HSV-1 is an infectious pathogen that widely infects humans, normally, it exists in the human body in a latent state., When it becomes active, it may cause many diseases such as cold sores, herpetic keratitis, neonatal herpes and encephalitis. An important feature of HSV-1 is that after infection of peripheral tissues, it enters neurons to undergo latent infection, thereby evading host immunity. When the host is immunocompromised or under stress, the latent virus reactivate to undergo recurrent infection. Latency and reactivation are the key reasons why HSV-1 can spread and cause disease in the presence of immunity and drugs.

To further explore the regulation of HSV-1, Dr. PAN Dongli from Zhejiang University School of Basic Medical Sciences/ Affiliated Sir Run Run Shaw Hospital published a research paper in Nature Microbiology entitled Regulation of host and virus genes by neuronal miR-138 favours herpes simplex virus-1 latency.

Based on the discovery that neuro-specific microRNA (miR-138) can bind to the viral ICP0 transcript, the team found that in addition to targeting ICP0, miR-138 can also inhibit virus replication in cells and mice in an ICP0-independent manner. By combining multiple methods including RNA-seq, PAR-CLIP and siRNA, the team found that miR-138 can inhibit the expression of two host transcription factors OCT-1 and FOXC1, which are very important for HSV-1 replication. OCT-1 is a known host factor that can help HSV-1 to initiate transcription. FOXC1 is a new host regulatory factor discovered by the team.

Next, the research team found that FOXC1 can significantly promote HSV-1 replication in the mouseneuronal tissues and cells in vivo and in vitro. In terms of mechanisms, FOXC1 can not only promote viral gene transcription globally, but also reduce the level of heterochromatin bound to the HSV-1 genome, indicating that it can attenuate the cellular epigenetic gene silencing mechanisms. Interestingly, studies have shown that the viral ICP0 protein has a similar role in epigenetic regulation, and the research team found that FOXC1 can compensate for the replication defects of an ICP0-null mutant virus.

In this research, Dr. PAN’s team found that miR-138 that is specifically highly expressed in neuronal cells can simultaneously regulate the virus ICP0 gene and the host OCT-1 and FOXC1 genes, and these regulatory effects convergently inhibit the expression of viral lytic genes, thus creating favorable conditions for HSV-1 latency. 

Please refer to the original article for further information：https://www.nature.com/articles/s41564-020-00860-1