Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida, USA.
J Virol. 2023 Dec 21;97(12):e0143823. doi: 10.1128/jvi.01438-23. Epub 2023 Nov 22.
Herpes simplex virus 1 (HSV-1) establishes lifelong latency in neuronal cells. Following a stressor, the virus reactivates from latency, virus is shed at the periphery and recurrent disease can occur. During latency, the viral lncRNA termed the latency-associated transcript (LAT) is known to accumulate to high abundance. The LAT is known to impact many aspects of latency though the molecular events involved are not well understood. Here, we utilized a human neuronal cell line model of HSV latency and reactivation (LUHMES) to identify the molecular-binding partners of the LAT during latency. We found that the LAT binds to both the cellular protein, TMEM43, and HSV-1 genomes in LUHMES cells. Additionally, we find that knockdown of TMEM43 prior to infection results in a decreased ability of HSV-1 to establish latency. This work highlights a potential mechanism for how the LAT facilitates the establishment of HSV-1 latency in human neurons.
单纯疱疹病毒 1（HSV-1）在神经元细胞中建立终身潜伏。在应激源后，病毒从潜伏中重新激活，病毒在周围释放，可能会出现复发疾病。在潜伏期间，病毒长非编码 RNA 被称为潜伏相关转录物（LAT），其积累到高丰度。虽然涉及的分子事件尚未完全理解，但 LAT 已知会影响潜伏的许多方面。在这里，我们利用人类神经元细胞系 HSV 潜伏和再激活模型（LUHMES）来鉴定潜伏期间 LAT 的分子结合伴侣。我们发现 LAT 在 LUHMES 细胞中与细胞蛋白 TMEM43 和 HSV-1 基因组结合。此外，我们发现感染前敲低 TMEM43 会导致 HSV-1 建立潜伏的能力下降。这项工作强调了 LAT 促进 HSV-1 在人类神经元中建立潜伏的潜在机制。
