How does viral dsRNA provoke immune response?

Findings of a new study provide clues about antiviral immunity. The study, titled "SIDT2 Transports Extracellular dsRNA into the Cytoplasm for Innate Immune Recognition," appears in the prestigious journal Immunity.

Led by researchers from the University of Melbourne and Monash University in Australia and Harvard University in the USA, the study discovers that a protein called SIDT2 is required to transport viral dsRNA from the endosome into the cytoplasm for immune activation.

The discovery that the dsRNA transport activity of SIDT2 is essential for antiviral immunity would help to develop RNA-based medicines, the researchers hope.

In viral infection, the infected cell releases viral double-stranded RNA (dsRNA) into the environment (extracellular space). This dsRNA provokes innate immune responses.

No doubt, there is a race between virus and immune response. Viruses use multiple strategies to escape immune attacks and establish their infection in the body, whereas the body has measures to mount a rapid immune response that beat viruses.

Tan Nguyen, the study first author and a researcher at the University of Melbourne, noted that viral dsRNA normally does not exist in the human body, and human cells recognize this dsRNA as a sign of viral infection and launch an antiviral immune response.

However, there is still a question to be answered. Cells internalize, or engulf, materials in the extracellular space into the endosome, a specialized structure within cells. It remains elusive how viral dsRNA can escape the endosome and enter the cytoplasm, where it is recognized by the cell.

In this work, the researchers found that the protein SIDT2 transports dsRNA from the endosome to the cytoplasm, allowing for the activation of antiviral immune response. SIDT2-deficient mice were vulnerable to infections of EMCV and HSV-1. The production of antiviral cytokines was impaired in the animals.

These data provide new clues about how viral dsRNA triggers antiviral immunity and demonstrates a role of SIDT2 in dsRNA transport and innate immune recognition.

Ken Pang, a senior research officer at the Walter and Eliza Hall Institute who led the study, said that they also found that SIDT2 is important for uninfected cells to recognize the presence of viral RNA in the extracellular space. Therefore, uninfected cells may initiate antiviral immunity before being infected.

The researchers believe that the dsRNA transport activity of SIDT2 may be utilized to develop novel medicines.
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