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Scientists Find How SARS Virus Infects Human Cells

Posted on: Friday, 16 September 2005, 09:00 CDT

Scientists find how SARS virus infects human cells

LOS ANGELES, Sept. 15 (Xinhua) -- The first detailed images of a piece of spike-shaped protein on the shell of the SARS virus have unveiled how the virus grabs host cells and initiates infection, scientists reported on Thursday.

The structure, which shows how the spike protein grasps its receptor, may help scientists learn new details about how the virus infects cells.

The information could also be helpful in identifying potential targets for novel antiviral drugs or vaccines, the researchers from the Harvard Medical School said in the Sept.16 issue of the journal Science.

The SARS, or Severe Acute Respiratory Syndrome, coronavirus was responsible for a worldwide outbreak in 2002-2003 that affected more than 8,000 people and killed about 800 before under control.

Public health experts worry about another outbreak of the virus, which originates in wild animals.

Prior to this studies, researchers knew that one of the key steps in SARS infection occurs when the virus's spike protein attaches to a receptor on the surface of target cells. Attachment of the spike protein permits the virus to fuse with a host cell and inject its RNA to infect the cell.

Thus a detailed understanding of how the spike protein complexes with its cell receptor, ACE2 (angiotensin-converting enzyme 2), could have important clinical implications, the researchers said.

"The interest in understanding this complex has to do with the fact that this virus jumps from animals to humans, and then among humans, " said Fang Li, a post-doctorate researcher at Harvard Medical School and first author of the paper.

The researchers created crystals of the relevant fragments of the spike protein in complex with the ACE2 receptor. Then they analyzed the structure of the crystallized protein complex using x-ray crystallography.

The x-ray structure revealed that the spike protein fragment showed a slightly concave surface that fits a complementary surface on the receptor, the researchers said.

The studies also revealed important new information about two specific amino acids that are most critical for determining how the SARS virus adapted from infecting only civets to infecting humans, Li told Xinhua in a telephone interview.

Both of these critical amino acids turned out to be right in the middle of the interface between the spike protein and the receptor. Even small mutations in the spike protein gene that alter the identity of amino acids at those sites can affect the virus's ability to infect humans.

A dramatic epidemiological difference can result from what looks like an almost trivial mutation. In human SARS virus, such mutations enable viral transmission by altering the shape of the spike protein, which affects how well it binds to the receptor, Li said.

"The mutation of one amino acid enables the SARS virus to jump from civets to humans, raising the virulence by tens of times. And another mutation enables viral transmission among humans," Li said.

These findings will not only help better understand how SARS virus infects people and how the SARS epidemic broke out in year 2002-03, but also provide the basis of a vaccine or therapy against SARS, Li said, noting that the threat of new SARS outbreak is still hanging over.

"The SARS appears to be under control now, but we can't overlook the danger of a new outbreak. We have not found the real wild reservoir of the virus yet, and the civet is only an interim reservoir."

"The virus may lurk in the wild until new mutations enable it to arouse a new pandemic," he said.

Source: Xinhua News Agency - CEIS

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