Very interesting science stuff about the Alpha COVID-19 variant:
How the ‘Alpha’ Coronavirus Variant Became So Powerful
How the ‘Alpha’ Coronavirus Variant Became So Powerful
A new study suggests how the variant first identified in Britain hides from the human immune system. Its stealth may be part of its success.
In December, British researchers discovered that
a new variant was sweeping through their country. When it arrived in other countries, the variant, now known as Alpha, tended to become more common in its new homes as well. By April, it had become
the dominant variant in the United States, and it has remained so
ever since.
Alpha’s swift success has left scientists wondering how the variant conquered the world. A
new study points to one secret to its success: Alpha disables the first line of immune defense in our bodies, giving the variant more time to multiply.
“It’s very impressive,” said Dr. Maudry Laurent-Rolle, a physician and virologist at the Yale School of Medicine who was not involved in the new study. “Any successful virus has to get beyond that first defense system. The more successful it is at doing that, the better off the virus is.”
The report was posted online on Monday and has not yet been published in a scientific journal.
Alpha has 23 mutations that set it apart from other coronaviruses. When the variant started to surge in Britain, researchers began inspecting these genetic tweaks to look for explanations as to why it was spreading faster than other variants.
A lot of researchers focused their attention on the nine mutations that alter the so-called spike protein that covers the coronavirus and allows it to invade cells. One of those mutations helps the virus bind more tightly to cells, potentially improving its chances of a successful infection.
But other scientists have focused on how Alpha affects the human immune response. Gregory Towers, a virologist at the University College London, and his colleagues grew coronaviruses in human lung cells, comparing Alpha-infected cells with those infected with earlier variants of the coronavirus.
They found that lung cells with Alpha made drastically less interferon, a protein that switches on a host of immune defenses. They also found that in the Alpha cells, the defensive genes normally switched on by interferon were quieter than in cells infected with other variants.
Somehow, the immune system’s most important alarm bells were barely ringing in the presence of the Alpha variant. “It’s making itself more invisible,” Dr. Towers said.
To investigate how Alpha achieved this invisibility, the researchers looked at how the coronavirus replicated inside of infected cells. They found that Alpha-infected cells make a lot of extra copies — some 80 times more than other versions of the virus — of a gene called Orf9b.
“It’s off the chart,” said Nevan Krogan, a molecular biologist at the University of California, San Francisco, and a co-author of the new study.
In
previous research, Dr. Krogan and his colleagues had found that Orf9b makes a viral protein that locks onto a human protein called Tom70. And it just so happens that Tom70 is essential for a cell’s release of interferon in the face of an invading virus.
Putting all of the evidence together, Dr. Krogan and his colleagues argue that the Alpha variant carries a mutation that forces the production of a lot more Orf9b proteins. Those proteins swarm the human Tom70 proteins, dampening the production of interferon and a full immune response. The virus, protected from attack, has better odds of making copies of itself.
An infected cell can gradually remove the Orf9b proteins from its Tom70 molecules, however. By about 12 hours after infection, the alarm system starts coming back online. And because of that immune response, Dr. Towers said, “all hell breaks loose.”
Dr. Towers speculated that when the delayed immune response finally happens, people infected with Alpha have a more robust reaction than they would with other variants, coughing and shedding virus-laden mucus from not only their mouths, but also their noses — making Alpha even better at spreading.
“What they’re showing makes sense,” Dr. Laurent-Rolle said. But she would like to see more lines of evidence in support of their conclusion. For example, the scientists did not run a standard test to measure the number of Orf9b proteins.
“That’s one thing that could be concerning,” she said. Dr. Krogan said he and his colleagues were developing that test now.
Dr. Krogan’s team has also started similar experiments on other variants, including the variant first identified in South Africa, known as Beta, and the one first identified in India, known as Delta. The preliminary results surprised them.
Both Beta and Delta drive down interferon in infected cells. But there’s no sign that they do so by flooding the cells with Orf9b proteins. They may have independently evolved their own tricks for manipulating our immune system.
“They’re all turning down the immune response in different ways,” Dr. Krogan said.
Cecile King, an immunologist at the Garvan Institute of Medical Research in Sydney, Australia, who was not involved in the study, said that understanding how the virus was evolving these escapes would help scientists design better vaccines for Covid-19.
The current crop of vaccines direct the immune system to recognize spike proteins. But studies on people who recover naturally from Covid-19 have shown that their immune systems learn to recognize other viral proteins, including Orf9b.
A number of researchers are putting together combinations of coronavirus proteins into new vaccines. But they need to take caution, because some of the proteins may actually dampen immunity.
“It’s quite a tricky enterprise, but becoming more possible as we learn more,” Dr. King said.
nypost.com
