Who goes there? Novel complex senses viral infection

Double-stranded (ds) RNA viruses are a diverse group of viruses that include rotaviruses, a common cause of gastroenteritis. The ability of the immune system to detect and destroy viruses is critical for human health and survival. Now, a study published by Cell Press in the June 23rd issue of the journal Immunity identifies a novel sensor that is necessary to activate the immune response to viral infection. The research enhances our understanding of the complex and overlapping mechanisms our immune cells use to thwart infection.

Viruses are infectious agents composed of nucleic acid (DNA or RNA) and a protective protein coating. Viruses infect all types of organisms and can hijack host cell machinery to replicate (make many copies of themselves). The is the body's first line of defense against viruses and detects infection by sensing viral . Detection of a virus leads to activation of the type 1 interferon (IFN) response, a powerful weapon that is named for its ability to "interfere" with .

"During the past decade, major efforts using genetic approaches have identified three major classes of innate immune receptors for sensing microbial nucleic acids," says senior study author, Dr. Yong-Jun Liu from the University of Texas MD Anderson Cancer Center. "However, there is a major gap in our understanding of how these receptors bind nucleic acids and whether additional receptors or coreceptors exist. For example, Toll-like receptor 3 (TLR3) has been known as the only TLR that sense dsRNA and use adaptor molecule TRIF to trigger antiviral immune responses. Intriguingly, macrophages and from TLR3-deficient mice but not from TRIF-deficient mice could still make significant antiviral IFN responses to dsRNA, suggesting the presence of additional TRIF-dependent dsRNA sensors"

Dr. Liu and colleagues investigated this issue by isolating and characterizing proteins that bound to a synthetic form of double-stranded called poly I:C. Looking inside myeloid dendritic cells that are known to play a key role in pathogen detection, the researchers found two known dsRNA sensors as well as a previously unknown viral sensor that consists of three RNA helicases, DDX1, DDX21 and DHX36, and the adaptor molecule TRIF. This multi-helicase-TRIF complex bound directly to poly I:C and triggered an immune response. Dr. Liu's team went on to show that DDX1 directly bound to poly I:C while DDX21 and DHX36 served as bridges to TRIF and that each of the four components was essential for the appropriate immune response. Importantly, interference with the complex impaired the to influenza A and a type of rotavirus.

"Our study suggests that the DDX1-DDX21-DHX36 complex represents the missing poly I:C sensor and may represent an early sensor of poly I:C that triggers initial IFN production," concludes Dr. Liu. "This initial IFN production may help to activate other know dsRNA sensors which will serve to further amplify the IFN response. This may explain the overlapping functions of the known dsRNA sensors." A better understanding of the complex mechanisms our uses to detect viruses will contribute to the future design of more effective antiviral therapeutics.

Related Stories

Viral replicase points to potential cancer therapy

Mar 28, 2011

Alpha viruses, such as Sindbis virus, carry their genetic information on a single strand of RNA. On infection they use a protein, replicase, to produce double stranded RNA (dsRNA) which is used as genetic material to make ...

Researchers discover how cells recognize viral toxin

Mar 25, 2010

(PhysOrg.com) -- For many years it's been known that the fever, achiness and other symptoms you feel during the flu are triggered by a viral molecule that travels through the body acting like a toxin.

Recommended for you

Student seeks to improve pneumonia vaccines

22 hours ago

Almost a million Americans fall ill with pneumonia each year. Nearly half of these cases require hospitalization, and 5-7 percent are fatal. Current vaccines provide protection against some strains of the ...

Seabed solution for cold sores

Aug 20, 2014

The blue blood of abalone, a seabed delicacy could be used to combat common cold sores and related herpes virus following breakthrough research at the University of Sydney.

Better living through mitochondrial derived vesicles

Aug 19, 2014

(Medical Xpress)—As principal transformers of bacteria, organelles, synapses, and cells, vesicles might be said to be the stuff of life. One need look no further than the rapid rise to prominence of The ...

Zebrafish help to unravel Alzheimer's disease

Aug 19, 2014

New fundamental knowledge about the regulation of stem cells in the nerve tissue of zebrafish embryos results in surprising insights into neurodegenerative disease processes in the human brain. A new study by scientists at ...

User comments