Influenza mechanism that interferes with antiviral host responses found
The study, which appears in the journal Nature, demonstrates that the NS1 protein, an immunosuppressive, of the influenza A virus is capable of hijacking key antiviral gene function regulators by mimicking their genetic components, according to NewsWise.com.
The scientists hope that the results of their work will have a major impact on the understanding of the biology of seasonal influenza and its pathogenesis. The research may also lead to a possible target for an entirely new class of antiviral, as well as anti-inflammatory, medications.
The research shows that the viral NS1 protein contains the same amino acid sequence as the "tail" domain of human histone H3, a DNA packaging protein. Histones located in the cell nucleus play a role in gene activation. Chemical changes within the histone "tails" allow effector proteins to be recruited, which determines which genes are turned on or off.
"By mimicking the histone H3 tail, the NS1 tail gives the virus access to the core of gene regulating machinery," first author Ivan Marazzi said, NewsWise.com reports. "Through this mimicry the virus targets a set of proteins in the nucleus of the infected cells and impairs the anti-viral host cell response."
Marazzi and a colleague, graduate student Jessica Ho, discovered that the NS1protein can track and target a protein complex called PAF1C. The PAF1C complex is essential for expressing the genes that are critical in the human antiviral response.
"NS1 is hijacking PAF1C and using its similarity with the H3 'tail' to gain access to a position in the genome that helps the virus to block antiviral genes," Ho said, NewsWise.com reports. "This finding extends the known ability of pathogens to reveal key regulatory processes and to use them for the pathogen's advantage."