A finding by a team of scientists at the National Institutes of Health may account for why the flu virus is more infectious in cold winter temperatures than during the warmer months.

At winter temperatures, the virus's outer covering, or envelope, hardens to a rubbery gel that could shield the virus as it passes from person to person, the researchers have found. At warmer temperatures, however, the protective gel melts to a liquid phase. But this liquid phase apparently isn't tough enough to protect the virus against the elements, and so the virus loses its ability to spread from person to person.

The findings were published online March 2 in Nature Chemical Biology. The study was a collaboration between researchers at two NIH institutes, the National Institute of Child Health and Human Development, and the National Institute on Alcohol Abuse and Alcoholism.

"The study results open new avenues of research for thwarting winter flu outbreaks," said NICHD Director Duane Alexander. "Now that we understand how the flu virus protects itself so that it can spread from person to person, we can work on ways to interfere with that protective mechanism."

Influenza viruses are usually spread from person to person through coughs and sneezes. Infection with flu virus can cause mild to severe illness, and at times can lead to death.

In October of 2007, researchers working with guinea pigs showed that animals sick with the flu were more likely to get other guinea pigs sick at colder temperatures than at warmer temperatures.

In the current study, the NIH researchers used a sophisticated magnetic resonance technique, developed and previously tested in NIAAA's Laboratory of Membrane Biochemistry and Biophysics, to create a detailed fingerprint of how the virus's outer membrane responded to variations in temperature. The virus's outer membrane is composed chiefly of molecules known as lipids, explained the study's senior author, Joshua Zimmerberg, Ph.D., chief of NICHD's Laboratory of Cellular And Molecular Biophysics. This family of molecules does not mix with water, and includes oils, fats, waxes, and cholesterol.

Dr. Zimmerberg and his colleagues found that at temperatures slightly above freezing, the virus's lipid covering solidified into a gel. As temperatures approach 60 degrees Fahrenheit, the covering gradually thaws, eventually melting to a soupy mix.

Cooler temperatures, apparently, cause the virus to form the rubbery outer covering that can withstand travel from person to person, Dr. Zimmerberg said. Once in the respiratory tract, the warm temperature in the body causes the covering to melt to its liquid form, so that the virus can infect the cells of its new host, he added.

"Like an M&M in your mouth, the protective covering melts when it enters the respiratory tract," Dr. Zimmerberg said. "It's only in this liquid phase that the virus is capable of entering a cell to infect it."

In spring and summer, however, the temperatures are too high to allow the viral membrane to enter its gel state. Dr. Zimmerberg said that at these temperatures, the individual flu viruses would dry out and weaken, and this would help to account for the ending of flu season.

The finding opens up new possibilities for research, Dr. Zimmerberg said. Strategies to disrupt the virus and prevent it from spreading could involve seeking ways to disrupt the virus's lipid membrane.

In cold temperatures, the hard lipid shell can be resistant to certain detergents, so one strategy could involve testing for more effective detergents and hand-washing protocols to hinder the spread of the virus.

Similarly, Dr. Zimmerberg added that flu researchers might wish to study whether, in areas affected by a severe form of the flu, people might better protect themselves against getting sick by remaining indoors at warmer temperatures than usual.

Other authors of the paper were I.V. Polozov and L. Bezrukov, both of the Laboratory of Cellular And Molecular Biophysics at NICHD and K. Gawrisch of the Laboratory of Membrane Biochemistry and Biophysics, National Institute of Alcohol Abuse and Alcoholism. Magnetic resonance experiments were conducted and analyzed at NIAAA under Dr. Gawrisch's guidance.

The NICHD sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visit the Institute's Web site at http://www.nichd.nih.gov/.

The National Institute on Alcohol Abuse and Alcoholism, part of the National Institutes of Health, is the primary U.S. agency for conducting and supporting research on the causes, consequences, prevention, and treatment of alcohol abuse, alcoholism, and alcohol problems and disseminates research findings to general, professional, and academic audiences. Additional alcohol research information and publications are available at www.niaaa.nih.gov.

The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.