Science Signaling: These proteins have defeated emerging and recurring viruses

Scientists have discovered that a family of proteins known for reducing HIV infection may have an advantage over other emerging and re-emerging viruses

The key to their newly discovered power is to enhance the signal sent by immune cells and release one of the most powerful fighters in the innate antiviral response, a protein called type I interferon

Cell culture experiments have shown that the cell signaling activities of these proteins from the SERINC family help protect cells from HIV, Ebola and Zika virus infections

It is one thing for proteins to directly fight specific viruses, just as SERINC5 has been shown to incorporate HIV particles during virus production

"Viruses can bypass the direct antiviral effect," Liu said, "but if this protein can also regulate key pathways without directly acting on the virus, then the virus's ability to fight it may be limited

"If this family of molecules can do this in animals and humans, then you might wonder whether it can be used in a wide range of antiviral treatments

The research was published in the September 14th issue of "Science Signal"

Liu took what he called the "evolutionary arms race" of HIV and the human immune system for many years, and led a 2019 study that described a battle where the HIV protein Nef gene can prevail - especially by interfering with the SERINC virus Proteins that make cells

In this study, Liu and colleagues further studied the function of SERINC5 in target cells in the next stage of viral infection

SERINC5 itself does not regulate this signaling system-it binds to other proteins called MAVS and TRAF6

In the cell culture at the beginning of the virus infection, the researchers observed the transfer of SERINC5 from the cell surface to the outside of the membrane around the mitochondria (the power center of the cell), which is an unusual move

"The aggregation of these proteins means that they need each other-this is an exciting discovery that a large complex like this can recruit additional molecules and increase the efficiency of the signaling pathway

These recruited molecules are part of the cascade of messages that cause virus-infected cells to produce type I interferon and NF-kB inflammatory cytokines, both of which play a key role in limiting virus infection in the early stages

Conversely, when cells are modified so that they do not produce SERINC5 protein, these viruses take over the cells and replicate more—this shows how important SERINC plays a role in enhancing the host cell’s primary antiviral response

This study was conducted in two members of the SERINC family, SERINC3 and SERINC5, but Liu speculates that other versions may have similar effects

Liu is optimistic about whether the function of this protein can inhibit the new coronavirus

He said: "I guess the SERINC protein will have an effect, because we know that type I interferon is so important to control the virus in the early stage, and this molecule can enhance the type I interferon response
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" "Find a protein that can The key way to regulate a broad antiviral effect-well, you can imagine that this protein has a broad antiviral function
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SERINC proteins potentiate antiviral type I IFN production and proinflammatory signaling pathways