When body meets H1N1 flu

Pandemic H1N1 influenza may seem daunting, but two new studies reveal that you’ve got it in you to fight the flu.

Two separate research teams have cataloged interactions between the H1N1 influenza virus and human cells, with one group reporting that human cells already contain powerful antiflu agents that also help defend against other viral infections, including West Nile virus and dengue.

Published online December 17 in Cell, both studies may help scientists build better flu-fighting therapies in the future.

One of the studies concentrated on learning how the body responds to the flu, says Stephen Elledge, a Howard Hughes Medical Institute investigator at Brigham and Women’s Hospital and Harvard Medical School in Boston. Elledge and Abraham Brass led the study, which identified more than 120 human genes required by the H1N1 virus to infect a cell. For most of the genes, their removal stopped or slowed virus growth. But for three of the genes, removal actually helped the virus grow better, indicating that those genes are normally involved in fighting the virus.

These three genes encode proteins in a family called the interferon-inducible transmembrane family, or IFITM proteins. The proteins IFITM1, IFITM2 and IFITM3 are normally made at low levels in cells. Scientists knew that an immune-stimulating protein called interferon causes IFITM levels to rise, but haven’t known what increased levels of those proteins does for the cell.

Now, Brass, Elledge and their colleagues show that IFITM proteins help kill flu viruses, and that IFITM3 may be particularly important. That protein may help block flu viruses from entering host cells, though the team has not pinpointed the mechanism. IFITM3 also thwarts viruses such as dengue, West Nile and yellow fever, the team found.
“This [protein] blocks them all,” Elledge says. Increasing levels of IFITM3 might boost the body’s ability to combat the flu. And the team shows that blocking the protein in chicken and dog cells used to grow vaccine strains could make the virus grow better, possibly speeding vaccine development, he says.

If people have varying levels of IFITM3 in their cells, people with low levels may be more susceptible to flu, speculates Andrew Mehle, a virologist at the University of California, Berkeley. He also wonders whether a species’ versions of the IFITM proteins may determine which viruses can infect that species.

The other Cell paper documents the hundreds of interactions between the H1N1 virus and host proteins that take place during an infection. Previously scientists have studied how individual virus proteins interact with human cells. The new, large-scale screen reveals that the H1N1 flu virus’ 10 proteins connect to 1,754 human proteins in some way, report researchers led by Aviv Regev and Nir Hacohen of the Broad Institute of MIT and Harvard in Cambridge, Mass. Of those relationships, 87 are direct between flu and human proteins. Indirect connections make up the remainder and include some interactions that affect levels of human proteins in a cell.

On average, one influenza protein interacts with about twice as many human proteins as does one typical human protein with other human proteins, says Regev. The flu virus “really is sending many tentacles into the cell,” giving the virus a big impact on a host cell’s behavior, she says.

Both studies raise intriguing questions, Mehle says. “They both seem to lay the foundation for several careers right now,” he says. “It will be pretty exciting for the field to chase down these leads over the next two or three years.”