In-Depth: UC San Francisco team uncovers how the Alpha variant hides from immune defenses

Virus Outbreak Variant
Posted at 6:23 PM, Jun 10, 2021
and last updated 2021-06-10 23:38:55-04

SAN DIEGO (KGTV) -- The fast-spreading Alpha variant now accounts for two-thirds of the COVID infections in the United States, and researchers at the University of California, San Francisco have made a discovery that helps explain why.

The variant, known by the scientific name B.1.1.7, has swept across the world since it was first detected in the United Kingdom late last year.

According to a new UCSF study, the variant carries a genetic mutation that acts like a viral “smoke grenade,” temporarily hiding the virus from the immune system for several hours.

The mutation allows the Alpha variant to gain a head start on the body’s defenses, according to molecular biologist Dr. Nevan Krogan, a co-author of the study.

“In a very sneaky way, the virus is turning down the immune response, allowing the virus to grow more in our cells,” Krogan said. “This is a big reason, we think, of why we're getting increased transmissibility and ultimately increased mortality with this Alpha variant.”

The Centers for Disease Control and Prevention estimated Thursday the Alpha variant was responsible for 66 percent of the COVID infections in the U.S. from April 11 to April 24. That represents a massive increase since December, when the CDC estimated the variant accounted for just 0.2 percent of U.S. cases.

While much of the research on Alpha and other variants has focused on mutations in the spike protein, Dr. Krogan and his collaborators focused their efforts on genes buried inside the viral shell.

They discovered one, known as Orf9b, that churns out vast quantities of a protein once the virus enters a human cell. Those viral proteins effectively cloud the body’s alarm system like a smokescreen, Dr. Krogan said.

Earlier versions of SARS-CoV-2 produced some of this protein, but Alpha’s mutation allows it to generate up to 100 times more, the researchers found. This smokescreen effect lasted for about 12 hours in laboratory tests before cellular defenses kicked back in.

Dr. Krogan’s team has done preliminary research on the Beta and Delta variants, first identified in South Africa and India, respectively.

Both show signs of cloaking themselves from the body’s alarm system, a protein called interferon that turns on immune defenses. But those variants don’t use the same gene that Alpha does.

“There's a suppression of the immune system, so it's another smoke bomb. What is it?” Krogan said.

UCSF researchers have begun working to identify the mechanism in those variants, he said.

“The more we understand how the virus mutates to overcome our defense mechanisms and then manipulate us to increase transmissibility, the better off we're going to be in terms of finding new strategies to fight off infection,” he said.

The good news is that our vaccines still work against all these variants.

A new study from Public Health England showed two doses of the Pfizer vaccine was 93 percent effective against the Alpha variant and 88 percent effective against Delta.

But getting both doses is critical. After just one dose, the Pfizer vaccine was only 33 percent effective.