Acute retinal necrosis (ARN) is caused by the alpha-herpesvirus subfamily, including herpes simplex virus type 1 (HSV-1). Some viruses use host-derived long non-coding RNA (lncRNA) for proliferation. Hence, we focused on lncRNA as a novel antiviral therapeutic target for ARN.
First, using 661W cells (murine photoreceptor cell line) infected by HSV-1, we comprehensively identified host-derived lncRNAs whose expression was induced after the infection. Of these lncRNAs, we focused on lncRNA U90926, which was also highly expressed in the retina of the murine ARN model. HSV-1 DNA replication and HSV-1 proliferation were remarkably suppressed in HSV-1 infected U90926-knockdown cells. In addition, the survival rates of U90926-knockdown cells after HSV-1 infection were significantly higher than those of the control cells.
Further, we identified the human U90926 gene that coded two transcripts (i. e., 1,955 and 592 bases) in the human genome. In the vitreous fluid of patients with ARN caused by HSV-1, the amount of longer human U90926 transcript was remarkably high. We found that the amount of transcript had a strong positive correlation with the vitreous humor viral load and final best-corrected logarithmic minimum angle of resolution (logMAR) visual acuity.
Considering these findings, lncRNA U90926 could be a potential novel therapeutic target for ARN caused by HSV-1.
Nippon Ganka Gakkai Zasshi (J Jpn Ophthalmol Soc) 126: 948-957,2022.