Identifying the mechanism of transmission of virus DNA

The biggest technical challenge in gene therapy or DNA vaccine development, in which DNA is injected from the outside to treat diseases, is to accurately transfer DNA into the nucleus.

50-90% of the world’s population is chronically infected with the human giant cell virus (HCMV). Healthy people have no apparent symptoms, but infants may suffer from hearing loss and cerebral palsy disorders, and elderly people with weak immunity may suffer from cardiovascular disease and immunofunction deficiency. Considering the enormous socioeconomic costs required for the care and treatment of HCMV-related disabled children and elderly patients, the National Vaccine Advisory Committee has selected the HCMV vaccine as the number one vaccine to be developed as a priority. The second place was the all-around influenza vaccine.

Since the replication of the RNA viruses, corona and influenza, occurs in the cytoplasm, infection occurs when the genome RNA passes through the cell membrane. In contrast, since replication of DNA viruses such as HCMV occurs in the nucleus, DNA genes must pass through the cell membrane and then pass through the nuclear membrane obstacle again. Little is known about how viral DNA passes through nuclear pores present in nuclear membranes.

The research team, led by Professor Ahn Kwang-seok of the Department of Bioscience at Seoul National University, used HCMV as an experimental model and revealed that host protein STING plays a key role in nuclear transfer of viral DNA. STING plays an essential role in accurately docking the DNA into the nucleus after it is bound to the virus shell (capseed) that encloses the DNA and allowing it to escape into the nucleus. In cells with STING deficiency, viral DNA transport did not occur and successful infection failed.

The results of this study are expected to pave the way for the development of HCMV chronic infection treatments and further provide clues to “DNA delivery” technology innovation, the biggest obstacle to the development of gene therapy and DNA vaccines.

This study was conducted with the support of the RNA Research Group of the Institute of Basic Science and the Korea Research Foundation.

Reference Journal: Hong, Y., Jeong, H., Park, K., Lee, S., Shim, J. Y., Kim, H., Song, Y., Park, S., Park, H. Y., Kim, V. N., & Ahn, K. (2021). Sting facilitates nuclear import of herpesvirus genome during infection. Proceedings of the National Academy of Sciences, 118(33).

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