MICROBIOLOGY Going Viral: Exploring the Role Of Viruses in Our Bodies

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CREDITS: ADAPTED FROM OMAR JABADO AND W. IAN LIPKIN; (PHOTO) CDC

Nucleotide sequences

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MICROBIOLOGY

adults. These volunteers were sequestered for

Going Viral: Exploring the Role

10 days and fed either a high-fat or a low-fat diet, and the researchers analyzed their stool samples for bacteria and viruses.

Of Viruses in Our Bodies

Overall, the median number of different kinds of phages was 44 per sample, Bush-

man reported at the meeting. But within

`Virome' surveys reveal our vast number and variety of viruses

24 hours of a person starting the new eating

regimen, the community of phages and bac-

VANCOUVER, CANADA--In the past decade, more diverse than the bacterial communities teria began changing. Because the phages

scientists have come to appreciate the vast within the same individuals. But each per- live in the bacteria, one would expect the

bacterial world inside the human body. They son's viral community remained stable over number and kinds of bacteria and phages to

have learned that it plays a role in regulating the course of the year.

change in parallel, but that was not always

the energy we take in from food, primes the WU microbiologist Kristine Wylie and the case, Bushman noted. There was also a

immune system, and performs a variety of her colleagues have begun to look at how the lot of variation between individuals, with

other functions that help maintain our health. virome may influence health, in particular the number of viral types differing by as

Now, researchers are gaining similar respect what role it might play in unexplained fevers much as 40-fold in the samples. But in those

for the viruses we carry around.

in infants. For children under 900,000

For a start, the variety and sheer number 3, fevers are the most common

of viruses that inhabit us put our bacterial companions to shame. Many of the viruses prey on the bacteria in our bodies, altering their numbers and diversity and shuffling genes--including genes for antibiotic resistance--from one bacterium to another. "Ultimately, those viruses are incredibly important in driving what's going on" in the human microbiota, says Curtis Suttle, a virologist at

cause of emergency room visits, but almost 90% of the time there's no clear cause for the high temperatures.

Wylie, Weinstock, WU's Gregory Storch, and their colleagues sequenced the DNA obtained from nasal swabs or blood plasma of 151 individuals,

800,000 700,000 600,000 500,000 400,000 300,000

Growth of Viral Database

Retroviridae Orthomyxoviridae Flaviviridae Hepadnaviridae Picornaviridae Paramyxoviridae Herpesviridae Other (59 Families)

the University of British Columbia (UBC), about half of whom had unex- 200,000

Vancouver, in Canada. "To understand the plained fevers. The team esti- 100,000 bacteria associated with humans, you can't mated there were 10,000 viral

do that without looking at the viruses as sequences in the plasma samples well," he says. Studies presented here at the of the children with fever and

0 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004 2006 2008

Year

International Human Microbiome Congress only about 1000 in healthy chil- Expanding universe. The tally of known viruses is exploding,

earlier this month have begun to do just that. dren. Some of the viruses found and this graph doesn't even include the incredible number that

One provocative, albeit preliminary, find- were common human pathogens, prey on bacteria.

ing has already emerged: Infants with unex- such as herpes and cold viruses.

plained fevers harbor many more viruses But there also seem to be unusual viruses, people eating the same foods, the repertoire

than healthy infants.

including an astrovirus, in the mix, Wylie of viruses tended to converge.

For years, virologists have documented reported. "There were new isolates that you These studies drive home that the human

specific viral infections, including HIV and might not have thought would be associated virome needs to be studied more closely,

SARS, by detecting identifiable viral DNA with febrile illness," says Frederic Bushman, Suttle says. But there are many challenges.

within blood or other tissues. But to do a a virologist at the University of Pennsylvania. For one, most of the viral sequences that

comprehensive survey of the viruses in the Much more work is needed to establish have turned up so far don't have matches

body--the so-called virome--"is a true fron- that any of these viruses explain the fevers, in any known databases, so the viruses

tier," says B. Brett Finlay, a microbiologist at but proving that could mean fewer anti- can't be characterized. And all the virome

UBC Vancouver. Last July, Jeffrey Gordon, biotics for infants, Wylie points out. To be survey techniques have their drawbacks.

a microbiologist at Washington University on the safe side, physicians tend to prescribe Bushman filtered out all the human and bac-

(WU) School of Medicine in St. Louis, and antibiotics for unexplained fevers, but such teria cells and cleared out all nonviral DNA

his colleagues described one such effort in a drugs are ineffective against viruses.

before sequencing any remaining DNA in his

group of seemingly healthy people. They iso- While Wylie has focused on the viruses samples. "What [that approach] probably

lated and characterized the viromes of adult that infect human cells, Bushman has homed does is throw out most of the virus that was

identical twins and their mothers, sampling in on the bacteriophages, viruses that attack there," Suttle says. Wylie and her colleagues,

stools for viral genetic material three times bacteria. For every bacterium in our body, on the other hand, sequenced all of the DNA

over the course of a year. The overall conclu- there's probably 100 phages, with an esti- in the stool samples and used computer pro-

sion: Healthy people "are full of viruses," mated 10 billion of these viruses packed into grams to sort sequences into human, bacte-

says WU's George Weinstock.

each gram of human stool. As part of a study rial, and viral bins. But with that strategy, "you

By one measure, the number of distinct of the interplay of diet, human gut microbes, usually wind up with a big bin of unknown

viruses in the stool samples ranged from 52 to and Crohn's disease, an inflammation of the [sequences]," Suttle adds. Bottom line, says

2773. The viromes varied significantly from digestive system, Bushman and his colleagues WU's Herbert "Skip" Virgin, "Bacteria are

one individual to the next; they were even have looked at the viromes of six healthy easier to count."

?ELIZABETH PENNISI

SCIENCE VOL 331 25 MARCH 2011

Published by AAAS

1513

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