Experiments in cell culture have shown that the cell signaling activity of these proteins from the SERINC family helps protect cells from infection with HIV, Ebola, and decaviruses. Researchers are currently testing whether this feature is also effective against SARS-CoV-2, the virus that causes COVID-19.
Since SERINC5 has been shown to act by incorporating itself into HIV particles during virus production, it is one thing that the protein acts directly on a particular virus.However, revealing that proteins have an enhancing effect on essential antiviral cell signaling pathways during host cell infection is completely different, the senior research author said. Shan Lu Liu, Professor of virology Ohio State University Faculty of Veterinary and Biological Sciences..
“The virus can circumvent the direct antiviral effect,” said Liu, a researcher and deputy director at Ohio State University. Retrovirus Research Center.. “But if this protein can also regulate important pathways without acting directly on the virus, the virus may have limited ability to counteract it.
“If this molecular family could do this in animals and humans, we might wonder if it could be used in a wide range of antiviral therapies.”
The study was published in the journal today (September 14, 2021) Scientific signaling..
Liu led 2019 by studying what is called an “evolutionary arms race” between HIV and the human immune system over the years. study It explained how an HIV protein called Nef can gain an edge in the fight, especially by interfering with the SELINC protein in virus-producing cells.
In this study, Liu et al. Investigated the function of SELINC5 in target cells during the next viral infection stage. In addition to enhancing the signal that produces type I interferon, they found that SELINC5 has the same effect on the signal that produces NF-kB inflammatory cytokines, another component of the early antiviral response. bottom.
Rather than regulating this signaling system alone, SERINC5 works with other proteins called MAVS and TRAF6. But some of its exact behavior is still a mystery, Liu said.
In cell cultures where viral infections began, researchers observed that SELINC5 migrated from the cell surface just outside the membrane around the cell’s power center, the mitochondria. This is an unusual move. Once there, SELINC5 worked with MAVS and TRAF6 to form a large, multifaceted complex. This seems to explain why that role has a great influence on what happens next in the signaling pathway.
“Aggregation of these proteins means they need each other-and this is an exciting discovery,” said Liu, also co-director. Viruses and new pathogens Ohio State University Program Infectious Diseases Research Institute.. “Such large complexes can mobilize additional molecules to increase the efficiency of signaling pathways.”
These mobilized molecules are part of a cascade of messages that lead to type I interferon production and NF-kB inflammatory cytokines from virus-infected cells, both of which play important roles in limiting viral infection in the early stages. Play. In experiments using cell cultures of multiple types of humans and animals, this mechanism was found to inhibit cell infection by HIV, Ebola, and Zika virus.
In contrast, when cells were modified to not produce the SELINC5 protein, these viruses hijacked the cells and replicated more. This suggests how important SELINC’s role is in the process of enhancing the primary antiviral response of host cells.
This work was done on two members of the SERINC family, SERINC3 and SERINC5, but Liu speculated that other versions would have similar effects. However, there is still much to learn, such as what triggers SELINC5 to move from the cell surface to mitochondria and normal cell function in the absence of the virus.
Liu is optimistic about whether protein function can suppress the COVID-19 virus.
“My guess is that the SELINC protein works because type I interferon is very important for controlling the virus in the early stages, and we know that this molecule can enhance the type I interferon response. “He said. “If you find one protein that can regulate important pathways with a wide range of antiviral effects, you can imagine that this protein has a wide range of antiviral functions.”
This work was supported by the National Institute of Health and the National Cancer Institute (NCI).
Co-authors include Ohio State University’s Cong Zeng, Tianliang Li, Jingyou Yu, Yi-Min Zheng, Jacob Yount, Hatao Wen, and Abdul Waheed and Eric Freed of the NCI HIV Dynamics and Replication Program.
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