Virus Sleuths Chip Away At Ebola Mysteries
Vincent Racaniello, who studies viruses at Columbia University, says Ebola has recently become his obsession.
"I find myself reading incessantly about Ebola when I should be doing other things," says Racaniello, host of the online show This Week in Virology, which has devoted several recent programs to Ebola.
The unprecedented Ebola outbreak probably has more virologists thinking about Ebola than ever before. And while scientists have learned a lot about this virus since it was discovered almost four decades ago, there's still a lot left to wonder about.
Racaniello and his virologist buddies wish they knew some really basic things — like, how does the virus actually slip into cells? What part of the cell's surface does it latch onto to get access? Knowing that might let scientists figure out ways to block it.
And how do outbreaks of Ebola actually start? "This is a really important question," says Racaniello,"because if we could figure out where the virus comes from we might be able to take measures to stop that."
Scientists believe the virus circulates in fruit bats, which seem to carry Ebola without getting sick. But no one knows the details of how bats pass it to humans or other species.
"We know for sure that gorillas and chimpanzees and some antelope have been infected with Ebola in the past," says veterinarian and epidemiologist Jonathan Epstein of EcoHealth Alliance, an organization devoted to understanding and predicting the emergence of diseases. "But the mechanism for spillover isn't totally clear, and so that's an area where more study needs to be done."
Here's another issue that needs more study: Once the virus finds its way into people, why is it that some people get very sick, others seem to get less sick, and others may not get sick at all?
Angela Rasmussen, a microbiologist at the University of Washington in Seattle, says we don't yet know of any genes that might influence someone's response to this virus.
"Prior to this outbreak in West Africa, there really haven't been that many human patients with Ebola, so these studies haven't really been conducted in people," Rasmussen says.
She and some colleagues have started to study this aspect of Ebola infection in mice. In a secure lab, they infected dozens of genetically diverse mice with the same Ebola virus. And in this week's issue of the journal Science, they report that they saw a wide range of disease outcomes, all the way from mild to severe illness — suggesting that the genetic makeup of individual mice played a huge role in how sick they got.
Rasmussen says there were key differences in genes that affect blood vessels. "We think that those genes may be implicated in Ebola pathogenesis," she says, "but we're still in the process of conducting studies on enough mice to be able to say that definitively."
Besides genes, scientists wonder what else might affect who lives and who dies. Robert Garry, a microbiologist at Tulane University, is part of a team that published an analysis Thursday in the New England Journal of Medicine that looks at people who got Ebola in Sierra Leone. He says it turns out that a person's age really mattered — with people under 21 having a much better chance of survival than people over 45. The researchers are not sure why — it may have something to do with differences in their immune systems.
And even though Ebola is known as a hemorrhagic fever, bleeding appears to be rare in this outbreak — the team only saw it in one patient in this study. That means it looks like this West African variant of the virus is different from the ones that have been seen in Central Africa in the past. "It's something that we need to examine further to try to see what these differences are in terms of the viral biology," says Garry.
Another big question is how the virus might mutate as it moves through large numbers of people, as it is now doing in West Africa. Could it become more or less deadly? Racaniello says there are examples of other viruses that changed over time to cause milder illness.
"But for the most part, most of the major viruses we know — AIDS/HIV-1, influenza, polio, measles — they all keep their virulence at pretty much the same level," Racaniello says. "Although you could argue we've only been studying them a short time."
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Transcript
RENEE MONTAGNE, HOST:
As with many events, the most unsettling aspect of the Ebola virus is the unknown. We're fortunate that researchers do know a lot about Ebola and procedures to contain an outbreak. Still, there remains a lot they don't know. NPR's Nell Greenfieldboyce has been talking with scientists who want to find out more.
NELL GREENFIELDBOYCE, BYLINE: The unprecedented Ebola outbreak has more virologists thinking about Ebola than ever before. Vincent Racaniello studies viruses at Columbia University.
VINCENT RACANIELLO: I find myself reading incessantly about Ebola when I should be doing other things.
GREENFIELDBOYCE: He gets a lot of questions, too. People ask him how Ebola might mutate as it moves through large numbers of people, as it's doing now in West Africa. Could it become more or less deadly? Racaniello says there are examples of other viruses that changed over time to cause milder illness.
RACANIELLO: But for the most part, most of the major viruses we know - AIDS, HIV-1, influenza, polio, measles - they all keep their virulence at pretty much the same level, although you could argue we've only been studying them a short time.
GREENFIELDBOYCE: He and his virologist buddies wish they knew some really basic things about Ebola, like how does the virus actually slip into cells? What part of the cell surface does it latch onto to get access? Knowing that might let scientists figure out ways to block it. And how do outbreaks of Ebola actually start?
RACANIELLO: This is a really important question because if we could figure out where the virus comes from, we might be able to take measures to stop that.
GREENFIELDBOYCE: Scientists believe the virus usually circulates in fruit bats. They seem to carry Ebola without getting sick. But no one knows the details of how bats pass it on to humans or other animals. Jonathan Epstein is an epidemiologist with EcoHealth Alliance, an organization devoted to understanding and predicting the emergence of diseases.
JONATHAN EPSTEIN: We're still trying to understand fully how other animals might get Ebola virus from bats. In other words, we know for sure that gorillas and chimpanzees and some antelope have been infected with Ebola in the past. But the mechanism for spillover isn't totally clear. And so that's an area where more study needs to be done.
GREENFIELDBOYCE: Does it spill over into people directly from bats, or from other infected animals or both? And once the virus finds its way into people, why is it that some people get very sick, others seem to get less sick and others may not get sick at all? Angela Rasmussen is at the University of Washington in Seattle. She says we don't yet know of any genes that might influence someone's response to this virus.
ANGELA RASMUSSEN: And in fact, prior to this outbreak in West Africa, there really haven't been that many human patients with Ebola, so these studies haven't really been conducted in people.
GREENFIELDBOYCE: She and some colleagues have started to study this in mice. They report on the work this week in the journal Science. In a secure lab, they infected dozens of genetically diverse mice with the same Ebola virus. They saw a wide range of disease outcomes, all the way from a mild to severe illness, showing that the genetic makeup of individual mice played a huge role in how sick they got. Rasmussen says that there were key differences in genes that affect blood vessels.
RASMUSSEN: So we think that those genes may be implicated in Ebola pathogenesis, but we're still in the process of conducting studies on enough mice to be able to say that definitively.
GREENFIELDBOYCE: Besides genes, scientists wonder what else might affect who lives and who dies. Robert Garry is a microbiologist at Tulane University. He and some colleagues have just published an analysis in the New England Journal of Medicine that looks at people who got ill in Sierra Leone. They found that a person's age really mattered. Fifty-seven percent of people under the age of 21 died. That's not good, but Garry says for older people, it was even worse.
ROBERT GARRY: If you were over 45, the case fatality rate was 94 percent, so a very small chance of surviving.
GREENFIELDBOYCE: They're not sure why. It may be something to do with the differences in their immune systems. And even though Ebola is a hemorrhagic fever - it's associated with bleeding - Garry says bleeding was rare in their study. They only saw it in one patient. He says it looks like this West African variant of the virus is different than the ones that have been seen in central Africa in the past.
GARRY: It's something that we need to examine further to try to see what the differences are in terms of the viral biology.
GREENFIELDBOYCE: That's just one example of how this outbreak, the largest ever, is an opportunity to get answers that might help scientists be better prepared to fight Ebola in the future. Nell Greenfieldboyce, NPR News. Transcript provided by NPR, Copyright NPR.
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