detection difficult, but runny noses and stuffy sinuses are less common. The C.D.C. has also added chills, muscle pain, sore throat, headache and a new loss of the sense of taste or smell as symptoms to look out for. Most people fall ill five to seven days after exposure, but symptoms may appear in as few as two days or as many as 14 days.

    • How can I protect myself while flying?

      If air travel is unavoidable, there are some steps you can take to protect yourself. Most important: Wash your hands often, and stop touching your face. If possible, choose a window seat. A study from Emory University found that during flu season, the safest place to sit on a plane is by a window, as people sitting in window seats had less contact with potentially sick people. Disinfect hard surfaces. When you get to your seat and your hands are clean, use disinfecting wipes to clean the hard surfaces at your seat like the head and arm rest, the seatbelt buckle, the remote, screen, seat back pocket and the tray table. If the seat is hard and nonporous or leather or pleather, you can wipe that down, too. (Using wipes on upholstered seats could lead to a wet seat and spreading of germs rather than killing them.)

    • Should I wear a mask?

      The C.D.C. has recommended that all Americans wear cloth masks if they go out in public. This is a shift in federal guidance reflecting new concerns that the coronavirus is being spread by infected people who have no symptoms. Until now, the C.D.C., like the W.H.O., has advised that ordinary people don’t need to wear masks unless they are sick and coughing. Part of the reason was to preserve medical-grade masks for health care workers who desperately need them at a time when they are in continuously short supply. Masks don’t replace hand washing and social distancing.

    • What should I do if I feel sick?

      If you’ve been exposed to the coronavirus or think you have, and have a fever or symptoms like a cough or difficulty breathing, call a doctor. They should give you advice on whether you should be tested, how to get tested, and how to seek medical treatment without potentially infecting or exposing others.

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David Montefiori, a virologist at Duke University, said that he was involved in a new analysis, led by Dr. Korber, addressing those concerns. As part of that work, he said, his team at Duke had found lab results that were very similar to those of the Scripps Research scientists: Viruses with the D614G mutation infected cells more efficiently than those without it. He said the full paper has been submitted to a journal.

In the new research, the team led by Dr. Choe and Dr. Farzan performed two experiments. In one, they created harmless proxy viruses using standard tools, including retroviruses and so-called virus-like particles. Each was engineered to have the signature corona “spike” proteins that allow it to fasten to the surface of cells like Velcro.

The scientists found that viruses with the D614G mutation were more resilient, preserving about five times more functional spike proteins to infect cells than viruses without that mutation.

In another experiment, they found that viruses carrying the D614G mutation infected tissue cells far more efficiently than viruses without the mutation. Dr. Farzan said that the difference probably stems from a biological property of the mutation that confers more flexibility to the spike protein and stabilizes it.

Coronavirus vaccines, once developed, should work as well against the D614G variant as they do against others, the researchers said.

Outside experts said the new study, while impressive, left more work to be done. Michael Letko, an assistant professor in the Laboratory of Functional Viromics at Washington State University, said that other biological factors could also influence the spread of the virus in the real world. “We focus on the part of the virus we know the best, the spike, but we don’t know as much about how other parts work,” he said.

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Still, Dr. Letko said, the new research was convincing in demonstrating that viruses with the D614G mutation were more infectious in the lab.

Experts said the next step in determining if there are differences in real-world transmission is to test different variants in animals.

“That’s the incredible thing about viruses,” Dr. Letko said. “They’re called Darwinian machines, and these small changes can amplify quite dramatically. These small gains can be just enough to allow a virus to outcompete another virus that doesn’t have these things.”

NYT > Health