Colorful character. The influenza virus makes itself at home in human cells and hijacks our proteins for its own ends.


Revoking Flu's Enemy-With-Benefits Status

Humans are the influenza virus's best friend. We give it a home. We take it on trips and introduce it to new people. We also provide the nasty invader with hundreds of our own proteins to help it enter our cells and copy itself, as a new study in Nature and two in Cell show. While this may seem like bad news for us, researchers hope that a better understanding of how we aid and abet the enemy will make the virus easier to stop.

Together, the three studies map the complicated interactions between viral and host genes, an accomplishment achieved for few other viruses to date. But this is just a first draft, and the findings from the different labs are both illuminating and confusing. "All three studies are fantastic," says Sumit Chanda, a systems biologist at the Burnham Institute for Medical Research in San Diego, California, who headed a team that published one of the reports online 21 December in Nature. "But each brings weaknesses and strengths to the table."

The three labs together identified several hundred human genes that influenza hijacks for its own benefit, but in most cases the groups each hit on different ones: Only about 30 genes overlap, an outcome that's "very surprising," says Peter Palese, a virologist at Mount Sinai School of Medicine in New York City, who co-authored the paper with Chanda. The two related studies that appeared online 17 December in Cell were led by Stephen Elledge at Brigham and Women's Hospital in Boston and Sagi Shapira and Nir Hacohen of the Broad Institute in Cambridge, Massachusetts.

Still, even these divergent findings open the door to attacking influenza virus by targeting host proteins rather than the unwanted visitor itself. Current antiviral drugs against influenza, like Tamiflu, cripple critical proteins in the virus itself, but influenza often develops resistance to them. A better strategy might be to focus on how human cells offer influenza a cozy home. "It would be very difficult for the virus to develop resistance against a therapy that targets a cellular protein," says Palese.

But first researchers have to identify the most important proteins and sort out the discrepancies between the three groups. Elledge's and Chanda's teams used the same basic technique to determine which human genes matter. They mixed the virus with human cells and then shut off human genes one at a time with so-called RNA interference. That revealed specific contributors to influenza's well-being. They are now sharing their raw data, hoping to sort out how their different experimental conditions may have led to the discrepant results.

The third study, led by Broad's Shapira and Hacohen, used a completely different strategy, analyzing interactions between human and viral proteins, as well as expression levels of different genes. This "multilayered" approach provides more of a big-picture look at the host-pathogen dance than the finer grained results of the RNA interference studies.

One of the more intriguing findings came out of a choice in Elledge's lab to hunt for human proteins that interfere with influenza virus replication, as opposed to those that assist it. Elledge, who collaborated with Abraham Brass of Massachusetts General Hospital in Boston, found an entire family of these, called interferon-inducible transmembrane proteins. These IFITMs exist in many other species, and Elledge suggests that removing them from chicken embryos or animal cells that are used to make influenza vaccines may greatly boost vaccine production by allowing the virus to make more copies of itself. Comparing levels of these IFITMs in different people could also explain why some people are much more susceptible to influenza viruses.

Memo to influenza: You're no friend, and your benefits may be about to expire.