New Viral-Human Protein Interaction Discovery May Lead to New Antivirals

Researchers from the University of Texas at Austin have determined the function of an influenza virus protein in inhibiting a human antiviral protein in their work published in the journal Cell Host & Microbe on April 9.

Influenza A viruses, also commonly known as the flu, which, according to the authors, “cause an annual highly contagious respiratory disease in humans, infect many avian and mammalian species and are responsible for periodic human pandemics that can result in high mortality rates.” Influenza B and C types also exist, which have slightly different properties than influenza A. Due to the high prevalence of infection with the virus and concerns about deaths, research and treatments for this common affliction are important.

Influenza virus has been a human health concern for centuries. This picture is from the 1918 flu pandemic in Washington, D.C.

In this study, the scientists noted the importance of the viral protein NS1 in influenza A virus replication in humans, “a nonstructural protein that employs several strategies to inhibit the host antiviral response and regulates other cell and virus functions.” In other words, this protein had been found previously in other research to be important in preventing natural antiviral activities in cells. Many viruses encode proteins such as NS1 in their genetic material, which can consist of DNA (like humans and animals), or RNA, a close relative of DNA. These proteins help viruses battle against the host immune system which has the goal of eradicating all virus particle from the body.

Specifically, this study found that NS1 interacts with the host protein DDX21, an RNA helicase protein that functions in altering RNA. One of its functions is to interact with an influenza virus protein called PB1, which helps to prevent replication of the virus. NS1 functions in binding to DDX21, preventing it from interacting with PB1 and therefore allowing the virus to replicate. This discovery will allow scientists to attempt to develop new antivirals that target this interaction, since other antivirals against influenza A are beginning to see resistance developed against them due to the constantly changing influenza A.

Article: Chen G., Liu, C-H., Zhou, L., Krug, R.M. (2014). Cellular DDX21 RNA Helicase Inhibits Influenza A Virus Replication but Is Counteracted by the Viral NS1 Protein. Cell Host & Microbe, 15(4), 484-93.

Link: www.cell.com/cell-host-microbe/abstract/S1931-3128%2814%2900101-2

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