Nature Immunology pp 981 - 988

Research in the October issue of Nature Immunology identifying a new response factor triggered by intracellular sensors of many types of viruses may open up new ways of enhancing our ability to fight infections

Viral infections cause immune cells to fight back by making proteins called interferons, which are critical for effective activation of the body’s defense mechanisms. This new research gives scientists a novel direction for finding effective treatments for certain types of virus infection.

Many of the signals essential to interferon production have been characterized, and they emanate from myriad different participants. The abundance of such information might indicate that every important way of triggering interferon is known. Recent work has identified new sensors in cells that respond to viral production of double-stranded RNA molecules, but just how these new sensors caused interferon to be produced was unknown.

Shizuo Akira and colleagues have found that a protein they call interferon-beta promoter stimulator 1 (IPS-1) is essential for signaling by the new sensors for production of interferon. Cells that were deficient in IPS-1 made less interferon and were more susceptible to virus infection than normal cells. IPS-1 was identified by a 'brute force' method in which hundreds of candidate proteins were screened for the ability to trigger interferon production. The finding is of importance, as it represents one more potential weapon against the harsh assault viruses can make on our health.

Nature Immunology pp 1047 - 1053

Mice that express a particular protein in their lungs develop an asthma-like disease very similar to human asthma and other allergic inflammatory diseases. This new finding reported in the October issue of Nature Immunology opens up new ways of studying how disabling lung inflammation may be prevented.

Asthma is the most common serious chronic disease of childhood, affecting nearly five million children in the United States alone. The hallmarks of human asthma and allergy include increased numbers of immune cells in lung tissue. These cells are the key players responsible for secreting inflammatory factors that lead to the clinical symptoms associated with asthma. Many of the processes that subsequently lead to severe lung inflammation are known and most current treatments for allergy and asthma are aimed at blocking them. Unfortunately, most of these treatments only alleviate symptoms rather than prevent their underlying causes.

Steven Ziegler and colleagues provide clues that may allow treatments to prevent lung inflammation from occurring in the first place. The team studied a protein already known to be associated with inflammation, thymic stromal lymphopoetin (TSLP), to see if it was also responsible for symptoms of severe lung inflammation in mice. Mice that produced TSLP specifically in lung cells showed greatly increased disease that had most of the hallmarks of human asthma and other allergic inflammatory diseases. Zeigler and colleagues also evaluated mice that were deficient in TSLP, and these mice showed few signs of lung inflammation and failed to develop asthma-like disease.

Importantly, this work shows that a single protein is a key factor in the appearance of lung inflammatory disease, which may open up new avenues of research into treatments that prevent lung inflammation before the onset of debilitating symptoms.

Nature Immunology pp 995 - 1001

Scientists have identified a new defense mechanism by which cells try to repel viral invaders, as reported in the October issue of Nature Immunology. Viruses infect cells and 'hijack' host enzymes and basic building blocks to replicate themselves. To do so, viruses first gain entry into cells by fusing with the host cell’s membrane. But our immune system has also developed strategies to counteract this assault. Among these are proteins called defensins, which are often induced in response to viruses in the vicinity and can prevent the fusion of viruses with uninfected cells. Now scientists have made an important advance in understanding how defensins prevent viral fusion. This finding may lead to the development of new strategies for preventing and treating viral infections.

To understand the antiviral property of defensins, Leonid Chernomordik and colleagues studied a specific defensin called RC2 and found that it prevents infection of cells by many viruses, including influenza. On closer examination, RC2 seems to bind to the 'sugar' portions of proteins that reside in cell membranes. This process prevents the membrane from fusing with the virus, essentially producing a 'lockdown' of the cell membrane, preventing viral entry. The authors extended their observation to another family of 'sugar-binding' immune molecules called collectins, allowing potential for this antiviral strategy to be generalized and have a broad application.